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1

Wang, Ningling, Ping Zhang, Xuejiang Guo, Zuomin Zhou, and Jiahao Sha. "Hnrnpk, a Protein Differentially Expressed in Immature Rat Ovarian Development, Is Required for Normal Primordial Follicle Assembly and Development." Endocrinology 152, no. 3 (March 1, 2011): 1024–35. http://dx.doi.org/10.1210/en.2010-0797.

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The formation of ovarian follicles and subsequent development after birth are critical processes for female reproduction, and inappropriate coordination of these processes contributes to ovarian pathologies, such as premature ovarian failure and infertility. Identification and functional investigation of the factors involved in follicular assembly and the initial recruitment will be of great significance to the understanding of the female reproduction process. In this study, we examined the roles of transcription factor heterogeneous nuclear ribonucleoprotein K (Hnrnpk) in rat primordial folliculogenesis using RNA interference knockdown strategies. Reducing Hnrnpk mRNA levels via Hnrnpk small interfering RNAs to neonatal ovaries resulted in a substantial loss of naked oocytes, primordial and primary follicles. Structure disorganization of the ovary characterized by groups of oocytes arranged in nests, clusters of somatic cells not associated with any oocytes and many highly condensed oocyte nuclei was observed. Terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling assay demonstrated that these abnormalities may be partially attributable to abnormal apoptosis of oocytes. Furthermore, the microarray analysis showed that 63 genes changed significantly (≥2-folds or ≤0.5-fold) between the ovaries treated with Hnrnpk small interfering RNAs and the controls, with 22 up-regulated genes and 41 down-regulated genes. These differentially expressed genes were involved in several critical biological processes in ovarian development. These results suggest that transcription factor Hnrnpk is a key regulator for primordial follicle assembly and development, which provides a new potential therapeutic target to regulate ovarian function and treat ovarian disease.
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2

Sofi, Fayaz A., Wasim Ahmed, Ghulam Nabi Dhobi, Showkat Ali Mufti, Rafi Ahmed Jan, Shaheen Nazir Lone, and Bashir Ahmad Shah. "A Early Development of Severe Ovarian Hyperstimulation Syndrome following Ovulation Induction." JMS SKIMS 14, no. 1 (June 11, 2011): 30–32. http://dx.doi.org/10.33883/jms.v14i1.70.

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Ovarian Hyperstimulation is a rare but potentially fatal complication of ovarian stimulation during treatment of infertility. Worldwide the incidence of this syndrome is increasing due to liberal use of invitro fertilization for management of infertility. The syndrome is characterized by cystic ovarian enlargement and abnormal capillary permeability due to secretion of vasogenic substances by ovaries. The syndrome is classified into early and late variants with early variants usually mild to moderate in severity. We present a case of severe ovarian hyperstimulation syndrome (OHSS) developing early in a 25-year female while undergoing In-vitro fertilization (IVF). Six days after ovulation induction, the woman developed ascites, bilateral pleural effusion and acute renal failure with ultrasound abdomen revealing bilateral cystic enlargement of ovaries. JMS 2011;14(1):30-32
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3

Dwi Sandhiutami, Ni Made, Puspita Eka Wuyung, Wawaimuli Arozal, Melva Louisa, and Deni Rahmat. "Ovarian Cancer Animal Models for Preclinical Studies and Development of Ovarian Cancer Drugs." JURNAL ILMU KEFARMASIAN INDONESIA 17, no. 2 (October 29, 2019): 139. http://dx.doi.org/10.35814/jifi.v17i2.734.

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Treatment for ovarian carcinoma is still far from optimal, animal models are still needed to study human epithelial ovarian cancer. Animal models of ovarian cancer are very important for understanding the pathogenesis of the disease and for testing new treatment strategies. Ovarian carcinogenesis models in mice have been modified and repaired to produce preneoplastic lesions and neoplastic ovaries that are pathogens resembling human ovarian cancer. Although spontaneous ovarian tumors in mice have been reported, some of the shortcomings of existing studies preclude their use as animal models of ovarian cancer. Because of this, many efforts have been made to develop animal models that are relevant for ovarian cancer. Experimental animal models are developed accurately to represent cellular and molecular changes associated with the initiation and development of human ovarian cancer. Accurate experimental models have significant potential in facilitating the development of better methods for early detection and treatment of ovarian cancer. Several animal models of ovarian cancer have been reported, including manipulation of various reproductive factors or exposure to carcinogens. The latest advance in ovarian cancer modeling is using genetically engineered mice.
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4

Lee, Hyun Ju, Janice M. Bahr, Pincas Bitterman, Sanjib Basu, Sameer Sharma, Jacques S. Abramowicz, and Animesh Barua. "Polycystic Ovarian Condition May Be a Risk Factor for Ovarian Tumor Development in the Laying Hen Model of Spontaneous Ovarian Cancer." Journal of Immunology Research 2018 (November 25, 2018): 1–13. http://dx.doi.org/10.1155/2018/2590910.

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Chronic inflammation and long-standing oxidative stress are potential predisposing factors for developing malignancies, including ovarian cancer (OVCA). Information on the association of ovarian chronic abnormal conditions, including polycystic ovarian syndrome (PCOS), with the development of OVCA is unknown. The goal of this study was to examine if polycystic ovarian conditions are associated with OVCA development. In the exploratory study, 3–4-year-old laying hens were randomly selected and examined for the presence of polycystic ovaries with cancer (PCOC). In the prospective study, hens were monitored by ultrasound scanning to detect the incidence of a polycystic ovaries and subsequent development of OVCA. Tissues from normal ovaries and PCOC were examined for macrophage infiltration, expression of interleukin-16, and superoxide dismutase 2. The exploratory study detected spontaneous PCOC at early and late stages in hens. PCOC in hens were accompanied with influx of macrophages (17.33 ± 2.26 in PCOC at the early stage and 24.24 ± 2.5 in PCOC at the late stage in 20 mm2 areas of tissue as compared with 6.77 ± 1.58 in normal hens). Expression of interleukin-16 was more than 2.5-fold higher and superoxide dismutase 2 was approximately 3-fold higher in PCOC hens than normal hens. The prospective study showed the development of OVCA in some hens with polycystic ovarian condition (PCO). PCOC development in hens was associated with chronic inflammation in the ovary. Laying hens may represent a potential model for the study of spontaneous PCOS and its long-term risk of PCOC development.
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5

Segino, Miwa, Mario Ikeda, Fumiki Hirahara, and Kahei Sato. "In vitro follicular development of cryopreserved mouse ovarian tissue." Reproduction 130, no. 2 (August 2005): 187–92. http://dx.doi.org/10.1530/rep.1.00515.

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In a previous report, we showed that follicles isolated from frozen/thawed mouse ovarian tissues reached the mature follicle stage on the 12th day of culture. However, the developmental ability was lower than that of fresh ovarian tissue. The purpose of this study was to define a culture system with some technical modification for preantral follicles isolated from frozen/thawed ovarian tissue and to confirm cell injury. Ovaries obtained from three-week-old female mice were cryopreserved by the rapid freezing method. Preantral follicles isolated from frozen/thawed ovarian tissues were cultured for 12–16 days. The follicles were then stimulated with human chorionic gonadotropin. In vitro fertilization was performed on the released cumulus–oocyte complexes (COCs). Preantral follicle viability was assessed by supravital staining using Hoechst 33258. Using this stain cell death was found in part of the granulosa cells of a follicle obtained from frozen/thawed ovarian tissue. On the 14th and 16th days of culture, the diameters of follicles isolated from frozen/thawed ovaries were larger than on the 12th day of culture. The released COCs were fertilized and developed to the blastocyst stage in 15.8% (12/76) of the oocytes taken from the fresh group, and in 0% (0/73), 2.9% (2/69) and 19.1% (22/115) of the oocytes taken from the frozen/thawed group that had been cultured for 12, 14 and 16 days respectively. The preantral follicles isolated from frozen/thawed mouse ovarian tissues developed slowly compared with the freshly prepared preantral follicles. During prolonged culture from 12 to 16 days, these follicles obtained the potential to fertilize and develop to the blastocyst stage.
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6

Cossigny (Rosairo), D. A., J. K. Findlay, and A. E. Drummond. "123. ACTIVIN A AND OVARIAN FOLLICLE DEVELOPMENT." Reproduction, Fertility and Development 21, no. 9 (2009): 42. http://dx.doi.org/10.1071/srb09abs123.

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A significant developmental stage in ovarian folliculogenesis is the acquisition of gonadotropin sensitivity by ovarian follicles. Activin has previously been suggested to be involved in the responsiveness of granulosa cells to FSH (1). Therefore, the role of activin was investigated using a ‘physiological’ culture system to determine if pathways exist to transduce activin signals within the postnatal rat ovary. Organ cultures with day 4 whole ovaries were employed in order to assess the potential impact of Activin A on follicle growth and transition from the primordial through to the primary and later preantral stages of development. Ovaries were isolated and cultured for 10 days with the addition of supplemented DMEM/Hams F-12 media (2)and either FSH (100ng/ml), Activin A (50ng/ml), or a combination of the two. Media and treatments were refreshed every alternate day. At the end of the culture period, ovaries were fixed and sectioned, or placed immediately into Ultraspec for RNA extraction for future real-time PCR. Sections were used for morphological assessment and ovarian follicle counting of primordial, primary and preantral follicles. An evaluation of atresia by the detection of apoptotic cells was undertaken using terminal deoxynucleotidyl transferase (TdT) mediated dUTP-biotin nick-end labeling (TUNEL). Primary follicle numbers increased significantly (P<0.05) in the combined treatment group whereas, preantral follicle numbers increased significantly (P<0.0001) when treated with Activin A alone. This is consistent with a morphological appraisal of atresia where a decrease in atresia was found in primordial and primary follicles, supporting the primary follicle development data and Activin A treatment alone resulted in more healthy primary and preantral follicles than atretic ones. Therefore, a stimulatory role for Activin A both in the presence of FSH (primary follicle development) or alone (preantral follicle development) has resulted in more follicles making the transition from the primordial to primary stages, as well as to the later preantral stages.
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7

Sato, Yorino, Yuan Cheng, Kazuhiro Kawamura, Seido Takae, and Aaron J. W. Hsueh. "C-Type Natriuretic Peptide Stimulates Ovarian Follicle Development." Molecular Endocrinology 26, no. 7 (July 1, 2012): 1158–66. http://dx.doi.org/10.1210/me.2012-1027.

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Abstract C-type natriuretic peptide (CNP) encoded by the NPPC (Natriuretic Peptide Precursor C) gene expressed in ovarian granulosa cells inhibits oocyte maturation by activating the natriuretic peptide receptor (NPR)B (NPRB) in cumulus cells. RT-PCR analyses indicated increased NPPC and NPRB expression during ovarian development and follicle growth, associated with increases in ovarian CNP peptides in mice. In cultured somatic cells from infantile ovaries and granulosa cells from prepubertal animals, treatment with CNP stimulated cGMP production. Also, treatment of cultured preantral follicles with CNP stimulated follicle growth whereas treatment of cultured ovarian explants from infantile mice with CNP, similar to FSH, increased ovarian weight gain that was associated with the development of primary and early secondary follicles to the late secondary stage. Of interest, treatment with FSH increased levels of NPPC, but not NPRB, transcripts in ovarian explants. In vivo studies further indicated that daily injections of infantile mice with CNP for 4 d promoted ovarian growth, allowing successful ovulation induction by gonadotropins. In prepubertal mice, CNP treatment alone also promoted early antral follicle growth to the preovulatory stage, leading to efficient ovulation induction by LH/human chorionic gonadotropin. Mature oocytes retrieved after CNP treatment could be fertilized in vitro and developed into blastocysts, allowing the delivery of viable offspring. Thus, CNP secreted by growing follicles is capable of stimulating preantral and antral follicle growth. In place of FSH, CNP treatment could provide an alternative therapy for female infertility.
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8

Chellappa, S., M. R. Câmara, and J. R. Verani. "Ovarian development in the Amazonian red discus, Symphysodon discus Heckel (Osteichthyes: Cichlidae)." Brazilian Journal of Biology 65, no. 4 (November 2005): 609–16. http://dx.doi.org/10.1590/s1519-69842005000400007.

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The Neotropical red discus fish, Symphysodon discus, originates from the Amazonian basin and has a discoid body. Although this species is popularly used in aquaria and is exported as an ornamental fish, it has not been intensively studied. The purpose of this work was to study the morphological and histological aspects of the ovarian development in the red discus. Forty females of S. discus of varying body sizes and different stages of gonadal development were used in this study. The ovaries were weighed and examined macroscopically in order to observe the maturation stages. Histological staining of hematoxilin-eosin was used for microscopic observations of the ovaries. Macroscopic observations showed immature, maturing, mature and partially spent stages of ovarian development. Microscopic examination of the ovaries revealed five stages and five phases of ovarian development. The ovaries of the mature females showed all the different phases of oocyte development, indicating the multiple spawning habit of this species.
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9

Sobinoff, A. P., V. Pye, B. Nixon, S. D. Roman, and E. A. McLaughlin. "153. XENOBIOTICS; INFLUENCE ON OVARIAN FOLLICULAR DEVELOPMENT." Reproduction, Fertility and Development 21, no. 9 (2009): 71. http://dx.doi.org/10.1071/srb09abs153.

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The mammalian female reproductive lifespan is largely defined by a finite pool of ovarian follicles established around the time of birth. It is now understood that certain synthetic chemical compounds, known as xenobiotics, can cause premature ovarian senescence through the destruction of small ovarian follicles. Although the ovotoxic effects of these chemicals are well documented, the exact molecular mechanisms behind their action are only just becoming understood. Recent evidence suggests that bioactivation of xenobiotics by Phase I detoxifying enzymes may lead to the generation of free oxygen radicals (ROS), which we suspect may perturb intracellular signalling pathways in primordial follicles. In this study we attempted to identify ovarian follicle signalling pathways activated by xenobiotic exposure using ovotoxic agents which target immature follicles. Neonatal ovaries obtained from 3/4-day old Swiss mice were exposed to either 4-Vinylcyclohexene (25µM), Methoxychlor (25µM) or Menadione (5µM) for 96hrs using our in vitro culture system. Total RNA was then collected and analysed using Affymetrix Mouse Genome 430 2.0 Arrays. Bioinformatic analysis identified between ~500–1000 genes with a two-fold significant difference in gene expression (p<0.05) for each xenobiotic compared to the control. Differentially expressed genes were analysed for pathways and molecular functions using Ingenuity Pathways Analysis (Ingenuity Systems). In agreement with the current literature, many of the genes belonged to toxic response pathways, such as; Xenobiotic metabolism (10); p53 (15) and Apoptosis (11) signalling. However, the vast majority of the differentially expressed genes belonged to canonical pathways implicated in follicular development, such as PI3K/AKT (18), Wnt/ b -catenin (21), and JAK/Stat (8) signalling. Further qPCR analysis has confirmed a substantial increase in the transcription factor Sox4 and cell cycle inhibitor Cdkn2a in 4-Vinylcyclohexene and Menadione treated ovaries respectively. These results suggest that xenobiotics which target primordial follicles may exert part of their ovotoxic effects by perturbing signalling pathways involved in follicular activation and development.
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10

Prokopuk, Lexie, Ellen G. Jarred, Rheannon O. Blücher, Eileen A. McLaughlin, Jessica M. Stringer, and Patrick S. Western. "An essential role for Polycomb Repressive Complex 2 in the mouse ovary." Reproduction 163, no. 3 (March 1, 2022): 167–82. http://dx.doi.org/10.1530/rep-21-0361.

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Polycomb repressive complex 2 (PRC2) catalyses the repressive epigenetic modification of histone 3 lysine 27 tri-methylation (H3K27me3) and functions as a key epigenetic regulator during embryonic development. PRC2 is known to regulate the development of a range of tissues by transcriptional silencing of genes that control cell differentiation, but its roles in female germline and ovarian development remain unknown. Using a mouse model with hypomorphic embryonic ectoderm development (EED) function that reduced H3K27me3 in somatic and germ cells, we found that PRC2 was required for survival, with more than 95% of female animals dying before birth. Although surviving adult EED hypomorphic females appeared morphologically similar to controls and were fertile, Eedhypo/hypo adult ovaries were abnormal, with altered morphology characterised by abnormal follicles. Early Eedhypo/hypo and control fetal ovaries were morphologically similar, and germ cells entered meiosis normally. Immunofluorescent analyses of somatic and germline markers indicated that ovarian development in Eedhypo/hypo ovaries was similar to heterozygous and WT controls. However, TUNEL analyses revealed higher rates of apoptosis in the ovarian surface epithelium, and transcriptional analyses revealed changes in genes regulating epithelial and steroidogenic cell differentiation, possibly foreshadowing the defects observed in adult ovaries of hypomorphic females. While it was possible to analyse early-mid fetal ovarian development, postnatal stages were inaccessible due to the high level of lethality during late fetal stages. Despite this limitation, the data we were able to obtain reveal a novel role for EED in the ovary that is likely to alter ovarian development and ovarian function in adult animals.
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11

Bridges, Kamiya, Humphrey H. C. Yao, and Barbara Nicol. "Loss of Runx1 Induces Granulosa Cell Defects and Development of Ovarian Tumors in the Mouse." International Journal of Molecular Sciences 23, no. 22 (November 21, 2022): 14442. http://dx.doi.org/10.3390/ijms232214442.

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Genetic alterations of the RUNX1 gene are associated with a variety of malignancies, including female-related cancers. The role of RUNX1 as either a tumor suppressor gene or an oncogene is tissue-dependent and varies based on the cancer type. Both the amplification and deletion of the RUNX1 gene have been associated with ovarian cancer in humans. In this study, we investigated the effects of Runx1 loss on ovarian pathogenesis in mice. A conditional loss of Runx1 in the somatic cells of the ovary led to an increased prevalence of ovarian tumors in aged mice. By the age of 15 months, 27% of Runx1 knockout (KO) females developed ovarian tumors that presented characteristics of granulosa cell tumors. While ovaries from young adult mice did not display tumors, they all contained abnormal follicle-like lesions. The granulosa cells composing these follicle-like lesions were quiescent, displayed defects in differentiation and were organized in a rosette-like pattern. The RNA-sequencing analysis further revealed differentially expressed genes in Runx1 KO ovaries, including genes involved in metaplasia, ovarian cancer, epithelial cell development, tight junctions, cell−cell adhesion, and the Wnt/beta-catenin pathway. Together, this study showed that Runx1 is required for normal granulosa cell differentiation and prevention of ovarian tumor development in mice.
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12

Rosairo, D. A., J. K. Findlay, and A. E. Drummond. "270. TGF-β and ovarian follicle development." Reproduction, Fertility and Development 20, no. 9 (2008): 70. http://dx.doi.org/10.1071/srb08abs270.

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The role TGF-β plays in ovarian follicular growth and differentiation was investigated using a ‘physiological' culture system. TGF- β ligand and receptors are present in the rat ovary from 4 days after birth. Therefore we established organ cultures with these ovaries in order to assess the potential impact of TGF- β1 on follicle growth and transition from the primordial through to the primary and preantral stages of development. Whole ovaries were isolated and cultured for 10 days on floating filters with the addition of supplemented DMEM/Hams F-12 media and either FSH (100ng/mL), TGF- β1 (10ng/mL), or a combination of the two. Media as well as treatments were refreshed every second day. At the end of the culture period, ovaries were fixed in 10% formalin, embedded in paraffin and sectioned at 5µm. Sections were used for morphological assessment and ovarian follicle counting with three serial sections mounted/slide and every alternate slide used for counting of primordial, primary and preantral follicles. An evaluation of atresia by the detection of apoptotic cells was undertaken using terminal deoxynucleotidyl transferase (TdT) mediated dUTP-biotin nick-end labelling (TUNEL) via the ApopTag® Peroxidase in situ apoptosis detection kit. Results gathered from this study show preantral follicle numbers declined significantly when treated with the combination of FSH and TGF- β1, consistent with our morphological appraisal of atresia where the combined treatment appeared to produce more apoptotic follicles than healthy follicles, suggesting an increase in atretic primary and preantral follicles. These preliminary findings suggest an inhibitory role for TGF- β1 in the presence of FSH, resulting in fewer follicles making the transition from the primary to the preantral stage. Further studies are required to test the effects of other TGF-β superfamily members on follicle transition in vitro. Supported by the NHMRC of Australia (Regkeys 241000, 441101, 465415, 198705)
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13

Kobayashi, Hiroshi, Kazuhiro Sumimoto, Takashi Kitanaka, Yoshihiko Yamada, Toshiyuki Sado, Mariko Sakata, Shozo Yoshida, et al. "Ovarian endometrioma—Risks factors of ovarian cancer development." European Journal of Obstetrics & Gynecology and Reproductive Biology 138, no. 2 (June 2008): 187–93. http://dx.doi.org/10.1016/j.ejogrb.2007.06.017.

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14

Brown, Hannah M., Rebecca L. Robker, and Darryl L. Russell. "Development and Hormonal Regulation of the Ovarian Lymphatic Vasculature." Endocrinology 151, no. 11 (September 15, 2010): 5446–55. http://dx.doi.org/10.1210/en.2010-0629.

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The lymphatic vasculature plays a number of essential physiological roles including maintaining fluid homeostasis, providing a network for the transport of immune cells, and facilitating the uptake of fat-soluble nutrients from the gastrointestinal tract. Although the critical importance and remodeling capacity of the blood vasculature has been well described within the ovary, just a few reports describe the lymphatic vasculature. Using histological and molecular techniques, we report the kinetics of ovarian lymphangiogenesis and the hormonal regulation of lymphangiogenic growth factors associated with key stages of ovarian follicle growth. We exploited the Adamts1-null mouse model, a model with a previously characterized lymphatic defect to further interrogate the mechanisms controlling ovarian lymphangiogenesis. The establishment and development of the ovarian lymphatic vascular network in postnatal developing ovaries was associated with the presence and hormonal regulation of the lymphangiogenic growth factors and their receptors, including Vegfc, Vegfd, and Vegfr3. We characterized the hormonally regulated remodeling of the ovarian lymphatic vasculature in response to FSH and estradiol. The lymphatic network was defective in the Adamts1-null ovary, clearly demonstrating both the involvement of FSH/estradiol and the Adamts1 (a disintegrin and metalloproteinase with thrombospondin motifs 1) protease in ovarian lymphangiogenesis. This study provides the first evidence of a malleable lymphatic system responsive to hormonal changes of the female reproductive cycle, at least in the mouse ovary, suggesting a role for lymphatic vessel functions in normal folliculogenesis.
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15

Zhang, W., N. Gan, and J. Zhou. "Immunohistochemical Investigation of the Correlation between LIM Kinase 1 Expression and Development and Progression of Human Ovarian Carcinoma." Journal of International Medical Research 40, no. 3 (June 2012): 1067–73. http://dx.doi.org/10.1177/147323001204000325.

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OBJECTIVES: LIM kinase 1 (LIMK1) is implicated in cellular mechanisms regulating tumour cell invasion and may be involved in ovarian carcinoma progression. This retrospective study, therefore, investigated expression of the LIMK1 gene in primary ovarian tumour tissue samples and evaluated the correlation between LIMK1 gene expression and progression of ovarian carcinoma. METHODS: LIMK1 protein levels were detected by immunohistochemistry in ovarian tissue samples from 57 patients with primary ovarian epithelial tumours (benign, n = 13; borderline, n = 14; carcinoma, n = 30) and 10 patients with normal ovaries. LIMK1 protein levels were evaluated by calculating the product of the scores for stain intensity and percentage of cells stained. RESULTS: There was a significant correlation between increasing LIMK1 protein levels and increasing disease severity, from normal ovarian tissues through benign and borderline tumours to ovarian carcinoma. There was also a significant correlation between increasing LIMK1 protein levels and increasingly poor levels of differentiation of ovarian carcinoma. CONCLUSIONS: LIMK1 is associated with the development of ovarian cancer and with the level of tumour differentiation in patients with ovarian carcinoma.
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Wu, Xugan, Meimei Liu, Jie Pan, Hao Chen, Chaoshu Zeng, and Yongxu Cheng. "The ovarian development pattern of pond-reared Chinese mitten crab, Eriocheir sinensis H. Milne-Edwards, 1853." Crustaceana 90, no. 4 (2017): 449–70. http://dx.doi.org/10.1163/15685403-00003662.

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Although pond culture is the major culture method for Chinese mitten crab (Eriocheir sinensis) in China, the pattern of ovarian development in pond-rearedE. sinensisremains unclear. This study investigated the changes in ovarian morphology and histology, gonadosomatic index (GSI), hepatosomatic index (HSI), and monthly variation of the ovarian development pattern during the ovarian maturation of pond-reared femaleE. sinensis. Based on the pubertal moult, and ovarian morphology and histology, the ovarian development cycle ofE. sinensiscould be divided into five stages, i.e., Stage I: the ovary appears thin ribbon-like and translucent, dominated by oogonia (OG) and previtellogenic oocytes (PRO); Stage II: the ovary appears milk white or buff, dominated by endogenous vitellogenic oocytes (EN); Stage III: the ovary appears orange or light brown, dominated by exogenous vitellogenic oocytes (EX); Stage IV: the ovary appears crimson red or brown and ovarian lobes occupy most available body cavities. The major oocytes were nearly mature oocytes (NO); Stage V: the ovary appears deep purple and is filled with mature oocytes (MO). During ovarian maturation, the GSI increased significantly and a significant, positive correlation was found between the GSI and the mean long diameter of the oocyte from stage III to stage V. However, a significantly negative correlation was found between GSI and HSI. The ovarian development of pond-reared femaleE. sinensiswas not synchronous, most of the pubertal moults were found until mid-late August. At the end of August, the percentages of females that reached ovarian stages II and III were 55 and 24%, respectively. After that, the ovarian development of pond-reared femaleE. sinensisbecame fast, and females with stage III or more advanced ovaries were found to be in excess of 80% by the end of September and onward. From the end of November to late December, the GSI of femaleE. sinensisdid not increase significantly, which indicated pond-reared females had reached mature or nearly-mature ovaries by the end of November.
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Pattiasina, Betsy J., M. Zairin Junior, I. Mokoginta, R. Affandi, and W. Manalu. "Ovarian development of female mud crab, Scylla serrata supplemented with cholesterol and injected with serotonin." Jurnal Akuakultur Indonesia 9, no. 1 (January 1, 2010): 67. http://dx.doi.org/10.19027/jai.9.67-76.

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<p>Cholesterol is known to play an important role in nutrition of crustacean and function as a precursor for steroids synthesis, while neurohormone of serotonin could induce ovarian maturation in crustacean. Ovarian development of adult females <em>Scylla serrata </em>was induced by adding cholesterol in the diet and serotonin injection. This research was designed to study the effectiveness of cholesterol supplementation and serotonin injection in ovarian development. Broodstocks were stocked in nine experimental units in three fiber tanks. The fiber tank was equipped with sands substrate and flow through seawater system. The experimental crabs were assigned into a completely randomized design with a 3 x 3 factorial arrangement. The first factor was cholesterol supplementation in the diet with 3 levels (0, 0,5 and 1,0%). The second factor was serotonin injection with 3 levels (0, 5 and 10 μg/g BW). Samples of broodstock were taken every four days to evaluate the stages of ovarian maturity and parameters were used to evaluate the ovarian maturation stage are gonad index (GI) and oocyte diameter, concentration of estradiol 17β, <em>yolk</em> protein concentrations, and fecundity. Results showed that female crabs supplemented with 0,5% cholesterol and a combination of cholesterol 0,5% supplementation and injection serotonin with a dose of 10 μg/g BW had better reproduction development. It is concluded that ovarian development of <em>Scylla serrata </em>could be improved by cholesterol supplementation and serotonin injection.</p> <p>Key words: Cholesterol, serotonin, ovarian development, <em>Scylla serrata</em></p> <p> </p> <p>ABSTRAK</p> <p>Kolesterol diketahui merupakan nutrien spesifik yang berperan dalam sisntesis hormon steroid dan mengontrol reproduksi, sementara serotonin merupakan salah satu neurohormon yang dilaporkan dapat merangsang pematangan ovari dan pemijahan pada krustase. Penelitian ini bertujuan untuk mengetahui pengaruh tingkat pemberian kolesterol yang optimal dalam pakan buatan, serta dosis penyuntikan serotonin yang efektif untuk mempercepat proses perkembangan dan pematangan ovarium induk kepiting bakau <em>Scylla serrata</em>. Pemeliharaan induk dilakukan dengan menggunakan tiga buah bak fiber. Bak pemeliharaan dilengkapi dengan substrat pasir dan sistim air laut mengalir. Eksperimen menggunakan rancangan acak lengkap (RAL) pola faktorial, dengan 9 satuan percobaan. Faktor pertama, suplemen kolesterol didalam pakan dengan 3 tingkat dosis (0; 0,5; dan 1%) dan faktor kedua, injeksi serotonin dengan 3 tingkat dosis (0, 5, dan <a name="OLE_LINK1">10 </a>μg/g bobot tubuh). Pengamatan terhadap tingkat kematangan ovari dilakukan setiap 4 hari sekali. Paramater pengambilan sampel meliputi tingkat kematangan ovari, indeks gonad dan diameter oosit, konsentrasi estradiol 17β, konsentrasi protein <em>yolk</em>, dan fekunditas. Hasil penelitian menunjukkan bahwa induk kepiting yang disuplementasi dengan dosis kolesterol 0,5% dan induk kepiting yang mendapat perlakuan kombinasi, suplementasi kolesterol 0,5% dan injeksi serotonin dosis 10 μg/g bobot tubuh dapat menghasilkan perkembangan ovari yang terbaik. Jadi kolesterol dan serotonin dapat digunakan untuk meningkatkan perkembangan ovari.</p> <p>Kata-kata kunci: Kolesterol, serotonin, perkembangan ovari, <em>Scylla serrata</em></p>
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Rasmussen, Tina H., Thomas K. Andreassen, Søren N. Pedersen, Leo T. M. Van der Ven, Poul Bjerregaard, and Bodil Korsgaard. "Effects of waterborne exposure of octylphenol and oestrogen on pregnant viviparous eelpout (Zoarces viviparus) and her embryos in ovario." Journal of Experimental Biology 205, no. 24 (December 15, 2002): 3857–76. http://dx.doi.org/10.1242/jeb.205.24.3857.

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SUMMARY Exposure to oestrogenic chemicals (xeno-oestrogens) may have severe effects on embryonic development. The present study investigates whether the oestrogenic endocrine disruptor 4-tert-octylphenol (4-tOP) or 17β-oestradiol (E2) is accumulated in the viviparous fish the eelpout (Zoarces viviparus) and transferred to the embryos in ovario and subsequently affects embryonic development, including gonadal differentiation. Pregnant eelpouts were exposed to nominal concentrations of 25 μgl-1 or 100 μgl-1 4-tOP (OP25 or OP100,respectively) or 0.5 μgl-1 E2 in water. During 4-tOP exposure, the compound accumulated in both plasma and ovarian fluid in a concentration-dependent manner. In the mother fish, the oestrogenic biomarkers, vitellogenin (Vtg) in plasma, Vtg mRNA in liver and oestrogen-binding activity in liver, were all induced by 4-tOP (and by E2) at an actual concentration of 14 μgl-1. E2 and 4-tOP were examined for their potency to disturb the maternal—foetal trophic relationship by disturbing the physiology of the ovary and by changing the distribution of essential nutrients normally transported to embryos during pregnancy. After exposure to E2 or 4-tOP, calcium was depleted from the ovarian fluid and the level of free amino acids available in maternal plasma was decreased. A marked overall effect on ovarian components, including the ovarian sac, ovarian fluid and embryonic mass, was evident. Embryonic growth was significantly decreased, which might in part be attributed to disturbances of the maternal—foetal trophic relationship. Marked inductions of Vtg mRNA and Vtg protein, determined by RT-PCR and immunohistochemistry, respectively, were found in embryos from the OP100 group — the only group to show considerable accumulation of an oestrogenic compound in the ovarian fluid. A different pattern of gonadal development was found in embryos from the OP100 group compared with embryos from the control, OP25 or E2 groups, in which approximately 50% had normal ovaries and 50% had normal presmptive male gonads. In the OP100 group,46% had normal ovaries but, in contrast to controls, only 22% had normal presumptive male gonads, whereas the remaining 32% had abnormal male gonads with structures resembling the endo-ovarian cavity of a female gonad. As oestrogen receptor (ER) expression was detected by in situhybridisation in early differentiating gonads, these effects could be mediated by direct interaction of the xeno-oestrogens with gonadal ER. In conclusion,this study indicates that the xeno-oestrogen 4-tOP can be transferred from the water via the mother fish to the ovarian fluid and can subsequently disturb the maternal—foetal trophic relationship and cause severe effects on embryonic development, including gonadal differentiation in ovario.
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19

Jo, Misung, Mary C. Gieske, Charles E. Payne, Sarah E. Wheeler-Price, Joseph B. Gieske, Ignatius V. Ignatius, Thomas E. Curry, and CheMyong Ko. "Development and Application of a Rat Ovarian Gene Expression Database." Endocrinology 145, no. 11 (November 1, 2004): 5384–96. http://dx.doi.org/10.1210/en.2004-0407.

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Abstract The pituitary gonadotropins play a key role in follicular development and ovulation through the induction of specific genes. To identify these genes, we have constructed a genome-wide rat ovarian gene expression database (rOGED). The database was constructed from total RNA isolated from intact ovaries, granulosa cells, or residual ovarian tissues collected from immature pregnant mare serum gonadotropin (PMSG)/human chorionic gonadotropin-treated rats at 0 h (no PMSG), 12 h, and 48 h post PMSG, as well as 6 and 12 h post human chorionic gonadotropin. The total RNA was used for DNA microarray analysis using Affymetrix Rat Expression Arrays 230A and 230B (Affymetrix, Santa Clara, CA). The microarray data were compiled and used for display of individual gene expression profiles through specially developed software. The final rOGED provides immediate analysis of temporal gene expression profiles for over 28,000 genes in intact ovaries, granulosa cells, and residual ovarian tissue during follicular growth and the preovulatory period. The accuracy of the rOGED was validated against the gene profiles for over 20 known genes. The utility of the rOGED was demonstrated by identifying six genes that have not been described in the rat periovulatory ovary. The mRNA expression patterns and cellular localization for each of these six genes (estrogen sulfotransferase, synaptosomal-associated protein 25 kDa, runt-related transcription factor, calgranulin B, α1-macroglobulin, and MAPK phosphotase-3) were confirmed by Northern blot analyses and in situ hybridization, respectively. The current findings demonstrate that the rOGED can be used as an instant reference for ovarian gene expression profiles, as well as a reliable resource for identifying important yet, to date, unknown ovarian genes.
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20

Nwachukwu, Chinwe U., Kathryn J. Woad, Nicole Barnes, David S. Gardner, and Robert S. Robinson. "Maternal protein restriction affects fetal ovary development in sheep." Reproduction and Fertility 2, no. 2 (June 17, 2021): 161–71. http://dx.doi.org/10.1530/raf-20-0073.

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Maternal malnutrition has important developmental consequences for the foetus. Indeed, adverse fetal ovarian development could have lifelong impact, with potentially reduced ovarian reserve and fertility of the offspring. This study investigated the effect of maternal protein restriction on germ cell and blood vessel development in the fetal sheep ovary. Ewes were fed control (n = 7) or low protein (n = 8) diets (17.0 g vs 8.7 g crude protein/MJ metabolizable energy) from conception to day 65 of gestation (gd65). On gd65, fetal ovaries were subjected to histological and immunohistochemical analysis to quantify germ cells (OCT4, VASA, DAZL), proliferation (Ki67), apoptosis (caspase 3) and vascularisation (CD31). Protein restriction reduced the fetal ovary weight (P < 0.05) but had no effect on fetal weight (P > 0.05). The density of germ cells was unaffected by maternal diet (P > 0.05). In the ovarian cortex, OCT4+ve cells were more abundant than DAZL+ve (P < 0.001) and VASA+ve cells (P < 0.001). The numbers, density and estimated total weight of OCT4, DAZL, and VASA+ve cells within the ovigerous cords were similar in both dietary groups (P > 0.05). Similarly, maternal protein restriction had no effect on germ cell proliferation or apoptotic indices (P > 0.05) and the number, area and perimeter of medullary blood vessels and degree of microvascularisation in the cortex (P > 0.05). In conclusion, maternal protein restriction decreased ovarian weight despite not affecting germ cell developmental progress, proliferation, apoptosis, or ovarian vascularity. This suggests that reduced maternal protein has the potential to regulate ovarian development in the offspring. Lay summary Variations in a mother’s diet during pregnancy can influence her offspring’s growth and might cause fertility problems in the offspring in later life. We investigated whether reducing the protein fed to sheep during early pregnancy affects their daughters’ ovaries. We then compared our findings to the offspring of sheep on a complete diet. We measured ovary size and estimated the number of germ cells (cells that become eggs) they contained. We used cell markers to assess potential changes in the pattern of germ cell growth, division, and death, and how the ovarian blood supply had developed. We found that protein restriction reduced ovary size. However, the pattern of germ cell development, growth, or death was not altered by poor diet and blood vessels were also unaffected. This suggests that maternal diet can change ovarian development by an unknown mechanism and might reduce future fertility in their offspring.
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21

Smith, Peter, Dagmar Wilhelm, and Raymond J. Rodgers. "Development of mammalian ovary." Journal of Endocrinology 221, no. 3 (April 16, 2014): R145—R161. http://dx.doi.org/10.1530/joe-14-0062.

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Pre-natal and early post-natal ovarian development has become a field of increasing importance over recent years. The full effects of perturbations of ovarian development on adult fertility, through environmental changes or genetic anomalies, are only now being truly appreciated. Mitigation of these perturbations requires an understanding of the processes involved in the development of the ovary. Herein, we review some recent findings from mice, sheep, and cattle on the key events involved in ovarian development. We discuss the key process of germ cell migration, ovigerous cord formation, meiosis, and follicle formation and activation. We also review the key contributions of mesonephric cells to ovarian development and propose roles for these cells. Finally, we discuss polycystic ovary syndrome, premature ovarian failure, and pre-natal undernutrition; three key areas in which perturbations to ovarian development appear to have major effects on post-natal fertility.
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22

Cardenas, Carlos, Ayesha B. Alvero, Bo Seong Yun, and Gil Mor. "Redefining the origin and evolution of ovarian cancer: a hormonal connection." Endocrine-Related Cancer 23, no. 9 (September 2016): R411—R422. http://dx.doi.org/10.1530/erc-16-0209.

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Ovarian cancer has the highest mortality of all female reproductive cancers. Late diagnosis, tumour heterogeneity and the development of chemoresistance contribute to this statistic and work against patient survival. Current studies have revealed novel concepts that impact our view on how ovarian cancer develops. The greatest impact is on our understanding that, as a disease, ovarian cancer has multiple cellular origins and that these malignant precursors are mostly derived from outside of the ovaries. In this review, we propose a new concept of a step-wise developmental process that may underwrite ovarian tumorigenesis and progression: (1) migration/recruitment to the ovaries; (2) seeding and establishment in the ovaries; (3) induction of a dormant cancer stage; and (4) expansion and tumor progression. We will discuss the relationship of each step with the changing ovarian function and milieu during the reproductive age and the subsequent occurrence of menopause. The realization that ovarian cancer development and progression occurs in distinct steps is critical for the search of adequate markers for early detection that will offer personalized strategies for prevention and therapy.
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23

Chadwick, E. Michael P., Ross R. Claytor, Claude E. Léger, and Richard L. Saunders. "Inverse Correlation between Ovarian Development of Atlantic Salmon (Salmo salar) Smolts and Sea Age." Canadian Journal of Fisheries and Aquatic Sciences 44, no. 7 (July 1, 1987): 1320–25. http://dx.doi.org/10.1139/f87-156.

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In order to understand the factors which determine sea age of Atlantic salmon (Salmo salar), ovarian development of smolts was examined in 14 groups which varied in parental sea age, smolt age, and size. Parental sea age of smolts explained most of the variation in ovarian development. Smolts from one-sea-winter parents had a higher percentage of the more advanced oocyte stages in their ovaries, while smolts from two-sea-winter parents had a low percentage, and those from three-sea-winter parents had none. Annual within-stock variation and covariance with freshwater age were not significant. Hatchery-reared smolts had similar ovarian development to their wild counterparts. There was also a significant, positive correlation between fork length of smolts and ovarian development within groups.
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24

McFee, Renee M., and Andrea S. Cupp. "Vascular contributions to early ovarian development: potential roles of VEGFA isoforms." Reproduction, Fertility and Development 25, no. 2 (2013): 333. http://dx.doi.org/10.1071/rd12134.

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Vascularisation is an essential component of ovarian morphogenesis; however, little is known regarding factors regulating the establishment of vasculature in the ovary. Angiogenesis involving extensive endothelial cell migration is a critical component of vessel formation in the embryonic testis but vasculogenic mechanisms appear to play a prominent role in ovarian vascularisation. Vasculature has a strong influence on the formation of ovarian structures, and the early developmental processes of ovigerous cord formation, primordial follicle assembly and follicle activation are all initiated in regions of the ovary that are in close association with the highly vascular medulla. The principal angiogenic factor, vascular endothelial growth factor A (VEGFA), has an important role in both endothelial cell differentiation and vascular pattern development. Expression of VEGFA has been localised to ovigerous cords and follicles in developing ovaries and an increased expression of pro-angiogenic Vegfa isoform mRNA in relation to anti-angiogenic isoform mRNA occurs at the same time-point as the peak of primordial follicle assembly in perinatal rats. Elucidation of specific genes that affect vascular development within the ovary may be critical for determining not only the normal mechanisms of ovarian morphogenesis, but also for understanding certain ovarian reproductive disorders.
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25

Wei, Li, Meng, Zhang, Shen, and Liu. "Corticosterone Injection Impairs Follicular Development, Ovulation and Steroidogenesis Capacity in Mice Ovary." Animals 9, no. 12 (November 29, 2019): 1047. http://dx.doi.org/10.3390/ani9121047.

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The aim of this study is to establish an ovarian stress model, and to investigate the effects of stress on follicular development. Our data showed that continuous intraperitoneal injection of CORT successfully created a stressful environment in the ovary. To assess the effects of CORT on ovarian functions, 80 three-week-old ICR (Institute of Cancer Research) female mice were randomly divided into control group and treatment group. All mice were injected intraperitoneally with pregnant horse serum gonadotropin (PMSG). At the same time, the treatment group were injected with CORT (1 mg/mouse) at intervals of 8 h; while the control group was injected with same volume of methyl sulfoxide (DMSO). Blood, ovaries, or ovarian granulosa cell samples were collected at 24 h, 48 h, and 55 h after PMSG injection. The results showed that, compared with the control group, CORT-injected mice revealed a significant decrease in ovulation rates, ovarian weight, ovarian index, the number of secondary follicles and mature follicles, levels of estrogen and progesterone, and mRNA expression of steroid synthase-related genes. Collectively, our findings clearly demonstrated that CORT injection could represent an effective practice to simulate stresses that inhibit ovarian functions by reducing follicular development and ovulation.
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26

Branco, Ilka S. L., Danielle L. Viana, Renata T. S. Félix, Dráusio P. Véras, and Fábio H. V. Hazin. "Oocyte development and ovarian maturation of the black triggerfish, Melichthys niger(Actinopterygii: Balistidae) in São Pedro e São Paulo Archipelago, Brazil." Neotropical Ichthyology 11, no. 3 (September 2013): 597–606. http://dx.doi.org/10.1590/s1679-62252013000300013.

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The oogenesis is a key stage in the reproductive development of an organism, which can be best understood from histological analysis of ovaries in different maturity stages. In order to provide information on the reproductive biology of the black triggerfish, M. niger, in particular on its oogenesis process, this study aimed at identifying and characterizing the oocyte development stages and its organization within the different stages of ovarian maturation based on specimens from São Pedro e São Paulo Archipelago. In this present report, a number of 294 ovaries were histologically analyzed. It was verified that they are composed of ovigerous lamellae containing oocytes at different development stages. Five different stages of oogenesis were identified: young cells, with an average size of 12.9 ìm; previtellogenic oocytes (perinucleolar), with an average size of 53.5 ìm; cortical-alveoli oocytes with an average size of 83.1 ìm; vitellogenic oocytes, with an average size of 160.4 ìm and mature oocytes, with an average size of 289.8 ìm. In addition to the germ cells, some somatic structures were also identified, such as: ovarian wall, follicular cells and blood vessels. Based on the type and number of oocytes observed, four stages of ovarian maturation were identified: early maturation, represented by only 2.2% of the sample; middle maturation, represented by 9.9%; mature, represented by 44.2% and resting, represented by 43.9%. The identification of five oocyte development stages in the ovarians from M. niger, suggested that the specie follows a pattern similar to that described for other marine fish.
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27

Brown, H. M., R. L. Robker, and D. L. Russell. "256. Ovarian lymphatic vascular development is hormonally regulated and Adamts1-dependent." Reproduction, Fertility and Development 20, no. 9 (2008): 56. http://dx.doi.org/10.1071/srb08abs256.

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The lymphatic system is important for return of extra-vascular fluid to the blood circulation, conductance of hormones and immune cell trafficking. Delicate hormonal control of fluid conductance during reproductive cycles is exemplified by the ovarian hyperstimulation syndrome, a dangerous condition of hypovolemia caused by fluid accumulation in the abdomen and reproductive tissues, in response to hormonal hyperstimulation. This study is the first to investigate the relationship between ovarian lymphatic development and follicle growth. Quantitative morphometric analysis of vessel size and number in mouse ovary revealed, for the first time, that the ovarian lymphatic vasculature develops postnatally and in synchrony with the induction of ovarian CYP19a1 (Aromatase); the time when secondary follicles become FSH-responsive and estrogenic. Mechanistically, we found that the FSH-analogue eCG mediates induction of lymphatic vascular endothelial growth factor Vegfd and the receptor Vegfr3 (Flt4) in granulosa cells. Importantly, stimulation with eCG also enhanced ovarian lymphatic vessel number and size. However, formation of ovarian lymphatics also required the matrix-remodelling protease Adamts1, since ovaries from Adamts1−/− mice failed to undergo normal lymphatic vascular development. Treatment of Adamts1 null mice with eCG significantly increased the number and size of ovarian lymphatic vessels, however, the vessels were still smaller and fewer in number than wildtypes. These combined results indicate that the ovarian lymphatic system develops in response to hormonal signals, which promote folliculogenesis, through induction of lymphangiogenic factors in granulosa cells; as well as involving Adamts1-dependent mechanisms. This study is the first demonstration of the novel principle of hormonal regulation of lymphangiogenesis in any tissue and suggests a requirement for functional lymphatics during normal folliculogenesis. In addition our results inform the elucidation of the tightly regulated processes that control fluid dynamics and immune cell surveillance within reproductive tissues.
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28

Meng, Li, Verena Coleman, Yu Zhao, Mario Ost, Anja Voigt, Annelies Bunschoten, Jaap Keijer, Katja Teerds, and Susanne Klaus. "Pseudo-Starvation Driven Energy Expenditure Negatively Affects Ovarian Follicle Development." International Journal of Molecular Sciences 22, no. 7 (March 30, 2021): 3557. http://dx.doi.org/10.3390/ijms22073557.

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In the present investigation, we examined whether a change in whole body energy fluxes could affect ovarian follicular development, employing mice ectopically expressing uncoupling protein 1 in skeletal muscle (UCP1-TG). Female UCP1-TG and wild-type (WT) mice were dissected at the age of 12 weeks. Energy intake and expenditure, activity, body weight and length, and body composition were measured. Plasma insulin, glucose, leptin, plasma fibroblast growth factor 21 (FGF21) and plasma insulin-like growth factor 1 (IGF1) levels were analyzed and ovarian follicle and corpus luteum numbers were counted. IGF1 signaling was analyzed by immunohistochemical staining for the activation of insulin receptor substrate 1/2 (IRS1/2) and AKT. UCP1-TG female mice had increased energy expenditure, reduced body size, maintained adiposity, and decreased IGF1 concentrations compared to their WT littermates, while preantral and antral follicle numbers were reduced by 40% and 60%, respectively. Corpora lutea were absent in 40% of the ovaries of UCP1-TG mice. Phospho-IRS1, phospho-AKT -Ser473 and -Thr308 immunostaining was present in the granulosa cells of antral follicles in WT ovaries, but faint to absent in the antral follicles of UCP1-TG mice. In conclusion, the reduction in circulating IGF1 levels due to the ectopic expression of UCP1 is associated with reduced immunostaining of the IRS1-PI3/AKT pathway, which may negatively affect ovarian follicle development and ovulation.
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29

Ryazantseva, Ekaterina M., Elena V. Misharina, Vladimir V. Potin, and Marina A. Tarasova. "Role hyperleptinemia, insulin resistance and hyperestrogenemia in the development of ovarian failure in women with obesity." Journal of obstetrics and women's diseases 65, no. 5 (September 15, 2016): 56–63. http://dx.doi.org/10.17816/jowd65556-63.

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Actuality of the study. Ovarian insufficiency is present in more that 30% of reproductive age women. The role of leptine and insuin resistance in the pathogenesis of ovarian insufficiency is not yet established and has to be clarified. The aim of the study to investigate the role of hyperleptinemia, insulin resistance and hyperestrogenemia in the pathogenesis of ovarian insufficiency in obesity.Materials and methods. Fifty reproductive age women with BMI > 25,6 kg/m2 were studied. Ten healthy reproductive age women were included as controls. The plasma level of leprin, honadotropins, prolactin, insulin and sex steroid hormones assayed by immunoenzyme analysis, morning fasting blood glucose and the glucose level after glucose tolerance test, pelvic echography, “whole body” program of dual x-ray absorptiometry were studied in both patients and controls.Results. Thirty-six out of 50 women had signs of ovarian insufficiency. The presence and severity of ovarian insufficiency did not correlate with the level of leptin in blood or with insulin resistance. The positive correlation between oestradiol level and both presence and severity of ovarian insufficiency could be demonstrated.Conclusion. The results of our study do not support the hyperleptinemia and insulin resistance as the main cause of ovarian insufficiency in alimentary obesity. The most potential reason of anovulation in these women could be hyperoestrogenia due to increased conversion of androgens into oestrogenes in fat tissues and ovaria.
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30

Dissen, Gregory A., Cecilia Garcia-Rudaz, Alfonso Paredes, Christine Mayer, Artur Mayerhofer, and Sergio R. Ojeda. "Excessive Ovarian Production of Nerve Growth Factor Facilitates Development of Cystic Ovarian Morphology in Mice and Is a Feature of Polycystic Ovarian Syndrome in Humans." Endocrinology 150, no. 6 (March 5, 2009): 2906–14. http://dx.doi.org/10.1210/en.2008-1575.

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Although ovarian nerve growth factor (NGF) facilitates follicular development and ovulation, an excess of the neurotrophin in the rodent ovary reduces ovulatory capacity and causes development of precystic follicles. Here we show that ovarian NGF production is enhanced in patients with polycystic ovarian syndrome (PCOS) and that transgenically driven overproduction of NGF targeted to the ovary results in cystic morphology, when accompanied by elevated LH levels. NGF levels are increased in the follicular fluid from PCOS ovaries and in the culture medium of granulosa cells from PCOS patients, as compared with non-PCOS patients. Ovaries from transgenic mice carrying the NGF gene targeted to thecal-interstitial cells by the 17α-hydroxylase gene promoter produce more NGF than wild-type (WT) ovaries and are hyperinnervated by sympathetic nerves. Antral follicle growth is arrested resulting in accumulation of intermediate size follicles, many of which are apoptotic. Peripubertal transgenic mice respond to a gonadotropin challenge with a greater increase in plasma 17-hydroxyprogesterone, estradiol, and testosterone levels than WT controls. Transgenic mice also exhibit a reduced ovulatory response, delayed puberty, and reduced fertility, as assessed by a prolonged interval between litters, and a reduced number of pups per litter. Sustained, but mild, elevation of plasma LH levels results in a heightened incidence of ovarian follicular cysts in transgenic mice as compared with WT controls. These results suggest that overproduction of ovarian NGF is a component of polycystic ovarian morphology in both humans and rodents and that a persistent elevation in plasma LH levels is required for the morphological abnormalities to appear.
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31

Nicol, Barbara, Karina Rodriguez, and Humphrey H.-C. Yao. "Aberrant and constitutive expression of FOXL2 impairs ovarian development and functions in mice." Biology of Reproduction 103, no. 5 (August 25, 2020): 966–77. http://dx.doi.org/10.1093/biolre/ioaa146.

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Abstract Development and functions of the ovary rely on appropriate signaling and communication between various ovarian cell types. FOXL2, a transcription factor that plays a key role at different stages of ovarian development, is associated with primary ovarian insufficiency and ovarian cancer as a result of its loss-of-function or mutations. In this study, we investigated the impact of aberrant, constitutive expression of FOXL2 in somatic cells of the ovary. Overexpression of FOXL2 that started during fetal life resulted in defects in nest breakdown and consequent formation of polyovular follicles. Granulosa cell differentiation was impaired and recruitment and differentiation of steroidogenic theca cells was compromised. As a consequence, adult ovaries overexpressing FOXL2 exhibited defects in compartmentalization of granulosa and theca cells, significant decreased steroidogenesis and lack of ovulation. These findings demonstrate that fine-tuned expression of FOXL2 is required for proper folliculogenesis and fertility.
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32

Leung, Peter C. K. "Ovarian follicular development and regression." Canadian Journal of Physiology and Pharmacology 67, no. 8 (August 1, 1989): 953. http://dx.doi.org/10.1139/y89-149.

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Many exciting developments in mammalian reproductive research with far-reaching consequences have occurred in recent years. To highlight the significance of some of these developments, a symposium on the theme of ovarian follicular development and regression was organized, and held at the joint meeting of the American Physiological Society and the Canadian Physiological Society, in Montréal in October 1988. Several leading researchers, from both Canada and the U.S.A., in various aspects of ovarian research, participated in the symposium. The topics of discussion ranged from the role of growth factors and novel intraovarian regulators during follicular development, to molecular aspects of ovarian hormone production, to the functional regression of the corpus luteum. It is expected that the following proceedings will serve as a reference for researchers concerned with reproductive endocrinology as well as providing a foundation for future collaborative study.
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33

Parra, Claudio, Jenny L. Fiedler, S. Leticia Luna, Monika Greiner, Vasantha Padmanabhan, and Hernán E. Lara. "Participation of vasoactive intestinal polypeptide in ovarian steroids production during the rat estrous cycle and in the development of estradiol valerate-induced polycystic ovary." Reproduction 133, no. 1 (January 2007): 147–54. http://dx.doi.org/10.1530/rep.1.01214.

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Vasoactive intestinal polypeptide (VIP) stimulates estradiol and progesterone release from ovarian granulosa cells in vitro. Very little information is available as to the role VIP plays in the control of steroid secretion during reproductive cyclicity and in ovarian pathologies involving altered steroid secretion. In this study, we determined the involvement of VIP in regulating ovarian androgen and estradiol release during estrous cyclicity and estradiol valerate (EV)-induced polycystic ovarian development in rats. Our findings show that androgen and estradiol release from ovaries obtained during different stages of rat estrous cycle mimic cyclic changes in steroid release observed in vivo with maximal release occurring during late proestrus. VIP increased androgen release from ovaries of all cycle stages except late proestrus and estradiol release from all cycle stages. Increases in VIP-induced androgen and estradiol release were maximal at early proestrus. Inclusion of saturating concentrations of androstenedione increased magnitude of VIP-induced estradiol release at diestrus and estrus but not proestrus. Magnitude of VIP-induced androgen and estradiol release tended to be greater in the ovaries from EV-treated rats with polycystic ovary compared with estrous controls. At the tissue level, ovarian VIP concentration was cycle stage dependent with highest level seen in diestrus. Maximum concentration of VIP was found in EV-treated rats. Changes in VIP were inversely related to changes in ovarian nerve growth factor, a neuropeptide involved in ovarian androgen secretion. These results strongly suggest that intraovarian VIP participates in the control of estradiol secretion during the rat estrous cycle and possibly in the maintenance of increased ovarian estradiol secretory activity of EV-treated rats.
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34

Park, Min Jung, Jun-Woo Ahn, Ki Hyung Kim, Junghee Bang, Seung Chul Kim, Jae Yi Jeong, Ye Eun Choi, Chang-Woon Kim, and Bo Sun Joo. "Prediction of ovarian aging using ovarian expression of BMP15, GDF9, and C-KIT." Experimental Biology and Medicine 245, no. 8 (March 29, 2020): 711–19. http://dx.doi.org/10.1177/1535370220915826.

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This study investigated ovarian expressions of bone morphogenetic protein 15 (BMP15), growth differentiation factor 9 (GDF9), and C-KIT according to age in female mice to determine whether these factors can be served as new potential biomarkers of ovarian aging. Ovaries were collected from mice aged 10, 20, 30, and 40 weeks, and ovarian expressions of BMP15, GDF9, and C-KIT were examined by real-time PCR, Western blot, and immunohistochemistry. Follicle counts were measured on histological hematoxylin and eosin staining. In the second experiment to evaluate ovarian function, after superovulation with PMSG and hCG, the numbers of zygotes retrieved and embryo development rate were examined. Ovarian expressions of BMP15, GDF9, and C-KIT decreased with age. Follicle counts, numbers of retrieved zygotes, and embryo development rate were also significantly reduced in old mice over 30 weeks compared with young mice. These results indicate that these factors could be served as new potential biomarkers of ovarian aging. Impact statement Ovarian aging is becoming a more important issue in terms of fertility preservation and infertility treatment. Serum anti-Mullerian hormone (AMH) level and antral follicle count (AFC) are being practically used as markers of ovarian aging as well as ovarian reserve in human. However, these factors have some drawbacks in assessing ovarian aging and reserve. Therefore, the identification of ovarian expressions of BMP15, GDF9, and C-KIT according to female could be applied as a potent predictor of ovarian aging. This work provides new information on the development of diagnosis and treatment strategy of age-related fertility decline and premature ovarian insufficiency.
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35

Praxedes, Érica C. G., Gabriela L. Lima, Luana G. P. Bezerra, Fernanda A. Santos, Marcelo B. Bezerra, Denise D. Guerreiro, Ana P. R. Rodrigues, Sheyla F. S. Domingues, and Alexandre R. Silva. "Development of fresh and vitrified agouti ovarian tissue after xenografting to ovariectomised severe combined immunodeficiency (SCID) mice." Reproduction, Fertility and Development 30, no. 3 (2018): 459. http://dx.doi.org/10.1071/rd17051.

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The aim of the present study was to evaluate the development of fresh and vitrified agouti ovarian tissue after xenografting to C57Bl/6 severe combined immunodeficiency (SCID) female mice. Ovaries were obtained from five female agoutis and divided into 16 fragments. Five fragments were transplanted immediately to ovariectomised SCID mice and the others were vitrified, stored for 2 weeks and transplanted only after rewarming. Tissue fragments were transplanted under the kidney capsule in recipients. The return of ovarian activity in recipients was monitored by the observation of external signs of oestrus and vaginal cytology over a period of 40 days after transplantation, after which the grafts were removed and evaluated for morphology, cell proliferation and the occurrence of DNA fragmentation. Ovarian activity returned in four of five mice that received fresh ovarian tissue from agoutis and in one of six mice that had received vitrified tissue a mean (± s.e.m.) 20.6 ± 8.6 days after xenotransplantation. After graft removal, a predominance of primordial and primary follicles was observed in all grafts. Vitrification reduced cell proliferation and increased the occurrence of DNA fragmentation in grafted agouti ovarian tissue. In conclusion, the present study demonstrates that xenografted agouti ovarian tissue, fresh or vitrified, is able to promote the return of ovarian activity in ovariectomised SCID C57B1/6 mice. However, improvements to vitrification protocols for agouti ovarian tissue are necessary.
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36

van der Schoot, P., and W. J. de Greef. "Development of ovarian follicles during lactation in rats." Acta Endocrinologica 112, no. 2 (June 1986): 247–52. http://dx.doi.org/10.1530/acta.0.1120247.

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Abstract. Ovarian follicular development was studied during lactation in rats. At an early stage of lactation (day 7) the ovaries showed only small follicles in agreement with the expected 'follicular quiescence' during lactation. However, at a more advanced stage of lactation (day 14), there were large follicles which were capable of ovulation in response to exogenous gonadotropins. Unilateral ovariectomy early during lactation (day 2) resulted in compensatory follicular development in the remaining ovary. However, doubling of the number of large follicles per ovary had not yet occurred by day 13. Unilateral ovariectomy caused a significant prolongation of the delay of embryonic implantation in pregnant lactating rats: this probably reflected delay of the development of sufficiently large numbers of oestrogen-producing follicles for this process. Unilateral ovariectomy did not affect the length of lactational pseudopregnancy. The findings indicate that 'follicular quiescence' during lactation in rats is limited to the very first period after parturition. This limitation may result from the relative ineffectiveness of suckling to suppress the secretion of FSH. In this respect, ovarian follicular development in rats differs from that in many other species, including primates and man.
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37

Maretta, M., and E. Marettová. "Toxic Effects of Cadmium on the Female Reproductive Organs a Review." Folia Veterinaria 66, no. 4 (December 1, 2022): 56–66. http://dx.doi.org/10.2478/fv-2022-0038.

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Abstract Cadmium (Cd) is a common environmental pollutant present in soil and associated with many modern industrial processes. Cadmium may adversely influence the health of experimental animals and humans and exert significant effects on the reproductive tract morphology and physiology. During embryonic development, cadmium suppresses the normal growth and development of the ovaries, and in adults it disrupts the morphology and function of the ovaries and uterus. The exposure to cadmium has adverse effects on the oocyte meiotic maturation affecting the structure of ovarian tissue. The distribution of follicles and corpus luteum in the ovarian tissues has been shown to be disrupted, affecting the normal growth and development of the follicles. In the ovarian cortex, the number of follicles at different stages of maturation decreased, and the number of atretic follicles increased. In the medulla, oedema and ovarian haemorrhage and necrosis appears at higher doses. Granulosa cells exposed to cadmium exhibited morphological alterations. Oocyte development was inhibited and the amount of oocyte apoptosis was higher. Cadmium exposure also caused changes in the structure of the ovarian blood vessels with reduction in the vascular area. Cadmium effects included increased uterine weight, hyperplasia and hypertrophy of the endometrial lining. Exposure to cadmium had specific effects on gonadal steroidogenesis by suppressing steroid biosynthesis of the ovarian granulosa cells and luteal cells. Progesterone, follicle stimulating hormone, and luteinizing hormone decreased significantly after CdCl2 administration. Cadmium can suppress the female’s ovulation process and cause temporary infertility.
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38

Forsdike, Rachel A., Kate Hardy, Lauren Bull, Jaroslav Stark, Lisa J. Webber, Sharron Stubbs, Jane E. Robinson, and Stephen Franks. "Disordered follicle development in ovaries of prenatally androgenized ewes." Journal of Endocrinology 192, no. 2 (February 2007): 421–28. http://dx.doi.org/10.1677/joe.1.07097.

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Exposure to excess androgens in utero induces irreversible changes in gonadotrophin secretion and results in disrupted reproductive endocrine and ovarian function in adulthood, in a manner reminiscent of the common clinical endocrinopathy of polycystic ovary syndrome (PCOS). We have recently identified an abnormality in early follicle development in PCOS which we suggested might be an androgenic effect. We propose that altered ovarian function in androgenized ewes is due to prenatal androgens not only causing an abnormality of gonadotrophin secretion, but also exerting a direct effect on the early stages of folliculogenesis. Therefore, in this study, we explored the possible differences between small preantral follicles in the ovarian cortex of androgenized female lambs with those of normal lambs. At 8 months of age, small ovarian cortical biopsies (approximately 5 mm3) were obtained at laparotomy from nine female lambs that had been exposed to androgens in utero from embryonic days 30 to 90 of a 147-day pregnancy, and 11 control female lambs. Further, ovarian tissue was obtained at 20 months of age from ten androgenized and nine control animals. Tissue was either fixed immediately for histology or cultured for up to 15 days prior to fixing. The number of follicles in haematoxylin and eosin-stained sections was counted and recorded along with the stage of development. Before culture, the total follicle density (follicles/mm3 tissue) was not statistically significantly different between the two types of ovary at either 8 or 20 months of age. Furthermore, there were no statistically significant differences in the density of follicles at each stage of development. However, there was a lower percentage of primordial follicles, but a higher percentage of primary follicles, in biopsies taken at 8 months from androgenized lambs when compared with controls. At 20 months, the proportions of follicles at the primordial and primary stages were not significantly different between the two groups, but this was mainly attributable to an increase in the proportion of growing follicles in biopsies from control animals. Culture of ovarian cortex from 8-month-old lambs resulted in a progressive increase in the proportion of growing follicles when compared with tissue fixed on the day of surgery. However, there was no difference between androgenized and control tissue in the percentage of growing follicles. The increase in the proportion of growing follicles in the cortex of androgenized animals is reminiscent of similar observations in human polycystic ovaries and suggests that excess exposure to androgen in early life plays a part in the accelerated progression of follicle development from the primordial to the primary stage in polycystic ovaries.
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39

Lengyel, Ernst. "Ovarian Cancer Development and Metastasis." American Journal of Pathology 177, no. 3 (September 2010): 1053–64. http://dx.doi.org/10.2353/ajpath.2010.100105.

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40

Zhao, Han, and Aleksandar Rajkovic. "MicroRNAs and Mammalian Ovarian Development." Seminars in Reproductive Medicine 26, no. 06 (October 24, 2008): 461–68. http://dx.doi.org/10.1055/s-0028-1096126.

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41

Tevosian, S. G. "Genetic Control of Ovarian Development." Sexual Development 7, no. 1-3 (2013): 33–45. http://dx.doi.org/10.1159/000339511.

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42

Pangas, Stephanie. "Growth Factors in Ovarian Development." Seminars in Reproductive Medicine 25, no. 4 (July 2007): 225–34. http://dx.doi.org/10.1055/s-2007-980216.

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43

Uhlenhaut, Nina Henriette, and Mathias Treier. "Foxl2 function in ovarian development." Molecular Genetics and Metabolism 88, no. 3 (July 2006): 225–34. http://dx.doi.org/10.1016/j.ymgme.2006.03.005.

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44

Erickson, Gregory F., and Douglas R. Danforth. "Ovarian control of follicle development." American Journal of Obstetrics and Gynecology 172, no. 2 (February 1995): 736–47. http://dx.doi.org/10.1016/0002-9378(95)90147-7.

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45

Tomic, Dragana, Kimberly P. Miller, Hilary A. Kenny, Teresa K. Woodruff, Patricia Hoyer, and Jodi A. Flaws. "Ovarian Follicle Development Requires Smad3." Molecular Endocrinology 18, no. 9 (September 1, 2004): 2224–40. http://dx.doi.org/10.1210/me.2003-0414.

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Abstract Smad3 is an important mediator of the TGFβ signaling pathway. Interestingly, Smad3-deficient (Smad3−/−) mice have reduced fertility compared with wild-type (WT) mice. To better understand the molecular mechanisms underlying the reduced fertility in Smad3−/− animals, this work tested the hypothesis that Smad3 deficiency interferes with three critical aspects of folliculogenesis: growth, atresia, and differentiation. Growth was assessed by comparing the size of follicles, expression of proliferating cell nuclear antigen, and expression of cell cycle genes in Smad3−/− and WT mice. Atresia was assessed by comparing the incidence of atresia and expression of bcl-2 genes involved in cell death and cell survival in Smad3−/− and WT mice. Differentiation was assessed by comparing the expression of FSH receptor (FSHR), estrogen receptor (ER) α, ERβ, and inhibin α-, βA-, and βB-subunits in Smad3−/− and WT mice. Because growth, atresia, and differentiation are regulated by hormones, estradiol, FSH, and LH levels were compared in Smad3−/− and WT mice. Moreover, because alterations in folliculogenesis can affect the ability of mice to ovulate, the number of corpora lutea and ovulated eggs in response to gonadotropin treatments were compared in Smad3−/− and WT animals. The results indicate that Smad3 deficiency slows follicle growth, which is characterized by small follicle diameters, low levels of proliferating cell nuclear antigen, and low expression of cell cycle genes (cyclin-dependent kinase 4 and cyclin D2). Smad3 deficiency also causes atretic follicles, degenerated oocytes, and low expression of bcl-2. Furthermore, Smad3 deficiency affects follicular differentiation as evidenced by decreased expression of ERβ, increased expression of ERα, and decreased expression of inhibin α-subunits. Smad3 deficiency causes low estradiol and high FSH levels. Finally, Smad3−/− ovaries have no corpora lutea, and they do not ovulate after ovulatory induction with exogenous gonadotropins. Collectively, these data provide the first evidence that reduced fertility in Smad3−/− mice is due to impaired folliculogenesis, associated with altered expression of genes that control cell cycle progression, cell survival, and cell differentiation. The findings that Smad3−/− follicles have impaired growth, increased atresia, and altered differentiation in the presence of high FSH levels, normal expression of FSHR, and lower expression of cyclin D2, suggest a possible interaction between Smad3 and FSH signaling downstream of FSHR in the mouse ovary.
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46

Miyano, T., J. Akamatsu, S. Kato, I. Nanjo, and S. Kanda. "Ovarian development in Meishan pigs." Theriogenology 33, no. 4 (April 1990): 769–75. http://dx.doi.org/10.1016/0093-691x(90)90812-8.

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47

Dissen, Gregory A., Carmen Romero, Alfonso Paredes, and Sergio R. Ojeda. "Neurotrophic control of ovarian development." Microscopy Research and Technique 59, no. 6 (December 4, 2002): 509–15. http://dx.doi.org/10.1002/jemt.10227.

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48

Barua, Animesh, Aparna Yellapa, Salvatore A. Grasso, Jacques S. Abramowicz, Sameer Sharma, Alfred S. Guirguis, Sanjib Basu, and Pincas Bitterman. "Expression of glucose-regulated protein 78 (GRP78) and its regulator microrna-181 during the development and progression of ovarian cancer." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): 5579. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.5579.

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5579 Background: Ovarian cancer (OVCA) is a lethal malignancy of women with a distinct pattern of metastasis through peritoneal dissemination. Sustained exposure of the ovaries to oxidative stress due to inflammatory processes including ovulatory genotoxicity, makes the ovarian microenvironment conducive to malignant cell proliferation. GRP78 is a stress-inducible protein which resides in the endoplasmic reticulum of the cell. Thus GRP78 may be a marker of ovarian tumor associated stress and could represent a therapeutic target for OVCA. The goal of this study was to examine if GRP78 expression increases in association with OVCA development and determine the molecular mechanism of its increase in ovarian tumors. Methods: All tissues were collected from patients who underwent surgery and processed for immunohistochemistry (IHC), proteomic study (2D-WB) and miRNA expression. Expression of GRP78 was examined in paraffin sections of normal ovaries (n = 20), benign (serous cystadenoma, n = 15 and cystadenofibroma, n = 5) and ovaries with papillary serous carcinoma at early stage (n= 20 at stages I and II) and late stage (n = 20, stages III and IV) by IHC and confirmed by 2D-WB (representative samples). Changes in miRNA-181 (post-translation regulator of GRP78) expression were examined by qRT-PCR. Results: GRP78 expression by normal ovarian surface epithelium and epithelium of benign tumors was very weak. In contrast, the intensity of GRP78 expression was significantly (p<0.05) high in early stage OVCA and increased further in late stage OVCA. An immunoreactive band of 78kDa detected by 2D-WB confirmed IHC observations. In contrast, expression of miRNA-181 by malignant tumors significantly (p<0.05) decreased as the tumor progressed to late stages. Conclusions: The results of the present study suggest that GRP78 expression is associated with the development and progression of malignant ovarian tumors. Increase in GRP78 expression was associated with the down-regulation of miRNA-181. Expression of GRP78 by malignant ovarian epithelium represents a potential marker with usefulness for targeted drug delivery. Support: Elmer and Sylvia Sramek Foundation.
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49

Chow, Stephanie, Jonathan S. Berek, and Oliver Dorigo. "Development of Therapeutic Vaccines for Ovarian Cancer." Vaccines 8, no. 4 (November 5, 2020): 657. http://dx.doi.org/10.3390/vaccines8040657.

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Ovarian cancer remains the deadliest of all gynecologic malignancies. Our expanding knowledge of ovarian cancer immunology has allowed the development of therapies that generate systemic anti-tumor immune responses. Current immunotherapeutic strategies include immune checkpoint blockade, cellular therapies, and cancer vaccines. Vaccine-based therapies are designed to induce both adaptive and innate immune responses directed against ovarian cancer associated antigens. Tumor-specific effector cells, in particular cytotoxic T cells, are activated to recognize and eliminate ovarian cancer cells. Vaccines for ovarian cancer have been studied in various clinical trials over the last three decades. Despite evidence of vaccine-induced humoral and cellular immune responses, the majority of vaccines have not shown significant anti-tumor efficacy. Recently, improved vaccine development using dendritic cells or synthetic platforms for antigen presentation have shown promising clinical benefits in patients with ovarian cancer. In this review, we provide an overview of therapeutic vaccine development in ovarian cancer, discuss proposed mechanisms of action, and summarize the current clinical experience.
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50

Vaskivuo, Tommi E., Minna Mäentausta, Svea Törn, Olayiwola Oduwole, Annika Lönnberg, Riitta Herva, Veli Isomaa, and Juha S. Tapanainen. "Estrogen Receptors and Estrogen-Metabolizing Enzymes in Human Ovaries during Fetal Development." Journal of Clinical Endocrinology & Metabolism 90, no. 6 (June 1, 2005): 3752–56. http://dx.doi.org/10.1210/jc.2004-1818.

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Estrogen action plays a crucial role in many processes throughout the human life span, including development. Estrogens are pivotal in the regulation of female reproduction, but little is known about their role during ovarian development. To better understand estrogen action during ovarian development, the expression of estrogen receptors (ERs)-α and -β and key enzymes regulating estradiol production, 17β-hydroxysteroid dehydrogenases (17HSDs) types 1, 2, and 7, were analyzed in human fetal ovaries. The expression of ERs was related to the development of ovarian follicles. Before the 26th week of fetal life ERα was only occasionally detected, but from then onward, its expression was detected in ovarian follicles. Consistent expression of ERβ was seen from the 20th week until term. Both ERα and ERβ were localized to the granulosa cells and oocytes. Expression of 17HSD1 and 17HSD7 enzymes, catalyzing the conversion of estrone to more active estradiol, was detected as early as at the 17th week of fetal life. The expression of 17HSD1 displayed a pattern similar to that of ERs and increased toward term, whereas that of 17HSD7 decreased and was negative by the 36th week. 17HSD1 was localized to the granulosa cells, whereas 17HSD7 expression was more diffuse and was found in both granulosa and stromal cells. 17HSD2, converting estradiol to less potent estrone, was negative in all samples studied. The simultaneous appearance of estrogen-converting enzymes and ERs at the time of follicle formation indicates that the machinery for estrogen action exists in fetal ovaries and suggests a possible role for estrogens in the developing ovary.
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