Auswahl der wissenschaftlichen Literatur zum Thema „Physiologie placentaire“

Placental efflux transporters such as P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) protect the developing fetus from exposure to potentially toxic xenobiotics. However, little is known about the expression of these transporters in human placentae of different gestational ages. Therefore, we quantified the expression of P-gp and BCRP in human placentae of different gestational ages. We also measured the expression of various nuclear regulatory factors such as the pregnane xenobiotic factor to determine whether their expression also changes with gestational age. Syncitial microvillous plasma membranes were isolated from human placentae of various gestational ages (60–90 days, 90–120 days, and full-term C-section placentae). P-gp and BCRP expression (protein) in these preparations were measured by Western blot analysis followed by an ELISA. Expression (mRNA) of P-gp, BCRP, and nuclear regulatory factors in the placentae were quantified by quantitative real-time PCR. P-gp expression (relative to that of alkaline phosphatase) was significantly ( P < 0.05) higher (44.8-fold as protein; 6.5-fold as mRNA) in early gestational age human placentae (60–90 days) vs. term placentae. In contrast, BCRP (protein and mRNA) and nuclear regulatory factors (mRNA) expression in placental tissue did not change significantly with gestational age. However, placental expression of P-gp and human chorionic gonadotropin-β (hCG-β) transcripts was highly correlated ( r = 0.73; P < 0.0001; Spearman rank correlation). Expression of P-gp, but not BCRP, decreases dramatically with gestational age in human placentae. This decrease in P-gp expression is not caused by a change in expression of nuclear receptor transcripts but appears to be related to hCG-β expression. The placental P-gp expression appears to be upregulated in early pregnancy to protect the fetus from xenobiotic toxicity at a time when it is most vulnerable to such toxicity.

One of the major targets of antiphospholipid antibodies (aPL) is the placenta, the evolution of which during pregnancy has been well documented. Histopathological findings are related to gestational age, and several physiologic and pathologic alterations that occur during its development. The major findings in placentae from aPL positive patients are thrombosis, acute atherosis, a decreased number of syncytio-vascular membranes, increased number of syncytial knots and obliterative arteriopathy. These findings are not specific to the antiphospholipid syndrome (APS) and sometimes do not correlate with the fetal outcome. Histopathological study of placentae may elucidate mechanisms of action of aPL in fetal loss and other obstetric complications. In addition, it may assist in the investigation of the differential diagnosis between APS and pregnancy-induced hypertension. Immunohistochemical studies of local placental proteins contribute to this differential diagnosis.

Introduction: Several cases of chorioangiomas have been described, however, there is little or no bibliography about the neonatal management of children born to mothers with this condition. Therefore, it is of utmost importance to have an approach to this type of pathology in order to venture a little more in the possible optimal management of these patients. Clinical case: Two patients with high cardiac output, who were given a high cardiovascular risk profile, however, extreme measures were taken at birth, especially physiological clamping of the umbilical cord, which improved cardiac output according to the decrease in vascular resistance at birth, improving the outcome of the patients, with minimal requirements for ventilatory support and short in-hospital stays. Conclusions: Physiologic clamping is a practice that should be made routine in patients with this prenatal history, who show combined cardiac output and elevated cardiovascular risk.

Neonatal mortality and morbidity are substantial issues affecting the maternal healthcare sector. Extremely premature infants, notably those born before the 28-week mark, experience significant morbidity and mortality rates during neonatal care. This is a result of developmental immaturity and iatrogenic injury. Several attempts have been made to develop a womb-like environment to mimic uteroplacental physiology, but limited success has been noted over the last decade. This review aims to summarize the current literature on improved techniques implemented in creating an artificial placenta, the principles of these procedures, and their limitations. Our findings indicate that implementing techniques that closely mimic uteroplacental pathophysiology is crucial in decreasing the excessive neonatal mortality and morbidity rates seen in extremely premature infants.

Abstract Trophoblast-enriched cell suspensions prepared by collagenase digestion from midterm murine placentae were found resistant to CTL-mediated lysis. Treatment of such cells by trypsin or neuraminidase rendered these cells susceptible to such lytic effectors. Collagenase-prepared cell suspensions could impair CTL action, whereas neuraminidase- or trypsin-treated cells did not retain this property. This effect was also observed with extracts. These results indicate that soluble factors (which we will characterize in another paper) released by trophoblast cells (in fact, spongiotrophoblast) can interfere in a dose-dependent fashion with the action of lytic effectors. We suggest that such active mechanisms are physiologic components of the placental barrier and might be defective in some cases of immunologic abortions.

Early miscarriage (EMC) is a devastating obstetrical complication. ATP-binding cassette (ABC) transporters mediate cholesterol transfer across the placenta and enhance cell survival by effluxing substrates from target cells in the presence of stressors. Recent evidence reports an intricate interplay between autophagy and ABC transporters. We hypothesized that dysregulated autophagy and oxidative stress (OS) in the placenta leads to abnormal expression of membrane transporters contributing to poor pregnancy survival in EMC. We determined mRNA and protein expression of autophagy genes (Beclin-1/Bcl-2/LC3I/LC3II/p62) and ABC transporters (ABCA1/ABCG1/ABCG2) in placentae from EMC patients (n = 20), term controls (n = 19), first trimester (n = 6), and term controls (n = 5) controls. Oxidative/antioxidant status and biomarkers of oxidative damage were evaluated in maternal serum and placentae from EMC and healthy controls. In EMC, placental expression of LC3II/LC3I as well as of the key autophagy regulatory proteins Beclin-1 and Bcl-2 were reduced, whereas p62 was increased. Both in the serum and placentae of EMC patients, total OS was elevated reflected by increased oxidative damage markers (8-OHdG/malondialdehyde/carbonyl formation) accompanied by diminished levels of total antioxidant status, catalase, and total glutathione. Furthermore, we found reduced ABCG1 and increased ABCG2 expression. These findings suggest that a decreased autophagy status triggers Bcl-2-dependent OS leading to macromolecule damage in EMC placentae. The decreased expression of ABCG1 contributes to reduced cholesterol export to the growing fetus. Increasing ABCG2 expression could represent a protective feedback mechanism under inhibited autophagy conditions. In conclusion, dysregulated autophagy combined with increased oxidative toxicity and aberrant expression of placental ABC transporters affects materno-fetal health in EMC.

L’estradiol (E2) accélère la maturation pulmonaire et la 17β-hydroxystéroïde déshydrogénase de type 2 (17ßHSD2) inactive les estrogènes et les androgènes. L’expression de la 17ßHSD2 fluctue et culmine dans le poumon foetal murin au jour gestationnel 17,5. Les fluctuations de la 17ßHSD2 pulmonaire pourraient être associées aux niveaux de E2 foetal. La 17ßHSD2 placentaire pourrait alors réguler E2 foetal et maternel. Cette étude établit s’il existe une corrélation entre E2 foetal et la 17βHSD2 pulmonaire et compare les ratios (E2 foetal/ E2 maternel) avec l’expression de la 17βHSD2 placentaire. E2 fut dosé par spectrométrie de masse et l’ARNm de la 17βHSD2 fut mesuré par QPCR. Aucune corrélation entre E2 foetal et la 17ßHSD2 pulmonaire n’existe. Les ratios de E2 ne corrèlent pas avec la 17ßHSD2 placentaire. Ces résultats suggèrent un contrôle local de la 17ßHSD2 dans les poumons foetaux tandis que les ratios E2 pourraient être régulés par la 17βHSD1 placentaire.
Estradiol (E2) exerts a positive effect on fetal lung maturation. The 17 beta-hydroxysteroid dehydrogenase type 2 (17ßHSD2) inactivates estrogens and androgens. 17ßHSD2 also presents a peak and an inter-litter variation of expression at gestational day 17.5 in the murine fetal lung. The variability of the pulmonary 17ßHSD2 mRNA levels could be explained by variations in fetal E2 levels. The placental 17ßHSD2 could regulate fetal and maternal E2. This study determined if a correlation exists between fetal E2 levels and pulmonary 17βHSD2 mRNA levels. A comparison was also made between E2 ratios (fetal / maternal) and the placental 17βHSD2 mRNA levels. E2 was measured by gas chromatography-mass spectrometry and 17βHSD2 was determined by quantitative PCR. There is no correlation between levels of fetal E2 and pulmonary 17ßHSD2 mRNA. Ratios of E2 levels do not correlate with placental 17ßHSD2 mRNA. These results suggest a local control of 17ßHSD2 mRNA levels in fetal lungs. Ratios of E2 could be regulated by the placental 17βHSD1.

La naissance est une période à risque qui met en jeux de multiples mécanismes qui permettent une transition de la vie fœtale et la vie extra-utérine. Chaque année, dans les conséquences d'une mauvaise adaptation à la vie extra-utérine et la persistance de résistances vasculaires pulmonaires trop élevées, 1 million de nouveau-né décède dans les 24 premières heures de vie. Dix pourcents des nouveau-nés requièrent une assistance médicale en salle de naissance. Le clampage du cordon ombilical retardé entre 60 et 180 secondes après la naissance est désormais recommandé pour toutes les situations où le nouveau-né, à terme comme prématuré, s'adapte bien à son nouvel environnement diminuant entre autres, le risque d'anémie ferriprive des premiers mois de vie. La hernie de coupole diaphragmatique (HCD) est une malformation cardio-pulmonaire secondaire à un défaut de fermeture du muscle diaphragmatique. Elle entraine une mortalité élevée et responsable d'un trouble de l'adaptation à la vie extra-utérine. Dans les situations de réanimation en salle de naissance, du fait du manque de données physiologiques et cliniques, il n'est pas encore recommandé de maintenir les échanges fœto-placentaires en parallèle de l'initiation de la réanimation. Dans ce travail de thèse, nous posons l'hypothèse que le placenta puisse participer à l'oxygénation et à la décarboxylation du nouveau-né le temps que la circulation cardio-pulmonaire du nouveau-né se mette en place. Le but de ce travail est d'étudier la physiologie de l'hémodynamique et des échanges gazeux transplacentaires lors d'une réanimation à cordon intact (RCI) dans un modèle d'agneau sain et dans un modèle d'agneau porteur de hernie diaphragmatique. Les objectifs étaient (1) de présenter l'étude clinique « CHIC » évaluant l'impact de la RCI chez le nouveau-né porteur de HCD, (2) mettre en place le modèle expérimental d'agneau HCD, (3) explorer la faisabilité et la durée maximale d'une réanimation à cordon intact chez l'agneau, (4) étudier l'évolution de l'hémodynamique et des échanges gazeux transplacentaires au cours d'une RCI dans un modèle d'agneau sain et porteur d'une HCD. Nous avons démontré que l'hémodynamique fœto-placentaire pouvait était stable (débits veineux ombilicaux, résistances vasculaire transplacentaires) jusque 1 heure après la mise en place d'une RCI. Dans un modèle d'agneau hernie diaphragmatique, où l'échangeur pulmonaire ne permet pas d'assurer normalement une augmentation rapide de la pression partielle artérielle en oxygène (PaO2), le placenta permettait d'assurer une oxygénation et une décarboxylation tout au long de la réanimation avec un apport en oxygène par le placenta stable pendant 1 heure (2,7 [2,2-3,3] ml/kg/min). A l'inverse, dans un modèle physiologique, le maintien d'une circulation placentaire est associé à une diminution de la pression artérielle systémique de l'ordre de 20% comparée au groupe hernie diaphragmatique (p<0,05). L'augmentation de la PaO2 dans ce groupe est associée avec une diminution des apports en oxygène par le placenta. Le clampage du cordon entraine dans ce groupe une élévation de la PaO2 et une diminution de la capnie. L'ensemble de ces travaux apporte une base physiologique essentielle à la pratique d'une réanimation à cordon intact et souligne l'importance de stratégies de réanimation individualisées en fonction des conditions cliniques spécifiques
Birth is a critical period during which numerous mechanisms are engaged to enable the transition from fetal to extrauterine life. Each year, due to poor adaptation to this transition and the persistence of elevated pulmonary vascular resistance, 1 million newborns die within the first 24 hours of life. Ten percent of newborns require medical assistance in the delivery room. Delayed umbilical cord clamping, between 60 and 180 seconds after birth, is now recommended in all situations where the newborn, whether full-term or premature, adapts well to the new environment. This practice notably reduces the risk of iron deficiency anemia in the first months of life.Congenital diaphragmatic hernia (CDH) is a cardiopulmonary malformation caused by a defect in the closure of the diaphragm, leading to high mortality and impairing adaptation to extrauterine life. In delivery room resuscitation scenarios, the lack of physiological and clinical data has not yet allowed for the recommendation of maintaining feto-placental circulation alongside the initiation of resuscitation.In this thesis, we hypothesize that the placenta could contribute to oxygenation and decarboxylation of the newborn until the cardio-pulmonary circulation is established. The aim of this work is to study the physiology of hemodynamics and transplacental gas exchange during intact cord resuscitation (ICR) in a healthy lamb model and in a lamb model with CDH. The specific objectives were: (1) to present the clinical study “CHIC” evaluating the impact of ICR in newborns with CDH; (2) to establish an experimental lamb model of congenital diaphragmatic hernia; (3) to explore the feasibility and maximum duration of intact cord resuscitation in this model; and (4) to study the evolution of hemodynamics and transplacental gas exchange during ICR in both healthy and CDH lamb models.We demonstrated that feto-placental hemodynamics (umbilical venous flow, transplacental vascular resistance) remained stable up to one hour after the initiation of ICR. In the lamb model with diaphragmatic hernia, where the pulmonary exchange system cannot adequately increase arterial partial oxygen pressure (PaO2), the placenta provided sufficient oxygenation and decarboxylation throughout the resuscitation, with stable placental oxygen delivery for one hour (2.7 [2.2-3.3] ml/kg/min). Conversely, in the physiological model, maintaining placental circulation was associated with a 20% decrease in systemic arterial pressure compared to the CDH group (p<0.05). The increase in PaO2 in this group was associated with a decrease in placental oxygen delivery. Cord clamping in this group led to an increase in PaO2 and a decrease in carbon dioxide levels. These findings provide an essential physiological basis for the practice of intact cord resuscitation and highlight the importance of individualized resuscitation strategies based on specific clinical conditions

Le placenta est un organe provisoire joignant la mère et le fœtus qui transfère l’oxygène et des nutriments de la mère au fœtus et permet l’évacuation de l’anhydride carbonique et des produits du métabolisme du fœtus. Le but de notre travail était d’étudier la fonction de transfert des tissus placentaires selon son développement en se basant sur les images ultrasonores. Nous avons développé au cours de ce travail une nouvelle approche de la classification du développement placentaire en ultrasons par des techniques de traitement d’images avancées basée sur une représentation par réseau neuronal. Le modèle réalisé par la transformée en ondelettes basé sur le réseau neuronal MLP représente donc un outil efficace et rapide répondant à nos critères et bien adapté à nos applications concernant l’étude de la maturation placentaire. L’application du modèle réalisée en cas de traitement d’images placentaires ouvre des portes intéressantes en terme de classification des grades placentaires afin d’identifier des stades de maturation autorisant la définition d’une maturation normale et de classes à risque
The placenta is a temporary organ joins the mother and the fœtus, which transfers oxygen from the mother to the foetus, allows the evacuation of the carbon dioxide and the products of foetus metabolism. The goal of our work is to study the transfer function of placental development using ultrasound images. A new approach is developed during this work to classify the placental development by image processing techniques based on supervised neural network. The realized model by the wavelet transform based on MLP neural network, represents an effective tool answering our criteria and adapted to our applications concerning the study of placental maturation. The realized model application in the event of placental image processing opens interesting doors in terms of placental grades classification in order to identify the stages of maturation, authorizing the definition of a normal maturation and an abnormal maturation

These studies have quantified human placental development throughout 10-41 weeks of `normal' gestation, and compared the structure of term organs delivered at low (400m) and high (3600m) altitudes in Bolivia. Quantitative analyses of histological preparations were performed using stereological techniques. Salient structural parameters were then combined with physicochemical constants (gleaned from the literature) to estimate the oxygen conductances of the maternal and fetal erythrocytes and plasmas, the trophoblast and the stroma. These were combined to yield Dp, the total morphometric diffusing capacity for oxygen (in ml O₂/min/torr). During the third trimester, villous trees expand predominantly by the elaboration of terminal villi. This increases the surface areas and decreases the thicknesses of the trophoblast and the stroma (the two compartments which offer the greatest resistance to oxygen diffusion). The sources of expansion of the villous trees may lie in the transformation of immature intermediate villi into stem and mature intermediate villi. Hypoxically stimulated capillary elongation within mature intermediate villi may be involved in initiating the production of new terminal villi. It is interesting that the total length and surface area of terminal villi were maintained in highland organs while those of larger diameter villi were significantly lower than in lowland controls. Total villous surface area was significantly reduced in highland organs while capillary surface was comparable to lowland estimates. However, reductions in harmonic mean trophoblast and stromal thicknesses helped to conserve the conductance of the trophoblast and to increase that of the stroma above lowland values. Dp increased significantly but specific Dp remained constant throughout gestation. Although the main stressor at high altitude is hypobaric hypoxia, no significant altitudinal differences in Dp were found. The intrauterine growth retardation consistently observed and high altitudes therefore occurs despite placental adaptations which maintain Dp at lowland values.