Literatura académica sobre el tema "Repro-toxicity"

Human reproduction and development is a cycle of interdependent events. Virtually all of its phases have been shown to be the primary target of one or more non-mutagenic exogenous agents (Table 1). Such agents interfere with certain of the countless epigenetic or ontogenic events essential for normal completion of the cycle. Mutagens disrupt this cycle at some points, but the overwhelming majority of reproduc tive and developmental toxins are not mutagenic. As in all aspects of toxicology, the reproductive and developmental effects of chemicals are determined by the intrinsic nature of the chemical, the quantity of the chemical exposure, the duration of exposure and the stage of the cycle at which it occurs. Signs of repro ductive toxicity range from reduced fertility to spontaneous abortion. Adverse effects on the conceptus are categorized as functional deficits, developmental retardation, structural abnormality and death. One or more of these is anticipated to occur as a result of excess exposure to most chemicals. Although the degree of hazard and risk potential can be calculated in each instance, chemicals differ markedly in their ability to interfere with reproduction (Amann, 1982) and/or develop ment (Johnson, 1984). Standardized methods for reproductive and developmental toxicity safety evaluation are available for detecting adverse effects upon any

Abstract Subtidal sediments were collected in Halifax Harbour, Nova Scotia, in July and August, 1992, to study sediment toxicity and hazards near the proposed location of a sewage treatment plant and outfall. A set of 110 samples from eight stations was evaluated. Interstitial water from surface (0-2 cm) and subsurface (2-4 cm) sediments was analyzed by the Microtox® 100% toxicity test protocol. The sediment particles were analyzed using the Microtox® solid-phase test. Interstitial water from surface and subsurface sediments from all stations was usually non-toxic, compared to a phenol standard. The mean 5 min-EC50 of surface sediments (n=57) was 5,433mg/L; the mean 5 min-EC50 of subsurface sediments (n=50) was 804 mg/L. Toxicity thresholds for the harbour sediments were compared with National Research Council marine analytical sediment reference materials and a selection of natural sediments, and ranked. An experiment with the marine reference sediments (certified for PAHs and trace metals) and their mixtures showed the ability of the solid-phase test to discriminate among different levels of contaminated sediments. Intra- and inter-sample variability in toxicity at different locations in relation to time, sediment depth, sediment properties, and types and concentrations of contaminants was evaluated by multivariate and PCA tech-niques. This laboratory-field study provided insights into the sensitivity, repro-ducibility, significance and discriminatory ability of the Microtox® solid-phase bioassay and its value in the study of complex natural sediment mixtures.

1 Reproductive toxicity and toxicokinetics of lindane during lactation were studied. For the reproductive toxicity study the dams were treated with a single dose of 6 mg/kg on day 9 or 14 of lactation, or with 1 mg/kg on days 9 to 14 of lactation. The male offspring were investigated at puberty and adulthood. For the toxicokinetic study, two groups of dams were treated with 6 mg/kg on day 9 or 14 of lactation. The concentration of lindane was measured in maternal plasma and milk, as well as in male offspring organs. 2 At adulthood, testicular weight and the number of sperm and spermatids were significantly reduced in all treated groups. 3 The testosterone level of the groups treated with 6 mg/ kg was significantly reduced to approximately 50% at puberty as well as in adulthood. In the group treated with 1 mg/kg, the testosterone level was in both age periods reduced, however, only at puberty was the reduction statistically significant. 4 The concentration oflindane in the testis was similar to that found in brain and was half the concentration found in the liver. 5 Histologically some areas of the testis exhibited distinct alterations ranging from small changes to a pronounced effect. 6 Exposure to lindane during lactation induces repro ductive hazards to male offspring rats which are detectable at adulthood.

1 Carbofuran was administered orally to adult male rats at dose levels of 0.1, 0.2, 0.4 or 0.8 mg kg -1 body weight, 5 d wk-1 for 60 days. A dose dependent decrease was observed in body weight of rats treated with 0.2-0.8 mg carbofuran kg -1 body weight 2 A significant decrease in the weight of epididymides, seminal vesicles, ventral prostate and coagulating glands was observed at various test doses of carbofuran except at the lowest dose. 3 Decreased sperm motility, reduced epididymal sperm count along with increased morphological abnormali ties in head, neck and tail regions of spermatozoa were observed in rats exposed to 0.2, 0.4, or 0.8 mg carbo furan kg-1 body weight. 4 In addition, significant alterations were observed in the activities of marker testicular enzymes viz. sorbitol dehydrogenase (SDH), glucose-6-P-dehydrogenase (G6PDH) (decreased), lactate dehydrogenase (LDH) and γ-glutamyl transpeptidase (γ-GT) (increased) depending on dose. 5 Histologically, the results indicated the toxicity of carbo furan on testes depending on dose. The changes pre dominantly consisted of moderate oedema, congestion, damage to Sertoli cells and germ cells, along with the accumulation of cellular debris and presence of giant cells in the lumen of a few seminiferous tubules which showed disturbed spermatogenesis with the higher doses of carbofuran. 6 These observations determined a no effect level dose of 0.1 mg kg-1 body weight of carbofuran on the biochemi cal and morphological indices studied for male repro ductive toxicity assessment in the rat model. The results of the present study provide first hand information on the reproductive toxicity of carbofuran in male rats.

Background: The heavy metals cause repro-toxicity via oxidative stress and suppress the antioxidant enzymes. Kaempferol and vitamin E possess antioxidant properties that can counteract the deleterious heavy metals effects. Aim: The present study was directed to investigate the protective role of kaempferol, alone or with vitamin E, on testicular toxicity mediated by lead acetate in male rats. Methods: Fifty adult male rats were randomly grouped into five groups (n=10): the control group received 5ml distilled water, and the Pb group was I.P injected with 20 mg/kg of lead acetate. Pb + Vit. E group received Pb with 100 mg/kg of vitamin E, Pb + KAF group received Pb with 50 mg/kg of kaempferol, Pb + KAF + Vit. E group received Pb with kaempferol and vitamin E for six weeks. Results: The testicular levels of superoxide dismutase, catalase, steroidogenic enzyme, serum testosterone, FSH, interleukin -10, and sperm function were significantly decreased in the Pb group compared with all experimental groups. These parameters were significantly elevated in Pb + KAF + Vit. E group compared to other experimental groups. Lead acetate caused elevation in testicular malondialdehyde, nitric oxide, interleukin-6, interleukin-1β, tumor necrosis factor-α, nuclear factor kappa, and sperm abnormality compared to all treatment groups. All these parameters were significantly declined in the Pb + KAF + Vit. E group and Pb + KAF group compared with the Pb group. The fold changes of pituitary FSHβ, GnRHr, and LHβ, and testicular CYP11A1, LHr, and FHr gene expression were significantly upregulated in Pb + KAF + Vit. E group compared with all experimental groups. Additionally, KAF + Vit. E have the potential to improve the testicular regeneration in seminiferous tubules, Leydig, and Sertoli cells. Conclusion: Administration of kaempferol alone or with vitamin E can mitigate lead acetate-induced testicular toxicity in rats via its antioxidant and anti-inflammatory properties. The current research is the first to demonstrate that kaempferol can exert a preventive role in testicular dysfunction.

Abstract The goal of this study is to examine BPAF-induced multinucleation (MNC) in comparison with di-butyl phthalate (DBP), known to induce MNC in mouse gonocytes in vivo. We performed image-based single-cell high content analysis (HCA) in the mouse spermatogonia C18-4 cells treated with various concentrations of BPAF and DBP. BPAF as low as 5 µM was cytotoxic and resulted in 40% cell death of the C18-4 cells after 72h. HCA revealed that 5 µM of BPAF significantly increased the number of MNC by an average of 3.6-fold. DBP did not induce MNC in the doses we tested. Cytokinesis is tightly regulated by various small GTPase- signaling pathways. We, therefore, tested five selective GTPase inhibitors and found that Y27632, a ROCK inhibitor, reduced the BPAF-induced MNC by nearly 30%. Inhibition of Cdc42 by ML141 conversely increased the number of BPAF-induced MNC. We performed a hierarchical cluster analysis of the HCA data and demonstrated that the cytoskeletal disruption by BPAF was reversely modified by Y27632. We found that mRNA expression of genes regulating Rho and Rac GTPase activities, p190RhoGap and MgcRacGap, were altered in BPAF-treated C18-4 cells in a time-dependent manner. Multinucleated gonocytes are often indicators of disease pathologies. Our results provided the first evidence of mechanisms of the dual toxicity by BPAF to male germ cells, which induces chromosome endoreplication without the coordinated cytokinetic cellular components. The unique genotoxic mechanism of forming multinucleated germ cells suggests a novel mode of action in the male repro-toxicity concern over the increasingly ubiquitous presence of BPA analogs.

AbstractThe male reproductive system is negatively influenced by Al exposure. Al represented a considerable hazard to men’s reproduction capabilities. Amygdalin (AMG) and spirulina platensis (SP) have been considered to have a strong antioxidant and repro-protective activity; also, targeted drug delivery systems called niosomes improve the distribution of water-soluble medications like amygdalin and spirulina. Current study targeted to determine the effectiveness of AMG and SP against negative reproductive impact resulted by aluminum chloride (AlCl3) toxicity. Sixty adult male albino rats were separated into 6 groups, including the control group, which received distilled water; AlCl3 group, which received AlCl3; AMG+AlCl3 group, which received AlCl3+AMG; AMGLN+AlCl3 group, which received AlCl3+amygdalin-loaded niosomes; SP+AlCl3 group, which received AlCl3+SP; and SPLN+AlCl3 group, which received AlCl3+spirulina-loaded niosomes. All treatments were orally gavaged daily for 5 weeks, and rats were weighed weekly. At the termination of the experiment, some males (three from each group) were used for fertility traits via mating thirty virgin rat females (in a ratio of 1:2 and 2:3 male:female, respectively) followed by recording of birth weights and litter size (number of pups per each female) at birth to assess males’ reproductive capability. Other males were euthanized for collection of serum, epididymal semen samples, and tissue samples for biochemical, sperm evaluation, gene expression, and histopathological measurements. There are a considerable number of negative impacts of AlCl3 on male fertility clarified by declined serum testosterone levels; an increased oxidative stress (MDA, TAC); deteriorated semen quality; down-regulation of CYP11A1, StAR, and HSD-3b gene expressions; and testicular tissue degenerative changes. In addition, litter size (number of pups per each female) and birth weights of pups obtained from mated females were affected. AMG and SP treatments, either in niosomal or conventional form, alleviated the AlCl3 negative effects by reducing oxidative stress; increasing testosterone levels; improving semen quality; upregulating of CYP11A1, StAR, and HSD-3b gene expressions; and reducing degenerative changes of testicular tissue. Besides, negative reproductive effect was diminished as observed by changes in the litter size (number of pups per each female) and birth weights of pups obtained from mated females. AMG and SP treatments (either in niosomal or conventional form), ameliorated the AlCl3 negative effects as they possess powerful antioxidant activity, as well as they have the ability to improve the reproductive activity of affected males. Graphical abstract

Les troubles de la fertilité représentent un enjeu majeur de santé publique puisqu’ils concernent des millions de personnes en âge de procréer à travers le monde. Le facteur masculin intervient dans 50% des cas identifiés d’infertilité du couple, impliquant des anomalies qualitatives et/ou quantitatives de la production spermatique. Cependant à l’heure actuelle, l’origine d’une grande partie des troubles de la reproduction masculine demeure inexpliquée. Depuis plusieurs décennies le monde constate une augmentation de ces troubles, plus particulièrement dans les pays développés, attirant ainsi l’attention de la communauté scientifique sur l’implication des polluants environnementaux dans l’étiologie de l’infertilité. Le nombre et la diversité des polluants xénobiotiques relargués dans la nature sont colossaux et menacent de nombreuses fonctions physiologiques dont la reproduction, en raison de leurs capacités d’interaction avec de multiples voies de signalisations. Selon les chercheurs, l’exposition périnatale aux xénobiotiques peut altérer la physiologie testiculaire et prédisposer au développement de troubles de la fertilité. Néanmoins, une meilleure compréhension des signalisations associées aux molécules environnementales et de leurs liens avec les physiopathologies testiculaires est essentielle afin d’identifier de nouvelles causes d’infertilité. Les récepteurs CAR et PXR sont des récepteurs de xénobiotiques exprimés dans le testicule chez l’Homme ainsi que chez le rongeur. Cependant leurs rôles au sein du testicule n’ont pas encore été entièrement établis. Dans cette étude, nous avons étudié les impacts sur la physiologie testiculaire et sur la fonction de reproduction des modulations néonatales de leur signalisation dans un modèle murin. Nos résultats montrent que l’inhibition de la signalisation CAR entraîne des troubles de la fertilité chez la souris, associés à des altérations qualitatives des spermatozoïdes. En effet, nous avons identifié des défauts au niveau des processus de différenciation précoce et tardif des cellules germinales impliquant notamment des dérégulations de la signalisation FOXO1 ainsi que des niveaux d’acétylation de l’histone H4pouvant être associées à une rétention des histones au sein du génome spermatique. De plus, nous avons également mis en évidence des impacts délétères additifs des activations néonatales des voies de signalisation CAR et PXR sur la fertilité des souris. Notre étude souligne les rôles majeurs des récepteurs nucléaires CAR et PXR dans la physiologie testiculaire ainsi que leur implication potentielle dans la survenue des troubles de la fertilité dans un contexte d’expositions environnementales
Fertility disorders are a major public health concern since they concern millions of people of reproductive age all over the world. The male factor is involved in 50% of identified cases of infertility within couples, involving qualitative and quantitative alterations of the sperm production. However, there are still too many unknowns regarding the cause of many male reproductive disorders. For several decades, an increase in these disorders has been detected especially in developed countries, attracting the scientific community attention to the involvement of environmental pollutants in the etiology of infertility. The number and variety of xenobiotics released into the environment are huge and threaten many physiological functions because of the multiple intracellular signalling pathways that they can affect. According to the researchers, perinatal exposure to xenobiotics may induce altered testicular physiology and predispose to the development of fertility disorders. However, It is essential to better understand the signalling pathways involved in the negative environmental impacts of xenobiotics on testicular physiology to identify other causes of infertility. CAR and PXR are xenobiotic receptors expressed in the testis in men as well as rodents. However, their roles within the testis have not been fully established. In this study, we have identified impacts of neonatal modulations of their signalling on the testicular physiology and the reproduction function in mice. Our data showed that the inhibition of CAR signalling leads to fertility disorders in mice, correlated with qualitative sperm production. Indeed, we have detected alterations in the early and late differentiations of germ cells, notably involving FOXO1 signalling and H4 acetylation levels deregulations that can be associated with histones retention within the sperm genome. Moreover, we have highlighted deleterious additive impacts of the neonatal co-activation of CAR and PXR signalling of mice fertility. Our study has identified major roles of CAR and PXR nuclear receptors in testicular physiology and their potential implication in the emergence of fertility disorders associated with environmental exposures