Cellular and molecular mechanisms mediating the effect of polychlorinated biphenyls on oocyte in vitro maturation.
ABSTRACT Cellular and molecular mechanisms mediating the effect of polychlorinated biphenyls on oocyte in vitro maturation: Polychlorinated biphenyls (PCBs) are stable, lipophilic compounds that accumulate in the environment and in the food chain. Recent studies provide evidence that exposure to PCBs can cause reproductive problems. PCBs have been identified in the ovarian follicle of women and other mammals and many data in the literature clearly indicate that both follicles and oocytes are particularly susceptible to these pollutants. In the present review we describe the multifaceted effects of PCBs on mammalian oocyte maturation in detail. Published studies clearly indicate that PCB congeners, both singly or as complex mixtures, disrupt mammalian oocyte maturation and subsequent embryo development. Specifically, data point out to the ability of PCBs to interfere with the organization of the microtubules cytoplasmic network resulting in an altered compartmentalization of the ooplasm. Furthermore, a critical role of cumulus cells in mediating PCB ovotoxicity has been observed, most likely related to a disregulation in intracellular communication between the germinal and the somatic compartment. Finally, since coplanar PCBs, induce gene expression via a ligand-dependent transactivating factor, the aryl hydrocarbon receptor, this signalling pathway is also reviewed with respect to understanding the toxic mechanisms of these compounds.
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ABSTRACT: Polychlorinated biphenyls (PCBs) are stable, lipophilic compounds that accumulate in the environment and in the food chain. Though some studies provided evidence that PCBs had adverse effects on reproductive function, most of these results were from in vitro models. Therefore we investigated the effect of Aroclor 1254 (a commercial PCBs mixture) treatments on in vivo maturation and developmental potential of mouse oocytes. In the present study, female ICR mice were treated with different doses (12.5, 25 and 50 mg/kg) of Aroclor 1254 (a commercial PCB mixture) once every 72 hours by intraperitoneal injection for 9 days. After three treatments of Aroclor 1254, the mice were superovulated to collect oocytes one day after the last exposure. The effects of Aroclor 1254 on oocyte maturation, fertilization, and preimplantation embryonic development were investigated. Immunofluorescence-stained oocytes were observed under a confocal microscope to assess the effects of Aroclor 1254 on spindle morphology. Parthenogenic activation and the incidence of cumulus apoptosis in cumulus-oocyte complexes were observed as well. Oocytes exposed to different doses of Aroclor 1254 in vivo were associated with a significant decrease in outgrowth potential, abnormal spindle configurations, and the inhibition of parthenogenetic activation of ovulated oocytes. Furthermore, the incidence of apoptosis in cumulus cells was increased after exposed to Aroclor 1254. These results may provide reference for the treatment of reproductive diseases such as infertility or miscarriage caused by environmental contaminants.PLoS ONE 01/2014; 9(7):e102064. · 3.73 Impact Factor
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ABSTRACT: Increased global industrial activity has exposed humans to a wide variety of chemical substances some of which, called 'endocrine-disrupting chemicals' (EDCs) or 'endocrine disruptors', can disrupt the endocrine system in the body. The ovarian follicle is a very fragile micro-environment where interactions between hormones, growth factors, the oocyte and its surrounding somatic cells are essential to generate a fully competent oocyte. In vitro experiments suggest that EDCs can disturb this finely tuned balance, but very scarse in vivo data are available to confirm this assumption. Therefore, we have investigated if the presence of EDCs in human follicular fluid is a risk factor for the developmental competence of an in vivo exposed oocyte. Furthermore, because of the limited access to human follicular fluid, we verified if follicular fluid contamination can be predicted based on EDC levels in serum. Follicular fluid (n = 40) and serum (n = 20) samples from women undergoing assisted reproductive technology (ART) were analyzed by means of gas chromatography combined with mass spectrometry to examine the presence of different EDCs, such as polychlorinated biphenyls, polybrominated diphenyl ethers and organochlorine pesticides. Statistical models were used to investigate the relation between the characteristics and ART results of the patients and the contamination status of their follicular fluid and to assess the capacity of serum samples to predict follicular fluid contamination. Chlorinated biphenyl 153 (72 ± 44 and 201 ± 106 pg/ml) and p,p'-DDE (392 ± 348 and 622 ± 406 pg/ml) were the compounds found in the highest concentrations in follicular fluid and serum samples, respectively. A new variable principal component 1, representing the overall contamination status of the follicular fluid samples, is strongly associated with fertilization rate (P < 0.00001) and the proportion of high-quality embryos relative to the amount of retrieved oocytes (P < 0.05), even when the analysis is adjusted for age, estradiol concentration, BMI, fertilization procedure and male subfertility as explanatory variables. The strong correlations between the EDC concentrations in serum and follicular fluid (r ≥ 0.93) allowed us to build regression models, which accurately predict EDC concentrations in the follicular fluid based on serum samples. An overall higher EDC contamination in the follicular micro-environment was associated with a decreased fertilization rate and consequently with a lower chance of an oocyte to develop into a high-quality embryo. In addition, EDC concentrations in serum were reliable predictors of the contamination status of the follicular micro-environment.Human Reproduction 01/2012; 27(4):1025-33. · 4.67 Impact Factor
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ABSTRACT: Abstract In recent years, zebrafish has emerged as a useful animal model for biomedical research. The deciphering of the zebrafish genome has revealed that many of the enzymes involved in the metabolism of endogenous compounds and xenobiotics are conserved between zebrafish and humans. This review summarizes the information currently available concerning the zebrafish cytosolic sulfotransferases (SULTs), a group of phase II enzymes that have been proposed to be involved in the regulation and homeostasis of key endogenous compounds and the detoxification of xenobiotics. To date, 20 zebrafish SULTs that fall into six major SULT gene families have been identified. Of the 20 SULTs 18 have been cloned, expressed, purified and characterized. These zebrafish SULTs were shown to exhibit differential substrate specificities for endogenous compounds such as monoamine transmitters, steroid/thyroid hormones and bile salts, as well as xenobiotics including environmental toxicants and drugs. These findings provide a foundation for using zebrafish as a model for investigating further the physiological, pharmacological, and toxicological involvement of the SULTs.Drug Metabolism Reviews 09/2013; · 5.54 Impact Factor