Cellular and molecular mechanisms mediating the effect of polychlorinated biphenyls on oocyte in vitro maturation

Department of Anatomy of Domestic Animals, University of Milano, 20133 Milano, Italy.
Reproductive Toxicology (Impact Factor: 3.23). 09/2006; 22(2):242-9. DOI: 10.1016/j.reprotox.2006.04.023
Source: PubMed


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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    • "Disruption of this finely tuned (endocrine/paracrine) balance can lead to anovulation (Mumford et al., 2011), cystic deformation (Baptiste et al., 2010) or a diminished oocyte quality which jeopardizes further embryo development (Leroy et al., 2005). Although in vitro experiments suggest a role for EDCs in disturbing the tightly regulated endocrine and paracrine signaling in the different cells of the ovarian follicle (Brevini et al., 2004; Pocar et al., 2006; Kwintkiewicz et al., 2010), these exposure experiments can only be related to the in vivo situation if environmental relevant EDC concentrations are considered. Moreover, almost no in vivo data are currently available about the association of a women's IVF record and the presence of EDCs in her follicular fluid, i.e. the in vivo micro-environment in which the female gamete grows and matures. "
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    ABSTRACT: Throughout the previous century, the production, use and, as a result, presence of chemicals in the environment increased enormously. Consequently, humans and animals are exposed to a wide variety of chemical substances of which some possess the ability to disrupt the endocrine system in the body, thereby denominated as "endocrine disrupting chemicals" (EDCs) or "endocrine disruptors". Because the reproductive system is a target organ for endocrine disruption, EDCs are postulated as one of the possible causes of human subfertility. Within the reproductive system, the ovarian follicle can be considered as an extremely fragile microenvironment where interactions between the oocyte and its surrounding somatic cells are essential to generate a fully competent oocyte. In this review, we explore how EDCs can interfere with the well-balanced conditions in the ovarian follicle. In addition, we highlight the bovine ovarian follicle as an alternative in vitro model for EDC and broader toxicology research.
    Theriogenology 08/2012; 78(9). DOI:10.1016/j.theriogenology.2012.06.011 · 1.80 Impact Factor
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    • "Organochlorine compounds have been associated with altered endocrine function, reduced fertility, and early pregnancy loss in experimental animals [9,10] and limited human studies [11-13], but more research is needed to understand potential risks associated with human exposure. An important limiting factor in assessing risk based on human studies is the degree of measurement error associated with the exposure estimate(s) used in a particular study. "
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    ABSTRACT: Exposure to persistent organic pollutants, including polychlorinated biphenyls (PCBs) and organochlorine pesticides, is widespread among the general population. There is evidence of adverse effects on reproduction and early pregnancy in relation to organochlorine exposure but human studies remain limited. The increased use of assisted reproductive technologies (ART) presents unique opportunities for the assessment of environmental influences on early pregnancy outcomes not otherwise observable in humans, but studies need to be designed to maximize the efficiency of the exposure data collected while minimizing exposure measurement error. The present study was conducted to assess the correlation between concentrations of organochlorines in serum and follicular fluid samples collected from a subset of women undergoing ART in a large study that took place between 1994 and 2003, as well as the temporal reliability of serum organochlorine concentrations among women undergoing multiple ART cycles in the study. PCB congeners (118, 138, 153, and 180), 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (p,p'-DDT), the DDT metabolite p,p'-DDE, hexachlorobenzene (HCB), oxychlordane, trans-nonachlor and mirex were measured in 72 follicular fluid samples and 265 serum samples collected from 110 women. Organochlorine concentrations in paired serum and follicular fluid samples were correlated, with Pearson and Spearman coefficients ranging from 0.60 to 0.92. Serum organochlorine concentrations were two- to three-fold greater than in follicular fluid, and a significant inverse trend was observed in the distribution of follicular fluid:serum ratios with increasing molecular weight of the compound (p-value for trend < 0.0001). Serum organochlorine concentrations were highly reliable over the course of several months, with intraclass correlation coefficients ranging from 0.86 to 0.98. Finally, there was evidence for a declining trend in organochlorine concentrations between samples collected between years 1994-1998 and those collected in 1999-2003. Our results support the use of a single serum sample to adequately represent a more biologically relevant dose (concentrations in follicular fluid), as well as exposure levels over time, in epidemiological studies of ART outcomes in relation to organochlorine exposure.
    Environmental Health 07/2009; 8(1):32. DOI:10.1186/1476-069X-8-32 · 3.37 Impact Factor
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    • "Prominent among these environmental estrogens are the PCBs (Ulbrich and Stahlmann, 2004). PCBs are a group of the halogenated aromatic hydrocarbons which are among the most persistent and widespread environmental estrogens (Safe, 1994; Pocar et al., 2006). Because of their chemical stability, lipophilic property and resistance to degradation, PCBs are making their way into all levels of food chain and preferentially bioaccumulate and biomagnify in wildlife as well as humans (McFarland and Clarke, 1989; Buckman et al., 2006). "
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    ABSTRACT: Cytosolic sulfotransferases (SULTs) constitute a family of Phase II detoxification enzymes that are involved in the protection against potentially harmful xenobiotics as well as the regulation and homeostasis of endogenous compounds. Compared with humans and rodents, the zebrafish serves as an excellent model for studying the role of SULTs in the detoxification of environmental pollutants including environmental estrogens. By searching the expressed sequence tag database, two zebrafish cDNAs encoding putative SULTs were identified. Sequence analysis indicated that these two putative zebrafish SULTs belong to the SULT1 gene family. The recombinant form of these two novel zebrafish SULTs, designated SULT1 ST7 and SULT1 ST8, were expressed using the pGEX-2TK glutathione S-transferase (GST) gene fusion system and purified from transformed BL21 (DE3) cells. Purified GST-fusion protein form of SULT1 ST7 and SULT1 ST8 exhibited strong sulfating activities toward environmental estrogens, particularly hydroxylated polychlorinated biphenyls (PCBs), among various endogenous and xenobiotic compounds tested as substrates. pH-dependence experiments showed that SULT1 ST7 and SULT1 ST8 displayed pH optima at 6.5 and 8.0, respectively. Kinetic parameters of the two enzymes in catalyzing the sulfation of catechin and chlorogenic acid as well as 3-chloro-4-biphenylol were determined. Developmental expression experiments revealed distinct patterns of expression of SULT1 ST7 and SULT1 ST8 during embryonic development and throughout the larval stage onto maturity.
    Aquatic Toxicology 08/2008; 89(2):94-102. DOI:10.1016/j.aquatox.2008.06.005 · 3.45 Impact Factor
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