EFFECT OF ENDOCRINE DISRUPTING CHEMICALS ON GERMINAL VESICLE BREAKDOWN INXENOPUSIN VITRO*

Abstract

Currently, no standardized and well-validated alternative models exist for screening for progesterone-responsive endocrine disrupting chemicals (EDCs). Because of this, a rapid assay for evaluating progestin/antiprogestin activity using Xenopus oocyte germinal vesicle breakdown (GVBD) as a model was evaluated. Five compounds, including progesterone (P), ethinyl estradiol (EE), ethylene glycol monomethyl ether (EGME), cadmium (Cd), and boric acid (B) were used to validate the model on a preliminary basis. Each test material was tested for progestin/anti-progestin activity. The binding affinity of each test material to the oocyte plasma membrane receptor (OPMR) relative to progesterone was then determined. Results from the present studies suggested that both EE and EGME were capable of inhibiting GVBD in a concentration-dependent manner. Cd had a subtle inhibitory effect at high concentrations. B had no effect on GVBD even at concentrations of 100 mg B/L, and thus appears to have no EDC activity in this model. The binding capacity of the test substances to the OMPR relative to progesterone was low. Thus, the relative inhibitory potential of the test materials study was EE > EGME >> Cd > B. However, the relative binding affinity of the toxicants to the OMPR can be expressed as P >> EGME > EE > Cd > B. Although EE was more effective in inhibiting GVBD, EGME appeared to bind more tightly to the OMPR.

Environmental (anti-)androgenic chemicals affect germinal vesicle breakdown (GVBD) of Xenopus laevis oocytes in vitro

“…In term of effective concentrations of androgens, the sensitivity of GVBD test using Xenopus oocytes is comparable to these in vitro assays in the literature. Although Xenopus GVBD is very sensitive to androgenic chemicals, one chemical cannot be determined whether or not to have androgenic activity by alone Xenopus GVBD test because progestin chemicals can also induce Xenopus GVBD (Fort et al, 2002). Then, it is necessary to combine other specific methods when determine the androgenic activity of chemicals using Xenopus GVBD.…”

“…Numerous studies have described effects of EDCs on gonadal differentiation, the secondary sex characteristic development, and metamorphic process of amphibians (Crump et al, 2002;Hayes et al, 2002Hayes et al, , 2010Porter et al, 2011;Qin et al, 2003). Also, some of EDCs, such as ethinyl estradiol, atrazine, 2,4-dichlorophenoxyacetic acid and methoxychlor, have been shown to affect oocyte maturation in amphibians, suggesting potential adverse effects on reproductive function of amphibians (Fort et al, 2002;Ghodageri and Katti, 2013;Pickford and Morris, 1999;Stebbins-Boaz et al, 2004). Given that androgens can induce oocyte maturation and anti-androgen flutamide can inhibit androgen-induced oocyte maturation, we propose that environmental androgens and anti-androgens could disrupt oocyte maturation of amphibians.…”

Effects of BPA and DES on longchin goby (Chasmichthys dolichognathus) in vitro during the oocyte maturation

“…This assay also tested the estrogenic EDC BPA, which had no observable effect on GVBD. Fort et al (2002) also demonstrated the inhibitory effects of EDCs, such as ethinylestradiol, Xenopus oocyte maturation. Similarly, the xenoestrogenic inhibition of progestin-induced GVBD has been demonstrated in fish oocytes, in Atlantic croaker, M. undulates, (Ghosh and Thomas, 1995).…”

In vitro assessment of reproductive toxicity of cigarette smoke and deleterious consequences of maternal exposure to its constituents

“…A prior study also showed that B[a] P induced inhibition of antral follicle development (Sadeu & Foster, 2010). Cadmium has been demonstrated to hinder germinal vesicle breakdown (Fort et al, 2002) and to reduce the percentage of oocytes undergoing normal developmental progression in vivo (Lienesch, Dumont & Bantle, 2000). Interestingly, B[a]P is detected in concentration ranging from 20 to 79ng per cigarette in SS and MS (Kaiserman & Rickert, 1992) and 50-200ng of cadmium is estimated to be inhaled when cigarette is smoked (Elinder, 1985).…”