EFFECT OF ENDOCRINE DISRUPTING CHEMICALS ON GERMINAL VESICLE BREAKDOWN IN XENOPUS IN VITRO*

Abstract

ABSTRACTCurrently, 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/anti-progestin 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 Gt; EGME>EE>Cd>B. Although EE was more effective in inhibiting GVBD, EGME appeared to bind more tightly to the OMPR.