A Preliminary Study Of The Environmental Endocrine Disruptors In The Role Of The Polycystic Ovary Syndrome

[Abstract] Objective Valproate (VPA) is widely used to treat epilepsy. Long-term treatment of women with VPA has been reported to be associated with a PCOS-like syndrome. The aim of the present study was to investigate the effects of clinically relevant concentrations of valproate on steroidogenesis and steroidogenesis acute regulatory protein (StAR) , cholesterol side-chain cleavage enzyme (P450scc)and cytochrome P450 aromatase (P450arom) mRNA expression in human luteinized granulosa cells in vitro. Methods Human luteinized granulosa cells were collected from oocyte retrieval of in vitro fertilization procedure and were cultured with DMEM medium and treated various concentration of valproate (0, 100, 250mg/L), the culture media were collected after 2 days for progesterone and estradiol measurements by standard radiommunoassay, StAR, P450scc and P450arom mRNA in granulosa cells were detected by fluorescent real-time RT-PCR (TaqMan?assay). Results Valproate caused a significant increase of progesterone (P<0.05) and estradiol(P<0.001) production , and significantly increased StAR (P<0.01). P450scc(P<0.05) and P450arom (P<0.001) mRNA expression were observed in cultured cells. Conclusions valproate directly altered steroidogenesis of steroidogenesis cells: valproate increased progesterone and estradiol secretion by inducing StAR. P450scc and P450arom mRNA expression in human luteinized granulosa cell. And the occurrence of polycystic ovaries and endocrine disorders in women taking valproate for epilepsy may be attributed to valproate itself. It also implies that environmental chemicals may be related to the pathogenesis of PCOS.