A pilot study on polycystic ovarian syndrome caused by neonatal exposure to tributyltin and bisphenol A in rats.

The development of polycystic ovary syndrome (PCOS) could be caused by exposure to environmental endocrine disrupting chemicals (EDCs). In the current study, two commonly found EDCs, bisphenol A (BPA) and tributyltin (TBT), were investigated for their effects on PCOS occurrence in neonatal female rats. TBT (10 and 100 ng kg-1 d-1), BPA (50 μg kg-1 d-1), and a mixture of the two (TBT 100 ng kg-1 d-1 with BPA 50 μg kg-1 d-1) were administered to female rats from postnatal day 1-16. TBT, BPA, and TBT + BPA treatment resulted in an irregular estrus cycle and disturbed ovarian development, with less corpora lutea and antral follicles, but more atretic follicles and cysts. In addition, serum testosterone and luteinizing hormone levels were significantly elevated, whereas a reduced level of serum sex hormone-binding globulin was observed after TBT100, BPA50, and TBT + BPA treatments. Moreover, gene expression analyses identified significant differential expression of the genes involved in a variety of biological pathways, such as lipid transport and steroidogenesis. Moreover, the expression level of proteins regulating lipid and androgen biosynthesis was elevated after the treatments. In conclusion, this study demonstrated that exposure to TBT, BPA, and a mixture of the two in newborn rats could contribute to a PCOS-like syndrome. The mechanism of PCOS pathogenesis caused by exposure to TBT and BPA is likely to be mediated by the lipid metabolism and steroidogenesis pathways. Our results provide novel insight into female reproduction affected by EDCs, which may be helpful for revealing the pathogenesis of PCOS.