Quantitative proteomic analysis of mouse testis uncovers cellular pathways associated with bisphenol A (BPA)-induced male infertility.

Quantitative proteomic analysis was performed using iTRAQ to explore the potential regulation of differentially expressed proteins (DEPs) by bisphenol A (BPA) in murine testis. BPA was intraperitoneally injected into mice at a dose of 100 mg/kg body weight for 7 consecutive days. After BPA treatment, the histopathology changes of testis were examined. The circulating levels of testosterone (T) and estradiol (E2) were determined. iTRAQ was used to assess the expression levels of DEPs and to reveal potential interactions between different DEPs. Results showed that BPA caused histological damage in testicular tissues. The levels of T and E2 were affected by BPA exposure. The abundances of orosomucoid 1 (Orm1), haptoglobin (Hp), and insulin-like 3 (Insl3) were significantly lower in BPA-treated mice than those in control mice. The expression changes in the above-mentioned proteins were further validated at the protein level using Western blot analysis. We concluded that BPA affects histological morphology of testis and sex hormone productions. The regulation of key proteins (such as Orm1, Hp and Insl3) may reflect that these proteins may serve as important factors in male reproductive disorders caused by BPA, and these proteins are probably biomarkers for infertility caused by endocrine disrupting chemicals.