Fetal exposure to endocrine disrupting-bisphenol A (BPA) alters testicular fatty acid metabolism in the adult offspring: relevance to sperm maturation and quality

Abstract

Daily exposure to endocrine-disrupting substances like bisphenols can affect reproductive functions due to their pseudo-estrogenic and/or anti-androgenic effects. Testicular lipids contain high levels of polyunsaturated fatty acids (PUFA) necessary for sperm maturity, motility, and spermatogenesis. Whether prenatal exposure to bisphenols alters testicular fatty acid metabolism in the offspring is unknown. The effects of in-utero bisphenol exposure on the lipid metabolism of adult offspring testis (90d) were examined. Pregnant Wistar rats were exposed to BPA and BPS (0.0, 0.4, 4.0, 40.0 μg/kg bw/d) by oral gavage from gestational day 4 to 21. Despite increased body and testis weight, the fetal BPA exposure did not affect total testicular cholesterol, triglyceride levels, and plasma fatty acid composition in offspring. Lipogenesis was upregulated as evidenced by increased SCD-1, SCD-2, and expression of lipid storage (ADRP) and trafficking protein (FABP4). The arachidonic acid, 20:4 n-6 (ARA) and docosapentaenoic acid, 22:5 n-6 (DPA) levels were significantly decreased (p<0.05) in the BPA-exposed testis, while BPS exposure had no effects. The expression of PPAR-signaling proteins (PPARα and PPARγ) was reduced in the testis, which is important for sperm energy dissipation. BPA exposure reduced the expression of CATSPER2 in adult offspring testis. The endogenous conversion of linoleic acid,18:2n-6 (LA), to ARA was impaired, as evidenced by a reduced ARA/LA ratio and decreased FADS1 expression. The reduced ARA might have impacted steroidogenesis. Scattered and decreased signals of FADS1 suggest its disrupted activities and reduced expression in these testes. The BPA exposure on the testis and its impacts on endogenous lipid metabolism might be underlying factors that dysregulate sperm maturation and quality.