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bioRxiv · 10.1101/2023.01.18.524658

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

Varma, S.·Molangiri, A.·Kona, S. R.·Ibrahim, A.·Duttaroy, A. K.·Basak, S.
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Abstract

Daily exposure to bisphenols can affect reproductive functions due to their pseudo-estrogenic and/or anti-androgenic effects. Testicular lipids contain high levels of polyunsaturated fatty acids necessary for sperm maturity, motility, and spermatogenesis. Whether prenatal exposure to bisphenols alters testicular fatty acid metabolism in adult offspring is unknown. Pregnant Wistar rats were gavaged from gestational day 4 to 21 with BPA and BPS (0.0, 0.4, 4.0, 40.0 g/kg bw/d). Despite increased body and testis weight, the total testicular cholesterol, triglyceride, and plasma fatty acids were unaffected in offspring. Lipogenesis was upregulated 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 decreased in the BPA-exposed testis, while BPS exposure had no effects. The expression of PPAR, PPAR{gamma} proteins and CATSPER2 mRNA were decreased, which are important for energy dissipation and motility of the sperm in the testis. The endogenous conversion of linoleic acid,18:2n-6 (LA), to ARA was impaired by a reduced ARA/LA ratio and decreased FADS1 expression in BPA-exposed testis. Collectively, fetal BPA exposure affected endogenous long-chain fatty acid metabolism and steroidogenesis in the adult testis, which might dysregulate sperm maturation and quality. HighlightsO_LIIn utero BPA exposure not BPS affected testicular long-chain n-6 PUFA metabolism in offspring C_LIO_LIFetal exposure to BPA alters delta-9-desaturase indices in the adult testis C_LIO_LIBPA exposure reduced fatty acid desaturase1 expression in offspring testis C_LIO_LIFetal BPA exposure dysregulated lipogenesis in offspring testis C_LI

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Varma, S., Molangiri, A., Kona, S. R., Ibrahim, A., Duttaroy, A. K., Basak, S.. 2023-01-20. Fetal exposure to endocrine disrupting-bisphenol A (BPA) alters testicular fatty acid metabolism in the adult offspring: relevance to sperm maturation and quality. https://doi.org/10.1101/2023.01.18.524658

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