SAT423 Regulation Of The Male Neuroendocrine Axis By Per- And Polyfluoroalkyl Substances (PFASs)

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Abstract Disclosure: S. Bradley: None. J. Hayworth: None. B.T. Akingbemi: None. Introduction and Objectives. Per- and polyfluoroalkyl substances (PFASs) are man-made chemicals present in several consumer products. Unregulated disposal of PFASs into landfills contaminates groundwater sources for both drinking and agriculture and raise public health concerns. Short-chain or emerging PFASs, such as perfluorobutanoic acid (PFBA) and perfluorobutanesulfonic acid (PFBS), are thought to be safer than perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) due to decreased toxicity and rapid environmental degradation. The present study is designed to compare the endocrine-disrupting properties of legacy and emerging PFASs. Methods. Male Long-Evans rats (n=12) were fed test chemicals (PFOA, PFOS, PFBA, PFBS) in drinking water at 1, 10, 100, and 1000 ng/L from 21 to 35 days of age (acute or 14-day exposure) or at 10 or 100 ng/L from postnatal days 21 to 49 (chronic or 28-day exposure). At termination of chemical exposures, animals were sacrificed to obtain testicular tissue and Leydig cell fractions for incubation in DMEM/F-12 culture medium for 3 h for basal T or with 100 ng/mL ovine LH (NIDDK, NIH) to measure LH-stimulated testosterone (T) production by RIA. Testes, Leydig cells and pituitary glands were processed for western blot analyses of protein gene expression. Results. Acute exposures of male rats to PFBA at 10 ng/L increased basal (p<0.05) and LH-stimulated (p<0.00001) testicular T production just as basal testicular T production was increased by PFBS at 1 ng/L (p<0.05) and PFOS at 1000 ng/L (p<0.001). However, PFOS at 10 ng/L caused a decrease (p<0.001) in LH-stimulated testicular T production compared to control. Chronic exposures to PFOS and PFBS at 10 and 100 ng/L decreased (p< 0.001) basal testicular T production, but PFBA at 10 ng/L increased (p<0.05) LH-stimulated testicular T production. Testicular expression of the Mϋllerian Inhibiting Substance (MIS) protein was increased by PFOS and PFBA at 100 ng/L (p<0.05), whereas testicular inhibin-β protein was decreased (p<0.001) by all test chemicals at 10 and 100 ng/L doses except at the lower PFBA dose. Exposure to PFOA at 10 ng/L and PFBS at 100 ng/L increased (p<0.05) pituitary luteotropin subunit protein expression similar to PFBA at 100 ng/L and PFBS at 10 ng/L which increased (p<0.001) pituitary FSH-β protein. In Leydig cells, PFOA at 100 ng/L increased (p<0.0001) but PFBA at 100 ng/L decreased (p<0.05) the StAR protein. Cytochrome P450 17A1 enzyme protein was decreased by both PFBA and PFOS at 100 ng/L (p<0.05) in Leydig cells compared to control. Conclusions. These observations showed that both legacy and emerging PFASs can impact the male neuroendocrine-reproductive axis. PFASs increased as well as decreased gonadal T secretion with implications for germ cell development, sperm production and male fertility. Presentation: Saturday, June 17, 2023