Exposure to Long- and Short-Chain Per- and Polyfluoroalkyl Substances in Mice and Ovarian-Related Outcomes: An in Vivo and in Vitro Study

BACKGROUND: The extensive use of per- and polyfluoroalkyl substances (PFAS) has led to environmental contamination and bioaccumulation of these substances. Previous research linked PFAS exposure to female reproductive disorders, but the mechanism remains elusive. Further, most studies focused on legacy long-chain PFOA and PFOS, yet the reproductive impacts of other long-chain PFAS and short-chain alternatives are rarely explored. OBJECTIVES: We investigated the effects of long- and short-chain PFAS on the mouse ovary and further evaluated the toxic mechanisms of long-chain perfluorononanoic acid (PFNA). METHODS: mouse exposure model to verify the accumulation of PFNA in the ovary and its ovarian-disrupting effects. RESULTS: extrapolation analyses estimated follicular rupture as the most sensitive end point and that observed effects occurred in the range of human exposure to long-chain PFAS. DISCUSSION: agonist in granulosa cells to interfere with gonadotropin-dependent follicle growth, hormone secretion, and ovulation; and exposure to high levels of PFAS may cause adverse ovarian outcomes. https://doi.org/10.1289/EHP14876.