Reproductive toxicity of per- and polyfluoroalkyl substances

Per- and polyfluoroalkyl substances (PFAS) are synthetic fluorinated compounds known for their persistence in the environment and widespread presence in consumer products. Human exposure occurs through multiple routes, leading to bioaccumulation in various tissues and significant health concerns, particularly reproductive toxicity. This review critically examines the reproductive effects of both long- and short-chain PFAS and explores the mechanisms underlying their toxicity. PFAS have been shown to downregulate key genes involved in steroidogenesis, including steroidogenic acute regulatory protein (StAR), cytochrome P450 enzymes (CYP11A1, CYP17A1), 3β-hydroxysteroid dehydrogenase, and 17β-hydroxysteroid dehydrogenase. Additionally, PFAS exert direct toxic effects on developing spermatogonia and oocytes, impairing reproductive function. While most research has focused on long-chain PFAS, this review highlights that short-chain PFAS pose comparable risks, necessitating further investigation. The ability to biodegrade PFAS has been demonstrated, offering a potential approach to mitigate tissue accumulation and reduce associated health risks. However, gaps remain in our understanding of PFAS mechanisms, with conflicting evidence across different compounds and study models. Standardized methodologies and long-term human studies are essential to fully elucidate the chronic effects of PFAS exposure and develop effective mitigation strategies.