Potential risk of premature ovarian insufficiency from atrazine exposure: insights into molecular pathways and regulatory implications.

Atrazine (ATZ), also known as 6-chloro-4-N-ethyl-2-N-propan-2-yl-1,3,5-triazine-2,4-diamine, is a common chlorinated triazine herbicide that has caused serious health and environmental concerns due to its persistence and classification as an endocrine-disrupting chemical. Atrazine (ATZ), a widely detected contaminant in drinking water, surface water, soil, and groundwater, has been associated with hormonal imbalances-particularly disrupting the luteinizing hormone (LH) and follicle-stimulating hormone (FSH) axis, which is essential for ovarian function and follicular development. Emerging findings suggest that ATZ may contribute to ovarian dysfunction and potentially accelerate processes associated with premature ovarian insufficiency (POI), characterized by oocyte depletion, diminished ovarian reserve, and hormonal imbalance leading to early infertility. Mechanistically, ATZ disrupts several cellular signaling pathways, including MAPK, TGF-β/Smad, and Nrf2/Keap1, contributing to oxidative stress, apoptosis, granulosa cell dysfunction, and DNA damage. These molecular alterations culminate in impaired folliculogenesis and hormonal instability. Regulatory agencies worldwide, including the WHO, European Union, US EPA, and authorities in Brazil, India, and Argentina, are continually revising atrazine exposure limits in response to increasing evidence of its endocrine-disrupting potential and ecological hazards. This review highlights the known and plausible mechanisms by which ATZ disrupts ovarian function and follicular dynamics, which could be among the contributing factors potentially leading to POI. In light of emerging evidence and global regulatory disparities, it underscores the urgent need for stricter environmental policies, comprehensive toxicological assessments, and mechanistic studies to better evaluate ATZ's reproductive risks and inform future regulations.