Glycine alleviates ovarian granulosa cell ferroptosis induced by ERα-mediated internalization of polystyrene microplastics

Polystyrene microplastics (PSs), pervasive environmental contaminants found in food and human tissues, pose an emerging threat to reproductive health. Elucidating the mechanisms underlying PS-induced toxicity and identifying effective interventions to mitigate adverse effects are therefore critically important. Here, our findings demonstrated that PS exposure in 5-week-old female SPF Kunming mice leads to decreased serum hormone levels and reduced transzonal projections. Furthermore, this study revealed that PS-induced ferroptosis in ovarian granulosa cells. Mechanistically, ERα-mediated PS internalization led to activation of the YAP1-ACSL4 signalling and subsequent lipid peroxidation. Moreover, we demonstrated that glycine effectively alleviate PS-induced ferroptosis by modulating lysosome-dependent ferritin degradation in a PAT1-dependent manner, thereby restoring iron homeostasis. Taken together, these findings revealed that PS exposure triggers ACSL4 overexpression and iron overload in ovarian granulosa cells, whereas glycine restored iron homeostasis via lysosome-mediated ferritinophagy. This study provides critical insights into the reproductive health risks of PS exposure and offers a potential intervention strategy.