Microplastics exposure causes premature ovarian aging via inducing mitochondrial dysfunction

Ovarian aging represents a significant risk factor for female infertility, primarily due to a decline in ovarian reserve and diminished oocyte quality. However, whether microplastics (MPs) exposure poses a potential factor in inducing ovarian aging and the underlying mechanisms remain poorly understood. In this study, we demonstrated that MPs exposure accelerates ovarian aging, characterized by elevated expression of senescence markers (p16 and p21) and increased fibrosis. Mechanistic analysis indicated that MPs exposure led to ovarian inflammatory damage and mitochondrial dysfunction, which contribute to reduced ovarian reserve. Furthermore, MPs exposure compromised oocyte maturation competence and embryo development by triggering mitochondrial dysfunction and DNA damage. Multi-omics analysis identified L-arginine as a crucial metabolite that protects oocytes from MPs-induced aging. Notably, L-arginine supplementation significantly mitigated the aging phenotypes induced by MPs, as evidenced by reduced ovarian fibrosis, inflammatory damage, and mitochondrial dysfunction, alongside enhanced oocyte quality. These findings provide theoretical support for reproductive protection against MPs and inform environmental risk assessments.