The reproductive and transgenerational toxicity of microplastics and nanoplastics: A threat to mammalian fertility in both sexes.

Microplastics (MPs) and nanoplastics (NPs) are extensively distributed in the environment. However, a comprehensive review and in-depth discussion on the effects of MPs and NPs to reproductive capacity and transgenerational toxicity on mammals, especially on humans, is lacked. It is suggested that microplastics and nanoplastics could accumulate in mammalian reproductive organs and exert toxic effects on the reproductive system for both sexes. For males, the damage of microplastics consists of abnormal testicular and sperm structure, decreased sperm vitality, and endocrine disruption, which were caused by oxidative stress, inflammation, apoptosis of testicular cells, autophagy, abnormal cytoskeleton, and abnormal hypothalamic-pituitary-testicular axis. For females, the damage of microplastics includes abnormal ovary and uterus structure and endocrine disruption, which were caused by oxidative stress, inflammation, granulosa cell apoptosis, hypothalamic-pituitary-ovary axis abnormalities, and tissue fibrosis. For transgenerational toxicity, premature mortality existed in the rodent offspring after maternal exposure to microplastics. Among the surviving offspring, metabolic disorders, reproductive dysfunction, immune, neurodevelopmental, and cognitive disorders were detected, and these events directly correlated with transgenerational translocation of MPs and NPs. Studies on human-derived cells or organoids demonstrated that transgenerational toxicity studies for both sexes are yet in the phase of exploring suitable experimental models, and more detailed research on the threat of MPs and NPs to human fertility is still urgently needed. Further studies will help assess the MPs and NPs threat to public fertility and reproductive health risks.