3-MCPD exposure enhances ovarian fibrosis and reduces oocyte quality in mice

Abstract

3-monochloro-1,2-propanediol (3-MCPD) is a food contaminant believed to be harmful to human health. Previous studies showed that 3-MCPD exerts toxic effects in multiple tissues, but whether 3-MCPD affects female reproductive function remained unknown. Here, using mouse gastric lavage models, we report that 3-MCPD exposure for four weeks affected body growth, decreased the ovary/body weight ratio, and increased atretic follicle numbers. Expression levels of follicular development-related factors decreased. Further studies found that ovaries from 3-MCPD exposed mice had activated the Transforming Growth Factor-β (TGF-β) signaling pathway and promoted ovarian fibrosis. Increased TNF-α, IL-1 and NF-κB expression also indicated the occurrence of ovarian inflammation. Exposure to 3-MCPD stimulated the caspase pathway and enhanced granulosa cell apoptosis. Consistent with disrupted ovarian homeostasis, 3-MCPD exposure interfered with mitochondrial function, generated more reactive oxygen species, increased ferrous ion and lipid peroxidation levels, and resulted in decreased oocyte development potential. Collectively, these findings indicated that 3-MCPD exposure induced ovarian inflammation and fibrosis, and caused disorders of mitochondrial function and ferrous ion homeostasis in oocytes, which consequently disturbed follicle maturation and reduced oocyte quality.