Carbendazim detection in human follicular fluid: Impact on human granulosa cell function (KGNs and primary cells) and mouse ovarian physiology

This study investigates the endocrine-disrupting effects of the fungicide carbendazim (CBZ) on human and murine reproductive health. Mass spectrometry confirmed systemic human exposure, detecting CBZ in the plasma and follicular fluid of 15-18% of the women sampled. In vitro, CBZ did not affect viability in human KGN and primary granulosa cells (hGCs) but significantly inhibited KGN proliferation. Furthermore, CBZ reduced steroidogenesis stimulated by FSH, LH, or IGF-1 in both cell types. This dysfunction correlated with a dose-dependent increase in the Oxidative Stress Index, driven by elevated total oxidant status and reactive oxygen species. Corroborating these findings, in vivo murine models exposed to CBZ (100 μg/kg/day) exhibited a prolonged diestrus phase, alongside reduced numbers of corpora lutea and preovulatory follicles, and decreased gonadotropin and E2 plasma levels. Collectively, these results identify CBZ as a potent reproductive toxicant that impairs ovarian function via oxidative stress-mediated hormonal disruption.