Beauvericin disrupts G2/M transition and induces meiotic arrest during mouse oocyte maturation.

Beauvericin (BEA) is a mycotoxin produced by fungi of the genus Fusarium that causes adverse toxic effects in humans and livestock. Previous studies have demonstrated that BEA causes reproductive toxicity in pigs and juvenile sheep. However, the effects of BEA on meiotic resumption and the underlying mechanisms remain unclear. In this study, we investigated the molecular mechanisms underlying meiotic failure caused by the toxic effects of BEA on fully grown immature mouse oocytes. Exposure to BEA led to DNA damage, affected phosphatidylinositol 3-kinase/protein kinase B/phosphodiesterase 3 A (PI3K/AKT/PDE3A)-mediated cAMP signaling, and inhibited cyclin-dependent kinase (CDK) complex (MPF) activation by modulating CDK1 activity through altered expression of Wee1 and CDC25B. These disruptions ultimately led to germinal vesicle arrest during in vitro oocyte maturation. Our findings suggest that BEA treatment blocks germinal vesicle breakdown by affecting the PI3K/AKT/PDE3A-mediated cAMP-MPF pathway, resulting in the failure of meiotic progression and defects in the maturation of mammalian oocytes.