Pyraclostrobin-induced mitochondrial dysfunction disrupts female reproductive function in vitro and in vivo.

Pyraclostrobin is a widely used strobilurin fungicide that is frequently detected in agricultural environments and food, raising concerns about human exposure. However, the toxicological mechanisms affecting female reproductive health and pregnancy are not fully understood. This study assessed the female reproductive toxicity of pyraclostrobin using human trophoblastic cells (HTR-8/SVneo), endometrial stromal cells (T-HESCs), and an in vivo mouse model (C57BL/6 J). In vitro, pyraclostrobin induced concentration-dependent cytotoxicity accompanied by mitochondrial dysfunction, apoptosis, cell cycle arrest, oxidative stress, and calcium ion homeostasis disruption. Alongside the cellular effects of pyraclostrobin treatment, a decreased migration ability of trophoblastic cells and disturbances in hormone receptor expression levels were observed. The mouse model was divided into three groups, which received either the vehicle or pyraclostrobin at doses of 2 or 4 mg/kg bw/day. The treatments were administered orally at 4 weeks of age until gestational day 15.5. The mice were allowed to mate with normal adult male mice at 8 weeks of age. Pyraclostrobin exposure resulted in adverse reproductive outcomes, such as pregnancy failure, fetal growth restriction, dysregulated expression of placenta and ovarian function-associated genes, and decreased ovarian reserve. Collectively, these findings provide mechanistically relevant cellular responses consistent with mitochondrial dysfunction and support potential reproductive risks. This study integrates implantation-related human cell models with in vivo pregnancy phenotyping. It also emphasizes the potential health risks associated with environmental exposure to pyraclostrobin.