Effect of 4-nitrophenol on the reproductive capacity of female mice

Diesel exhaust particle-derived 4-nitrophenol (PNP) has been demonstrated to exhibit anti-androgenic and estrogenic effects, as well as the potential to disrupt the hypothalamic-pituitary-gonadal axis in male rats. Studies have also confirmed PNP's toxicity in various tissues; however, its harmful effects on the female reproductive system remain unclear. Therefore, this study investigated PNP's reproductive toxicity in female mice. While PNP exposure did not significantly affect body weight, it disrupted follicular development by altering ovarian homeostasis. A high level of apoptosis was observed in ovarian follicles, consequently impairing oocyte development. Molecular analyses revealed that PNP induced oxidative stress, premature apoptosis, and mitochondrial dysfunction. These effects were evidenced by increased reactive oxygen species production, abnormal mitochondrial distribution and structure, and membrane potential depolarization. Furthermore, PNP-exposed female mice exhibited reduced fertilization rates, impaired blastocyst formation, and fewer offspring following in vitro fertilization. Collectively, these findings suggest that PNP destabilizes the ovarian microenvironment, thereby compromising oocyte developmental potential and reducing offspring number.