Maternal Cypermethrin Exposure during the Perinatal Period Impairs Testicular Development in C57BL Male Offspring

Numerous studies have demonstrated that endocrine-disrupting compounds (EDC) are a possible cause of male reproductive organ malfunction and malformation. Cypermethrin (CYP) is a widely used synthetic pyrethroid and a potential EDC. This study aimed to examine the effects of perinatal exposure to low-dose CYP on the development and function of the offspring testes. Pregnant mice were intragastrically administered 0.12 to 12 mg/kg/day CYP from embryonic day 0.5 (E0.5) to weaning (PD21.5, postnatal day 21.5). Maternal exposure to 0.12, 1.2, and 12 mg/kg/day CYP affected the body and organ weight of the offspring. Exposure of CYP led to a dose-dependent decrease in the male-to-female sex ratio. A histopathological analysis revealed a thinner seminiferous epithelium layer at PD21.5, interstitial hyperplasia at PD45.5, and germ cell vacuolization at PD90.5 in the 12 mg/kg/day CYP group. The TUNEL assay results revealed increased germ cell apoptosis in the 12 mg/kg/day CYP group. The serum testosterone (T) level decreased, whereas the estradiol level increased with age in the 1.2 and 12 mg/kg/day CYP groups. The RT-PCR analysis demonstrated decreased expression of T production-related, mitosis-related, and meiosis-related genes in the 1.2 and 12 mg/kg/day CYP groups. The in vitro experimental results demonstrated reduced expression of steroidogenesis genes and decreased T levels. It is concluded that perinatal exposure to low-dose CYP affects testes development and function in adults.