Silica nanoparticle exposure inducing granulosa cell apoptosis and follicular atresia in female Balb/c mice.

Given that the effects of ultrafine fractions (< 0.1 μm) on reproductive diseases are gaining attention, this study aimed to explore the influence of silica nanoparticle (SiNP)-induced female reproductive dysfunction. In this study, 80 female mice were randomly divided into four groups including a control group and three concentrations of SiNP groups (7, 21, 35 mg/kg). Mice were exposed to the vehicle control and silica nanoparticles by tracheal perfusion every 3 days a total of five times in 15 days. Then, half of the mice in each group were sacrificed on 15 and 30 days after the first dose, respectively. Our findings indicated that SiNPs can result in ovarian damage, cause an imbalance of sex hormones, increase the number of atretic and primary follicles, and induce oxidative stress and DNA strand breaks in ovary by day 15. The protein expressions of ATM, CHK-2, P53, E2F1, P73, BAX, Caspase-9, and Caspase-3 were significantly increased, while expressions of RAD51 were down-regulated after SiNP exposure by days 15. Estradiol increased, while progesterone increased in low dose and decreased in high dose after SiNP exposure by 15 days. However, these changes were recovered by 30 days. The results suggest that SiNPs can cause reversible damage to follicles in mice. SiNPs could primarily cause DNA damage and DNA damage response through oxidative stress, while DNA damage repair failure because of severe DNA damage activated the mitochondrial apoptosis pathway and therefore resulted in apoptosis of granulosa cell. In addition, the disorder of reproductive endocrine function caused by SiNPs could be another reason for SiNP-induced reproductive dysfunction in mice. These events in turn induce the follicles to undergo atresia.