During normal pregnancy, the placental trophoblast secretes a variety of
steroid hormones and participates in the regulation of maternal physiological functions and fetal development. The
CYP11A1 gene encodes the
cholesterol side-chain cleavage enzyme P450scc, which catalyzes the production of
pregnenolone from
cholesterol, which is the first step in the synthesis of all
steroid hormones. Under the influence of
genetic susceptibility and certain environmental factors, such as drugs and toxins, the expression of
CYP11A1 can be upregulated, thereby affecting
steroid metabolism and physiological functions in trophoblast cells, as well as fetal development. Here, we demonstrate that upregulation of
CYP11A1 in the BeWo cell line triggers excessive mitochondrial oxidative stress, leads to mitochondrial damage and
interleukin-6 release, and contributes to the inhibition of proliferation and DNA damage in neuronal stem cells (NSCs). Furthermore, oxidative stress and
inflammation can be ameliorated by
vitamin D3 in a dose-dependent manner, thereby facilitating the rescue of NSC impairment. Our findings reveal the underlying mechanism in which upregulation of
CYP11A1 is detrimental to the physiological function of trophoblasts and demonstrate the beneficial effects of
vitamin D supplementation in preventing placental and neurodevelopmental damage associated with
CYP11A1 upregulation during pregnancy.