Inhibition of Nicotinamide adenine dinucleotide phosphate oxidase 4 attenuates cell apoptosis and oxidative stress in a rat model of polycystic ovary syndrome through the activation of Nrf-2/HO-1 signaling pathway

Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder in reproductive-aged women. In this study, a rat model of PCOS was established by subcutaneous injection of dehydroepiandrosterone (DHEA). NOX4 was highly expressed in PCOS rat ovaries, while its specific role in PCOS remains unclear. Lentivirusmediated shRNA targeting NOX4 inhibited oxidative stress by reducing ROS, 4-HNE and MDA levels, and increasing SOD and GPX activities in rat ovaries. NOX4 deficiency increased Bcl-2 levels and decreased Bax, cleaved caspase-3 and cleaved caspase-9 levels and DHEA-induced cell apoptosis in rat ovaries. Similar to the in vivo results, NOX4 silencing inhibited oxidative stress and cell apoptosis in DHEA-treated rat granulosa cells. Moreover, NOX4 silencing promoted Nrf-2 translocation, and the expression of Nrf-2 and HO-1 both in vivo and in vitro. Thus, NOX4 deficiency may ameliorate PCOS in rats by reducing oxidative stress and cell apoptosis via activating the Nrf-2/HO-1 signal pathway.