NRF2 protects against ROS-induced preterm premature rupture of membranes through regulation of mitochondria †

Biol Reprod. 2023 Jul 10:ioad075. doi: 10.1093/biolre/ioad075. Online ahead of print.ABSTRACTPreterm premature rupture of membranes (pPROM) is a major cause of preterm birth and neonatal mortality. Reactive oxygen species (ROS) have been identified as a critical factor in the development of pPROM. Mitochondria are known to be the primary source of ROS and play a vital role in maintaining cellular function. The Nuclear erythroid 2-related factor 2 (NRF2) has been demonstrated to play a crucial role in regulating mitochondrial function. However, research exploring the impact of NRF2-regulated mitochondria on pPROM is limited. Therefore, we collected fetal membrane tissues from pPROM and spontaneous preterm labor (sPTL) puerpera, measured the expression level of NRF2, and evaluated the degree of mitochondrial damage in both groups. Additionally, we isolated human amniotic epithelial cells (hAECs) from the fetal membranes and employed siRNA to suppress NRF2 expression, enabling us to evaluate the impact of NRF2 on mitochondrial damage and ROS production. Our findings indicated that the expression level of NRF2 in pPROM fetal membranes was significantly lower than in sPTL fetal membranes, accompanied by increased mitochondrial damage. Furthermore, following the inhibition of NRF2 in hAECs, the degree of mitochondrial damage was significantly exacerbated, along with a marked increase in both cellular and mitochondrial ROS levels. The regulation of the mitochondrial metabolic proces...
Source: Biology of Reproduction - Category: Reproduction Medicine Authors: Source Type: research