Discussion
This study demonstrated that PINK1-mediated mitophagy might played a protective role in PE by reducing ROS and trophoblast pyroptosis.
Methods
The morphology of mitochondrial in placenta were observed by transmission electron microscopy. The localization of PINK1 in the placenta was determined by immunohistochemistry. The expression levels of PINK1, PARKIN, LC3B, and SQSTM1 and pyroptosis-related molecules were compared between normal pregnancies and PE. We used hypoxia/reoxygenation (H/R) to stimulate the trophoblast hypoxia environment. HTR-8/SVneo cells were transfected with PINK1 plasmid and si-PINK1, respectively, and then were treated with H/R, to determine whether PINK1 regulated ROS and HTR-8/Svneo pyroptosis. Finally, ROS production was inhibited by MitoTEMPO to observe whether the pro-pyroptosis effect of PINK1 knockdown is alleviated.
Results
Swollen mitochondrial were accumulated in the PE placentae. PINK1 is localized on villus trophoblast (VTs) and extravillous trophoblast (EVTs). PINK1-mediated mitophagy was abolished in the PE placenta, while the levels of pyroptosis were induced. H/R stimulation aggravated the downregulation of mitophagy and the up-regulation of pyroptosis. Overexpression of PINK1 mitigated H/R-induced upregulation of ROS and pyroptosis while silencing PINK1 did the opposite. Reducing ROS production can effectively resist the pro-pyroptosis effect of PINK1 knockdown.