Parkin aggravates symptoms of preeclampsia through promoting mitophagy and apoptosis.

Abstract

Background: Preeclampsia is a serious pregnancy complication with significant maternal and fetal morbidity. Mitophagy plays a crucial role in its pathogenesis. The importance of this study lies in evaluating the role of parkin in preeclampsia, which may offer new insights into the management of this disease.

Objectives: This study was designed to evaluate the role of parkin in preeclampsia.

Material and methods: To induce a preeclampsia model, pregnant female rats were administered N-nitro-L-arginine methyl ester (L-NAME) subcutaneously at a dose of 50 mg/(kg·day) starting on gestational day 14 for 7 consecutive days. Uteroplacental tissues were then collected, and chorionic trophoblast cells were isolated. Systolic blood pressure (SBP) and urine protein content were measured on days 12 and 20 of pregnancy. Hematoxylin-eosin (H&E) staining and TUNEL staining were employed to assess pathological changes and apoptosis in uteroplacental tissues, respectively. Reverse transcription polymerase chain reaction (RT-qPCR) and western blot analysis were performed to evaluate mRNA and protein expression levels associated with cellular function, mitophagy and the PINK1/parkin signaling pathway.

Results: Compared to the negavtive control (NC) group, rats in the model group showed elevated SBP and urine protein levels (p < 0.01). Chorionic trophoblast cells exhibited substantial damage, with significantly increased levels of apoptosis and autophagy. Moreover, parkin mRNA and protein expression levels were markedly upregulated in the model group. Overexpression of parkin in chorionic trophoblast cells enhanced apoptosis and mitophagy, while the autophagy inhibitor 3-methyladenine (3-MA) significantly alleviated the damage caused by overexpression of parkin.

Conclusions: Parkin aggravates the symptoms of preeclampsia by increasing mitophagy and apoptosis.