HUANG Shao′e, XIE Liqing, DING Zhizhu, ZHAO Xiaoyong, ZHANG Xiaoli
Chinese Journal of Reproductive Health. 2024, 35(6): 521-530.
Objective To investigate the regulation of the methyltransferase inhibitor 5-aza-2-deoxycytidine (5-AZA-DC) on trophoblast apoptosis, proliferation, invasion, and migration in preeclampsia. Methods Placental tissue samples were collected from 40 normal pregnancies (normal pregnancy group) and 40 preeclampsia (PE group) patients. Hematoxylin-eosin (HE) staining was performed on the placental tissues after delivery, and whole-genome bisulfite sequencing (WGBS) was conducted on the placental tissues. Trophoblast cell lines HTR8/Svneo, JEG-3, JAR, and BeWo were cultured in vitro and divided into blank control group (Control group), STAT3 silencing group (shSTAT3 group), and STAT3 overexpression group (STAT3OE group). Cells were treated with 5-AZA-DC, and cell apoptosis, proliferation, invasion, and migration were assessed using CCK8, flow cytometry, Transwell invasion assays, and scratch assays. Statistical analysis was performed using t-tests and one-way ANOVA. Results (1) In placental tissue, compared to the normal pregnancy group, the PE group showed reduced vascular lumens, vascular occlusion, blood flow, fibrin deposition in the intervillous stroma, and visible infarction and hyaline degeneration in the villi. WGBS revealed a significant increase in methylation levels in the PE group, with statistically significant differences in the methylation of genes such as STAT3 [(17.25±1.05 vs 30.36±1.33),P<0.01],PTEN[(13.33±0.71 vs 23.05±1.17),P<0.02],TSC2[(15.28±1.43 vs 26.53±1.15),P<0.02]. (2) In the cell lines, compared to the Control group, 5-AZA-DC intervention significantly reduced trophoblast apoptosis while increasing cell proliferation, invasion, and migration. These differences were statistically significant (P<0.05). Conclusion STAT3 is a key gene in the pathogenesis of preeclampsia.The intervention with 5-AZA-DC intervention has significant effects on trophoblast apoptosis, proliferation, invasion, and migration in preeclampsia. 5-AZA-DC may be a potential epigenetic therapeutic agent for preeclampsia.