No abstract

Preeclampsia (PE) is a major cause of maternal death worldwide, characterized by newly onset of hypertension (>140/90 mmHg) and proteinuria (>300 mg in a 24-h urine) after 20 weeks of gestation. 1,2 Successful placental and foetal development during the progression of pregnancy require adequate invasion of extravillous trophoblast cells into the uterine, and impaired trophoblastic invasion

The process of placental invasion is essential for a successful pregnancy. Leptin is involved in trophoblast invasiveness, and its dysregulation is connected with a series of diseases, including preeclampsia. However, the knowledge of the precise mechanisms in leptin-induced trophoblast invasiveness is still limited. According to the present research, transwell assay suggested that leptin is a dose- and time-dependent regulator in inducing HTR-8/SVneo cell invasion. Western blot analysis and immunofluorescence staining revealed that leptin-induced MMP9 expression is essential in the invasion process of HTR-8/SVneo cells. Mechanistically, we demonstrated that leptin activated β-catenin via the crosstalk between the MTA1/WNT and PI3K/AKT pathways. Besides, we showed that downregulating the key molecules in the signaling pathways by siRNA can inhibit leptin-induced MMP9 expression and further suppress invasion of HTR-8/SVneo cells. In conclusion, our study revealed a new regulatory mechanism of leptin-induced HTR-8/SVneo cell invasiveness and will provide novel insights into the causes and potential therapeutic targets for diseases related to dysregulation of trophoblast invasion in the future.

The components of the in vivo microenvironment are BMSCs and miRNAs that have a critical role in the development of pregnancy. Our aim was to further investigate the effect of the miRNAs of BMSC origin on pregnancy injury. Exosomal miR-378a-3p secreted by BMSCs was identified by electron microscopy and miR-378a-3p expression was measured during gestational injury. Target scan detects the correlation of XIAP and miR-378a-3p which was confirmed by luciferase activity along with analysis of cell growth by MTT assay and cell invasion by Transwell and EMT expression. Exosomal miR-378a-3p derived from BMSCs promoted proliferation and migration and invasion of trophoblast. miR-378a-3p targeted XIAP and its overexpression could significantly increase EMT switching. The miR-378a-3p/XIAP axis is critical in trophoblastic cell migration and EMT and is involved in pregnancy injury progression, indicating that it might be a novel potential target for the treatment of pregnancy injury.