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Preeclampsia (PE) is a disease specific to pregnancy that causes 9–10 % of maternal deaths. Early-onset PE (<34 weeks' gestation) is the most dangerous category of PE. Wnt7a and GPR124 (G protein-coupled receptor 124) are widely expressed in the human reproductive process. Especially during embryogenesis and tumorigenesis, Wnt7a plays a crucial role. However, few studies have examined the association between Wnt7a-GPR124 and early-onset PE. The aim of this study was to examine the significance of Wnt7a and GPR124 in early-onset PE as well as Wnt7a's role in trophoblast cells. Immunohistochemistry (IHC), real-time PCR, and western blotting (WB) were used to investigate Wnt7a and GPR124 expression in normal and early-onset PE placentas. Additionally, FACS, Transwell, and CCK-8 assays were used to diagnose Wnt7a involvement in migration, invasion, and proliferation. In the early-onset PE group, Wnt7a and GPR124 expression was significantly lower than in the normal group, especially in the area of syncytiotrophoblasts (STBs) and extravillous trophoblasts (EVTs). A negative correlation was found between Wnt7a RNA and GPR124 expression (r=−0.42, p<0.01). However, the Wnt7a RNA expression level was positive correlated with PE severity. In further cellular functional experiments, knockdown of Wnt7a inhibits HTR8/SVeno cells invasion and migration but has little effect on proliferation and apoptosis. Through the Wnt pathway, Wnt7a regulates trophoblast cell invasion and migration, and may contribute to early-onset preeclampsia pathogenesis. A molecular level study of Wnt7a will be needed to find downstream proteins and mechanisms of interaction. [ABSTRACT FROM AUTHOR]

Aim: Progesterone resistance is an epigenetic factor that reduces endometrial receptivity and causes implantation failure in women with endometriosis. In addition, dysregulated miRNAs contribute to the underlying pathogenic mechanisms of endometriosis. This study aimed to determine the effect of miR‐297 on the progesterone receptor (PR) expression and on insufficient decidualization of endometrial stromal cells (ESCs) within the eutopic endometria of infertile women with minimal or mild endometriosis. Methods: ESCs were isolated from infertile endometriosis and normal patients and were transfected with miR‐297 mimic or miR‐297 inhibitor or respective control. qRT‐PCR and western blot were conducted to quantify the expression of miR‐297 and PR. The effect of miR‐297 on ESCs decidualization was investigated by induced decidualization in vitro. Results: We observed an increase in miR‐297 expression and a decrease in the expression of PR in the ESCs from endometriosis patients. Moreover, the expression of PR, most notably PRB, was found to be downregulated following transfection with miR‐297 mimic and upregulated following treatment with miR‐297 inhibitor. In addition, overexpressed miR‐297 inhibited the decidualization of ESCs in vitro. We further determined that miR‐297 exerts direct regulatory effects on PR expression. Conclusions: We demonstrated that miR‐297 interferes with fertility by repressing the expression of PR and preventing efficient decidualization in eutopic endometria. Further, miR‐297 directly contributes to progesterone resistance in minimal or mild cases of endometriosis. Thus, regulation of miR‐297 may prove to be a promising therapeutic strategy for endometriosis. [ABSTRACT FROM AUTHOR]

Background. To investigate the effect of hypoxia on pulmonary artery endothelial cells and the role of NOTCH3 in endothelial-mesenchymal transition (EnMT) and to provide a research model for pulmonary disease and explain the pathogenesis of the pulmonary disease. Methods. Pulmonary artery endothelial cells were divided into two groups and cultured in normoxic and hypoxic environments, respectively. QPCR, western blot, and immunofluorescence were used to detect endothelial cell-specific marker protein and mRNA expression in each group, and the ability of endothelial cells migration was evaluated by scratch and transwell experiment. Results. The pulmonary artery endothelial cells in the normoxic group presented a typical pebble-like arrangement, and the endothelial cells in hypoxic culture showed a long spindle appearance. Hypoxia induced high expression of NOTCH3, Jagged-1, Hes1, c-Src, and CSL. Immunofluorescence showed that endothelial cells in hypoxic culture began to express the α-SMA, and the expression of vWF increased with hypoxia. Cell viability, scratch, and transwell results showed that endothelial cells in the hypoxic group were more capable of viability and migration than those in the normoxic group. The induction of EnMT by hypoxia can be inhibited by using notch3-specific inhibitor DAPT and Jagged-1. This study also found that miR-7-5p can regulate endothelial NOTCH3, indicating that miRNA is also involved in the process of endothelial-mesenchymal transformation. Conclusion. Hypoxia promotes the transformation of endothelial cells into mesenchymal cells by opening the NOTCH3 pathway, which lays the foundation for disease progression or clinical prognosis, and is of great significance in the treatment of diseases. [ABSTRACT FROM AUTHOR]