Placenta-Specific miR-125b Overexpression Leads to Increased Rates of Pregnancy Loss in Mice.

Fen Sun,Jian Zhang,Lunbo Tan,Hui Cai,Jinlian Hua,Xiujun Fan,Dezhe Qin,Sha Peng

doi:10.3390/ijms23020943

Abstract

Pregnancy loss (PL) is one of the common complications that women can experience during pregnancy, with an occurrence rate of 1 to 5%. The potential causes of pregnancy loss are unclear, with no effective treatment modalities being available. It has been previously reported that the level of miR-125b was significantly increased in placentas of PL patients. However, the role of miR-125b in the development of PL still remains unknown. In the current study, an miR-125b placenta-specific over-expression model was constructed by lentiviral transfecting zona-free mouse embryos followed by embryo transfer. On gestation day 15, it was observed that the placenta was significantly smaller in the miR-125b placenta-specific overexpression group than the control group. Additionally, the abortion rate of the miR-125b placenta-specific overexpression group was markedly higher than in the control group. The blood vessel diameter was larger in the miR-125b-overexpressing specific placenta. In addition, miR-125b-overexpressing HTR8 and JEG3 cell lines were also generated to analyze the migration and invasion ability of trophoblasts. The results showed that miR-125b overexpression significantly suppressed the migration and invasion ability of HTR8 and JEG3 cells. Overall, our results demonstrated that miR-125b can affect embryo implantation through modulating placenta angiogenesis and trophoblast cell invasion capacity that can lead to PL.

Highlights

Publisher’s Note: MDPI stays neutralSuccessful reproduction is both biologically and epidemiologically complex, while the loss of a pregnancy following conception is a commonly observed event
Vascular endothelial growth factor (VEGF) can serve as an important target gene of miR-125b that has been closely related to placental angiogenesis and trophoblast cell invasion [26]
The findings indicated that miR-125b could significantly affect placenta angiogenesis by inhibiting VEGF expression, and could possibly lead to the development of novel treatment modality for Pregnancy loss (PL)

Summary

Introduction

Successful reproduction is both biologically and epidemiologically complex, while the loss of a pregnancy following conception is a commonly observed event. PL is the most common pregnancy-associated complication. It is defined as the two or more continuous pregnancy losses in the first or early second trimester of gestation. The various causes of spontaneous abortion in females have been generally identified, including environmental factors, genetics, endocrine, placental anomalies, hormonal problems, infections and psychological trauma [3]. In approximately half of the patients with spontaneous abortion, the causes are still unclear

Methods

Results

Discussion

Conclusion