MicroRNA-184 promotes apoptosis of trophoblast cells via targeting WIG1 and induces early spontaneous abortion

Yuan Zhang,Jin-Ping Zhang,Jie Xu,Ji Zhou,Ming-Qing Li,Li-Ping Jin

doi:10.1038/s41419-019-1443-2

Abstract

Recurrent spontaneous abortion (RSA) refers to the unintentional termination of two or more consecutive pregnancies that severely threatens human reproductive health. Our previous study has shown that miR-184 is expressed more highly in RSA than in normal pregnancy, whether in the villus or decidua. In this study, compared with normal pregnant women, the expression of miR-184 in decidual stromal cells (DSCs) and decidual immune cells (DICs), as well as in peripheral blood, from RSA patients was enhanced similarly. Moreover, we found miR-184 could promote the apoptosis and repress the proliferation of trophoblast cells. Further exploration indicated that miR-184 upregulated the expression of Fas by targeting WIG1 thus inducing cell apoptosis. Finally, after miR-184 overexpression in vivo, the embryo resorption rate in pregnant mice was increased significantly. Therefore, our study outlines the pivotal role of miR-184 in maintaining successful pregnancy, providing a new diagnostic and therapeutic target for RSA.

Highlights

As an embryo allograft, successful pregnancy needs the maternal immune system to recognize but not reject the fetal alloantigen[1]
The expression of miR-184 is increased in Recurrent spontaneous abortion (RSA) patients Based on the expression profiling of miRNAs at the maternal-fetal interface[11], miR-184 exists in both the decidua and villus, the expression of which was higher in RSA than in normal pregnancy
After isolation from the decidua of RSA and normal pregnancy, the expression of miR-184 in decidual stromal cells (DSCs) and decidual immune cells (DICs) was examined by real-time polymerase chain reaction (RT-PCR), confirming that miR-184 was highly expressed in DSCs and DICs of RSA (Fig. 1a, b)

Summary

Introduction

Successful pregnancy needs the maternal immune system to recognize but not reject the fetal alloantigen[1]. Other than known pathogenic factors, including chromosomal abnormalities, endocrinological factors, and immune dysfunction, still almost half of the causes of RSA are unclear and further explanation is urgently needed[3]. As the main constituent cells of human placenta, embryo-derived trophoblast cells proliferate, MicroRNAs (miRNAs) are a group of small non-coding RNAs composed of 20–24 nucleotides. By binding to the 3’ untranslated region (3’ UTR) of target messenger RNAs. Official journal of the Cell Death Differentiation Association. (mRNAs), miRNAs induce target mRNA degradation or inhibit its translation, participate in a wide range of biologic and pathologic processes, such as cell differentiation, proliferation, apoptosis, angiogenesis, and even inflammation[8,9]. Previous studies have found that abnormal expression of miRNAs is closely related to reproductive system diseases, including endometriosis, preeclampsia, and infertility. CYR61, a key regulator for wound recovery, tumor growth, vascular disease, and embryo development, could be repressed by miR-155 and lead to preeclampsia[10]

Methods

Results

Conclusion