MicroRNAs: key regulators of the trophoblast function in pregnancy disorders

Abstract

The placenta is essential for a successful pregnancy and healthy intrauterine development in mammals. During human pregnancy, the growth and development of the placenta are inseparable from the rapid proliferation, invasion, and migration of trophoblast cells. Previous reports have shown that the occurrence of many pregnancy disorders may be closely related to the dysfunction of trophoblasts. However, the function regulation of human trophoblast cells in the placenta is poorly understood. Therefore, studying the factors that regulate the function of trophoblast cells is necessary. MicroRNAs (miRNAs) are small, non-coding, single-stranded RNA molecules. Increasing evidence suggests that miRNAs play a crucial role in regulating trophoblast functions. This review outlines the role of miRNAs in regulating the function of trophoblast cells and several common signaling pathways related to miRNA regulation in pregnancy disorders.

Keywords: MicroRNAs; Placenta; Pregnancy disorders; Trophoblast cells.

Fig. 1

Remodeling of normal and abnormal spiral arteries. Extravillous trophoblast cells widen the inner diameter of the artery through invasion and migration, completing the remodeling of the spiral artery. Dysregulation of extravillous trophoblast cell migration and invasion can lead to failure of spiral arterial remodeling and inadequate fetal nutrition. ICM, inner cell mass; CTBs, cytotrophoblasts; STB, syncytiotrophoblast; iEVTs, interstitial extravillous trophoblast cells; enEVTs, extravillous trophoblast cells; NK, natural killer cell; DSC, decidual stromal cells

Fig. 2

TGF-β pathway, MAPK pathway, and PI3K/AKT pathway. MiRNAs regulate trophoblast biological functions through TGF-β pathway, MAPK pathway, and PI3K/AKT pathway. TGF-β, transforming growth factor β; BMP, bone morphogenetic protein; GDF, growth and differentiation factor; SMAD, Sma- and Mad-related protein; ActRIIA, activin type IIA receptor; ActRIIB, activin type IIB receptor; TGF-βRII, transforming growth factor-beta receptor II; BMPR2, bone morphogenetic protein receptor-2; MAPK, mitogen-activated protein kinase; ERK, extracellular signal-regulated kinase; JNK, c-Jun NH2-terminal kinase; MAP3K, MAPK kinase; MAP2K, MAPK kinase; MLK3, mixed-lineage kinase 3; ASK1, apoptosis signal-regulating kinase 1; MEKK1, MEK kinase 1; PI3K, phosphatidylinositol-3-kinase; AKT, protein kinase B; PTEN, tensin homolog