Upregulation of RND3 Affects Trophoblast Proliferation, Apoptosis, and Migration at the Maternal-Fetal Interface

Abstract

Trophoblasts as the particular cells of the placenta play an important role in implantation and formation of the maternal-fetal interface. RND3 (also known as RhoE) is a unique member of the Rnd subfamily of small GTP-binding proteins. However, its function in cytotrophoblasts (CTBs) at the maternal-fetal interface is poorly understood. In the present study, we found that RND3 expression was significantly increased in trophoblasts from the villous tissues of patients with recurrent miscarriage (RM). RND3 inhibited proliferation and migration and promoted apoptosis in HTR-8/SVneo cells. Using dual-luciferase reporter and chromatin immunoprecipitation assays, we found that forkhead box D3 (FOXD3) is a key transcription factor that binds to the RND3 core promoter region and regulates RND3 expression. Here, the level of FOXD3 was upregulated in the first-trimester CTBs of patients with RM, which in turn mediated RND3 function, including inhibition of cell proliferation and migration and promotion of apoptosis. Further, we found that RND3 regulates trophoblast migration and proliferation via the RhoA-ROCK1 signaling pathway and inhibits apoptosis via ERK1/2 signaling. Taken together, our findings suggest that RND3 and FOXD3 may be involved in pathogenesis of RM and may serve as potential therapeutic targets.

Effect of IL-15-Mediating IFN-γ on HTR-8/SVneo Cells and a Preeclampsia Mouse Model Induced by Lipopolysaccharides

“…During pregnancy, the apoptosis of trophoblasts in placental tissues has important functions in migratory and invasive abilities, which are critical for pregnancy success [27][28][29]. Excessive placental trophoblast apoptosis may apparently reduce cell migration and invasion and cause shallow placental implantation and insufficient remodeling of the uterine spiral artery, eventually inducing the occurrence of PE [30,31].…”

Tissue‐resident CD8+T memory cells with unique properties are present in human decidua during early pregnancy

“…In our study, we mainly focused on detecting TGF‐β1 expressed in DSCs and trophoblasts. We did not further distinguish the subsets of trophoblasts due to the low proportion of EVT 86‐90 . Trophoblasts also can produce a similar level of TGF‐β1 as DSCs but failed to upregulate the expression of CD103 on CD69 + CD8 + T cells.…”

“…We did not further distinguish the subsets of trophoblasts due to the low proportion of EVT. [86][87][88][89][90] Trophoblasts also can produce a similar level of TGF-β1 as DSCs but failed to upregulate the expression of CD103 on CD69 + CD8 + T cells. We speculated that the different secretion of TGF-β1 between trophoblast and DSCs, and the shortage of time on coculturing may lead to this result.…”

Crosstalk Between Trophoblasts and Decidual Immune Cells: The Cornerstone of Maternal-Fetal Immunotolerance

“…Trophoblasts are the only fetal-derived cells that come into close contact with the mother's immune system. Moderate proliferation, migration and invasion of trophoblasts in early pregnancy are crucial to placenta formation and fetal growth, and are regulated by multiple factors (4,5). Dysfunction of trophoblast cells may lead to a series of pregnancy-related complications including RSA and preeclampsia (PE) (6,7).…”