Involvement of nephrin in human placental trophoblast syncytialization

Abstract

The placenta has numerous functions, such as transporting oxygen and nutrients and building the immune tolerance of the fetus. Cell fusion is an essential process for placental development and maturation. In human placental development, mononucleated cytotrophoblast (CTB) cells can fuse to form a multinucleated syncytiotrophoblast (STB), which is the outermost layer of the placenta. Nephrin is a transmembrane protein that belongs to the Ig superfamily. Previous studies have shown that nephrin contributes to the fusion of myoblasts into myotubes in zebrafish and mice, presenting a functional conservation with its Drosophila ortholog sticks and stones. However, whether nephrin is involved in trophoblast syncytialization remains unclear. In this study, we report that nephrin was localized predominantly in the CTB cells and STB of human placenta villi from first trimester to term pregnancy. Using a spontaneous fusion model of primary CTB cells, the expression of nephrin was found to be increased during trophoblast cell fusion. Moreover, the spontaneous syncytialization and the expression of syncytin 2, connexin 43, and human chorionic gonadotropin beta were significantly inhibited by nephrin-specific siRNAs. The above results demonstrate that nephrin plays an important role in trophoblast syncytialization.

Placental trophoblast syncytialization potentiates macropinocytosis via mTOR signaling to adapt to reduced amino acid supply

“…1 A and B) and hCGB (the gene encoding hCGβ) (Fig. 1C), the hallmarks of trophoblast syncytialization (15). STB formation proceeded over time as presented by immunostaining for E-cadherin and DAPI (Fig.…”

“…We reasoned that the trophoblast, especially the STB, could undergo macropinocytosis to keep energy homeostasis and support fast fetal growth in the uterus. First, we performed in vitro trophoblast syncytialization experiments by using two cell models, spontaneously formed STB from PHT cells or forskolin (FSK)-induced cell fusion in the trophoblast cell line BeWo (15). PHT cells, isolated from normal term placenta, fused spontaneously to form STB in 10% FBS-supplemented culture condition, as indicated by a gradually increased expression of Syncytin2 (Fig.…”

Oxidative stress-induced impairment of trophoblast function causes preeclampsia through the unfolded protein response pathway

“…Thus, increased levels of β-hCG and decreased Dysferlin expression observed in PE patients can be attributed to the generation of OS. Further, it is reported that Syncytin-2 is also associated with the immunosuppressive function 52 , a feature crucial for the survival of a semi-allogenic fetus in the maternal endometrial environment and to avoid maternal immune surveillance. Based on the above report, reduced expression of Syncytin2 in ROS-treated trophoblasts and in the placental explants in our study implies that ROS produced in the placental bed could perturb the immune homeostatic mechanisms.…”

APOL1-G0 or APOL1-G2 Transgenic Models Develop Preeclampsia but Not Kidney Disease

“…[44][45][46] Placental Nephrin expression has also been documented in other studies. [47][48][49] The pregnancy phenotype was not caused by an artifact of transgenesis, as none of the many published transgenic mouse lines created using the Nphs1 promoter have reported adverse pregnancy outcomes.…”