Placenta Trophoblast Fusion

Abstract

It has been known for more than 150 years that syncytial fusion is a normal feature in biological systems. In humans there are two larger syncytial tissues: skeletal muscles fibers and placental syncytiotrophoblast. Other fusion events take place as well from fertilization of the oocyte to infection of human cells by enveloped viruses (however, the latter does not necessarily lead to syncytium formation).Although knowledge of the fusion process is incomplete, it is clear that membranes do not fuse easily; specific proteins and other factors are required and are selectively activated. In this chapter, we describe the classic proteins, such as the syncytins, assumed to be involved in the fusion process. We also describe other factors that may play roles in the fusion process or in the preparation of the cells to fuse, such as charged phospholipids, divalent cations, and intracellular proteases. Finally, we speculate on why trophoblast cells fuse in vitro and deal with in vitro models of trophoblast fusion and how their fusion rates can be quantified.

Involvement of nephrin in human placental trophoblast syncytialization

“…When the expression of nephrin was knocked down, trophoblast syncytialization as well as the expression of syncytin 2 and connexin 43 was decreased. In the placenta, syncytin is located on the cell membrane and mediates placental CTB cell fusion by binding to the syncytin receptor (Mi et al 2000, Esnault et al 2008, Huppertz & Borges 2008, Vargas et al 2009). As a gap junctional protein, connexin 43 is required for CTB cell fusion into syncytia (Dunk et al 2012, Pidoux et al 2014.…”

“…Instead, it develops into the outermost layer of the placental villi, where it directly contacts maternal blood. During the remaining stages of pregnancy, the STB plays important functions in immune tolerance, the production of hormones such as human chorionic gonadotropin beta (b-hCG) and the exchange of nutrients and waste products (Malassine & Cronier 2002, Leisser et al 2006, Huppertz & Borges 2008. In the so-called secondary syncytialization, mononucleated cytotrophoblast (CTB) cells lining the placental villi fuse with the multinucleated STB.…”

Mechanism of Congenital Chagas Disease: Effective Infection Depends on the Interplay Between Trypanosoma cruzi and the Different Tissue Compartments in the Chorionic Villi of the Human Placenta

“…Between morula and blastocyst stages, the trophoblast lineage forms a cover around the early embryo (the embryoblast) (Berniscke et al, 2006;Huppertz and Borges, 2008). The human trophoblast differentiates into two major subtypes (Drewlo et al, 2008;Huppertz and Gauster, 2010;Huppertz and Borges, 2008): a) Cells that invade maternal uterine tissue and differentiate into the extravillous trophoblast, and b) Cells that remain within the placenta and differentiate into the villous trophoblast forming the epithelial cover of the placental villi and constituting part of the placental barrier (Berniscke et al, 2006;Kemmerling et al, 2010) (see Figure 1). The villous trophoblast is composed of two cellular layers: the syncytiotrophoblast (ST) and the cytotrophoblast (CT).…”

“…The CT displays high proliferative properties, whereas the differentiated ST loses its generative capacity and is no longer able to proliferate. The ST is a multinucleated layer that forms the outer surface of placental villi and comes into direct contact with maternal blood (Berniscke et al, 2006;Huppertz and Borges, 2008). This cell layer is a typical syncytium with plasma membranes only on the apical and basal sides.…”

“…b. Transcription factors: Glial cell missing-1 (GCM1), a placenta-specific transcription factor, regulates transcription via two GCM1 binding sites upstream the 5′-long terminal repeat of the syncytin-1 gene (Huppertz and Borges, 2008;Yu et al, 2002). GCM1 is expressed in highly differentiated CT cells (Baczyk et al, 2004;Huppertz and Borges, 2008).…”