Cytotrophoblast differentiation in the first trimester of pregnancy: evidence for separate progenitors of extravillous trophoblasts and syncytiotrophoblast

Abstract

It is commonly accepted that a single pool of villous cytotrophoblasts are precursors of both syncytiotrophoblast and extravillous trophoblasts during the first trimester. Here we present evidence that these two trophoblast subpopulations arise from separate progenitors that have different survival characteristics when studied in villous explant cultures. Dual staining with chloromethylfluorescin diacetate and ethidium bromide revealed degeneration of the syncytiotrophoblast by non-apoptotic mechanisms within 4 h of culture. The syncytiotrophoblast had regenerated within 48 h but at this point the vast majority of the cytotrophoblast and cells of the mesenchymal core were dead. Despite this extensive cytotrophoblast death, explants are able to produce extravillous trophoblast outgrowth for up to 3 weeks in culture. We believe that the villous cytotrophoblasts in the tips of anchoring villi are resistant to the factors that cause the death of the majority of villous cytotrophoblasts in culture. We speculate that as early as 8 weeks of gestation there are two separate villous cytotrophoblast populations, one committed to differentiate into syncytiotrophoblast and the second committed to the extravillous differentiation pathway

Quantifying trophoblast migration: In vitro approaches to address in vivo situations

“…However, like primary EVTs, the villous explant tissue itself has a limited period of viability in culture, meaning that outgrowth expansion can only be tracked for a few days. 31 …”

Isolation and characterisation of a novel trophoblast side-population from first trimester placentae

“…However, when cultured, isolated villous cytotrophoblasts (even from early gestation placentae) differentiate to form the multinucleated syncytiotrophoblast (Dodeur et al 1990). Furthermore, work by ourselves and others has suggested that rather than existing as one homogenous bipotent population, cytotrophoblast subpopulations are primed to differentiate into either syncytiotrophoblast or extravillous trophoblast (Aboagye-Mathiesen et al 1996, James et al 2005, Telugu et al 2013. Indeed, many epithelial stem cell populations have the ability to generate committed progenitors, referred to as transit amplifying cells, which are able to expand the progenitor pool in tissues with rapid growth or high turnover (Blanpain et al 2007).…”

Role of placenta-specific protein 1 in trophoblast invasion and migration

“…These trophoblast cells interact with the uterus and produce functional factors to modify maternal physiological systems, and render enough blood flow and nutrients to the fetal-maternal interface (Burrows et al 1996, Lyall et al 1999, Watson & Cross 2005, Osol & Mandala 2009). In the villous tips which contact the maternal decidua, the cytotrophoblast (CTB) progenitor cells can develop and break the syncytiotrophoblast (STB) layer, assemble as the extravillous trophoblast column (TC), and further invade into the decidua to form EVTs (James et al 2005). The proximal portion of TC maintains their proliferative abilities, while trophoblast cells from the distal part invade into the decidua and even deeper into the myometrium, in order to achieve appropriate remodeling of maternal spiral artery and better anchor the fetus to the uterus (Osol & Mandala 2009).…”