REVIEW ARTICLE: Governing the Invasive Trophoblast: Current Aspects on Intra‐ and Extracellular Regulation

Abstract

Citation Fitzgerald JS, Germeyer A, Huppertz B, Jeschke U, Knöfler M, Moser G, Scholz C, Sonderegger S, Toth B, Markert UR. Governing the invasive trophoblast: current aspects on intra‐ and extracellular regulation. Am J Reprod Immunol 2010This review summarizes several aspects especially of regulating factors governing trophoblast invasion. Those include the composition of the extracellular matrix containing a variety of matrix metalloproeinases and their inhibitors, but also intracellular signals. Furthermore, a newly described trophoblast subtype, the endoglandular trophoblast, is presented. Its presence may provide a possible mechanism for opening and connecting uterine glands into the intervillous space. Amongst others, two intracellular signalling pathways are crucial for regulation of trophoblast functions and development: Wnt‐ and signal transducer and activator of transcription (STAT)3 signalling. Wnt signalling promotes implantation, placentation and trophoblast differentiation. Several Wnt‐dependent cascades and regulatory mechanisms display different functions in trophoblast cells. The STAT3 signalling system is fundamental for induction and regulation of invasiveness in physiological trophoblastic cells, but also in tumours. The role of galectins (Gal) in trophoblast regulation and placenta development comes increasingly into focus. The Gal‐ 1–4, 7–10 and 12–14 have been detected in humans. Detailed information is only available for Gal‐1, ‐2, ‐3, ‐4, ‐9 and ‐12 in endometrium and decidua. Gal‐1, ‐3 and ‐13 (‐14) have been detected and studied in trophoblast cells.

An EG-VEGF-Dependent Decrease in Homeobox Gene NKX3.1 Contributes to Cytotrophoblast Dysfunction: A Possible Mechanism in Human Fetal Growth Restriction

“…ST differentiation can be reproduced in vitro using different models (7,(49)(50)(51), but BeWo cells exhibit a low spontaneous fusion rate that can be increased with FSK treatment (52). We demonstrated that FSK treatment increased NKX3.1 expression in BeWo cells, suggesting NKX3.1 may contribute to an optimum differentiation potential of trophoblasts.…”

Decreased STAT3 in human idiopathic fetal growth restriction contributes to trophoblast dysfunction

“…In several mouse malignancies, Stat3, the murine homolog of human STAT3, has been identified as an important regulator of genes that are central to cellular survival, proliferation and apoptosis (Johnston & Grandis 2011). Stat3 plays an important role in early embryogenesis by fostering the metabolic exchange between the embryo and placenta (Garcia et al 2007, Fitzgerald et al 2010. The biological effects of Stat3 have also been evaluated by targeted gene ablation in transgenic mice (Horvath 2000, Jiang et al 2009).…”

“…ST formation can be reproduced in vitro using different models (Fitzgerald et al 2010, Orendi et al 2010, Pidoux et al 2012. In this study, we used the human choriocarcinoma BeWo cell line as described previously (Orendi et al 2010) to study the effect of villous trophoblast differentiation on STAT3 expression.…”

Forkhead box a2 (FOXA2) is essential for uterine function and fertility

“…Consequently, connections between the glands and developing intervillous space of the placenta can be observed as early as day 17 postfertilization and persist throughout the first trimester (66). Similar to the invasion of spiral arteries, uterine glands are also occupied by extravillous trophoblast cells termed "endoglandular trophoblasts" (67)(68)(69)(70). They have been speculated to provide gland-derived nutrition to the embryo before the establishment of functional uteroplacental circulation at the end of the first trimester.…”