Regulatory pathways controlling the endovascular invasive trophoblast cell lineage

Abstract

Hemochorial placentation is characterized by trophoblast-directed uterine spiral artery remodeling. The rat and human both possess hemochorial placentation and exhibit remarkable similarities regarding the depth of trophoblast invasion and the extent of uterine vascular modification. In vitro and in vivo research methodologies have been established using the rat as an animal model to investigate the extravillous/invasive trophoblast lineage. With these research approaches, two signaling pathways controlling the differentiation and invasion of the trophoblast cell lineage have been identified: i) hypoxia/hypoxia inducible factor and ii) phosphatidylinositol 3-kinase/AKT/Fos like antigen 1. Dissection of these pathways has facilitated identification of fundamental regulators of the invasive trophoblast cell lineage.

Fig. I

Hypoxia signaling and activation of the invasive trophoblast cell lineage and trophoblast cell-directed uterine spiral artery remodeling. Panel A} Effects of maternal hypoxia on placentation. Exposure to maternal hypoxia increases uterine vascularity, endovascular invasive trophoblast cell invasion, and cellular allocation to the junctional zone of the chorioallantoic placenta. Panel B) Schematic representation of the effects of oxygen tension on TS cells and HIF-dependent trophoblast cell 1ineage decisions.

Fig. 2

PBK/AKT/FOSLI pathway regulating the invasive trophoblast cell lineage and trophoblast cell-directed uterine spiral artery remodeling. Disruptions in the PJ3K/AKT/FOSLI pathway leads to pregnancy related disease, including early pregnancy loss, preeclampsia, pre-term birth, and intrauterine growth restriction (IUGR).