Severe pre-eclampsia is associated with alterations in cytotrophoblasts of the smooth chorion.

T Garrido-Gomez,S J Fisher,C Simón,M Gormley,M Kapidzic,K Ona,O Genbacev

doi:10.1242/dev.146100

Abstract

Pre-eclampsia (PE), which affects ∼8% of first pregnancies, is associated with faulty placentation. Extravillous cytotrophoblasts (CTBs) fail to differentiate properly, contributing to shallow uterine invasion and deficient spiral artery remodeling. We studied the effects of severe PE (sPE) on the smooth chorion portion of the fetal membranes. The results showed a significant expansion of the CTB layer. The cells displayed enhanced expression of stage-specific antigens that extravillous CTBs normally upregulate as they exit the placenta. Transcriptomics revealed the dysregulated expression of many genes (e.g. placental proteins, markers of oxidative stress). We confirmed an sPE-related increase in production of PAPPA1, which releases IGF1 from its binding protein. IGF1 enhanced proliferation of smooth chorion CTBs, a possible explanation for expansion of this layer, which may partially compensate for the placental deficits.

Highlights

Human placentation involves a remarkable series of interactions between embryonic/fetal trophoblasts and maternal cells (Burton and Jauniaux, 2015; Maltepe and Fisher, 2015)
We studied the effects of severe PE on the smooth chorion portion of the fetal membranes
The results showed a significant expansion of the CTB layer

Summary

Introduction

Human placentation involves a remarkable series of interactions between embryonic/fetal trophoblasts and maternal cells (Burton and Jauniaux, 2015; Maltepe and Fisher, 2015). In most of the villous placenta (chorion frondosum), cytotrophoblasts (CTBs) fuse to form a multinucleated epithelium that is perfused with maternal blood. They are ideally positioned to transport growth-promoting substances to the embryo/fetus, which they exchange for spent material. Near the uterine wall, CTBs adopt a different fate They leave the villi, forming columns of mononuclear cells, which anchor the placenta to the uterus, which they subsequently invade. They open up the spiral arteries, enabling placental perfusion, which substantially increases as they line and enlarge these vessels.

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