PLAC8 Expression Regulates Trophoblast Invasion and Conversion into an Endothelial Phenotype (eEVT)

TL;DR

PLAC8 affects how trophoblast cells invade and change into endothelial-like cells, which could influence pregnancy complications like preeclampsia.

Contribution

The study reveals PLAC8's dual role in promoting trophoblast invasion while inhibiting endothelial differentiation.

Findings

PLAC8 overexpression increases trophoblast invasion but reduces endothelial-like differentiation.

PLAC8 modulates vasculogenic factors like VEGF, PGF, and ANGPT2.

Hypoxia increases PLAC8 expression, linking oxygen tension to its regulation.

Abstract

PLAC8, expressed by interstitial extravillous trophoblasts (iEVTs), plays a crucial role in trophoblast invasion, differentiation, and immunotolerance. Its dysregulation may contribute to pregnancy complications, such as preeclampsia. This study investigates the role of PLAC8 in trophoblast invasiveness and endothelial-like differentiation under different oxygen tensions. Swan-71 cells were transiently transfected with PLAC8 overexpression or knockdown plasmids. Invasion was assessed using Matrigel-coated transwells, endothelial-like differentiation through tube formation assays, and vasculogenic marker expression (VEGF, PGF, ANGPT2) by RT-PCR. Hypoxia experiments were performed at different oxygen conditions. PLAC8 overexpression enhanced trophoblast invasion but reduced endothelial-like differentiation, downregulating VEGF and PGF while upregulating ANGPT2. Hypoxia increased PLAC8 expression, indicating oxygen tension as a regulatory factor. PLAC8 manipulation did not affect cell viability. PLAC8 modulates trophoblast behavior by promoting invasion while inhibiting endothelial-like differentiation. Its regulation of vasculogenic and angiogenic factors suggests a critical role in placental homeostasis and potential relevance to pregnancy disorders, such as preeclampsia.

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