NK cells, hypoxia and trophoblast cell differentiation

Abstract

Hemochorial placentation is characterized by extensive remodeling of the maternal vasculature, converting them to flaccid low resistance vessels. This process greatly facilitates exchange of nutrients and gases between the mother and the fetus. Two key modulators that orchestrate these vascular changes have been identified at the maternal fetal interface, natural killer (NK) cells and invasive trophoblast cells. Hypoxia-inducible factor (HIF) transcription factors direct cellular responses to low oxygen, influencing trophoblast lineage commitment and promoting development of the invasive trophoblast lineage. This short review focuses on role of NK cells on uterine spiral artery development and subsequent modulation of oxygen tensions at the maternal fetal interface.

Figure 1. Schematic diagram showing the role of NK cells and hypoxia/HIF signaling in the regulation of trophoblast cell differentiation. NK cells regulate uterine vascular development, which impacts oxygen delivery (ΔO₂) and trophoblast lineage decisions. Differentiated trophoblast lineages in the labyrinth zone include syncytial trophoblast. Differentiated trophoblast lineages in the junctional zone include trophoblast giant cells, spongiotrophoblast cells, glycogen cells and precursors for invasive trophoblast cells.