Development of the hemochorial maternal vascular spaces in the placenta through endothelial and vasculogenic mimicry

Abstract

The maternal vasculature within the placenta in primates and rodents is unique because it is lined by fetal cells of the trophoblast lineage and not by maternal endothelial cells. In addition to trophoblast cells that invade the uterine spiral arteries that bring blood into the placenta, other trophoblast subtypes sit at different levels of the vascular space. In mice, at least five distinct subtypes of trophoblast cells have been identified which engage maternal endothelial cells on the arterial and venous frontiers of the placenta, but which also form the channel-like spaces within it through a process analogous to formation of blood vessels (vasculogenic mimicry). These cells are all large, post-mitotic trophoblast giant cells. In addition to assuming endothelial cell-like characteristics (endothelial mimicry), they produce dozens of different hormones that are thought to regulate local and systemic maternal adaptations to pregnancy. Recent work has identified distinct molecular pathways in mice that regulate the morphogenesis of trophoblast cells on the arterial and venous sides of the vascular circuit that may be analogous to specification of arterial and venous endothelial cells.

Placental Evolution within the Supraordinal Clades of Eutheria with the Perspective of Alternative Animal Models for Human Placentation

“…However, our functional and experimental understanding of placentation in comparison to the human is largely due to the mouse model (Mus musculus) as by far the best investigated species in that regard. Even though it is not the aim of this contribution to repeat the astonishing amount of data on mouse placentation, so far special reference has been given to the early establishment of the placenta, the associated genes and cell lineages, relevant knock out models, and in regard to common pregnancy disorders such as fetal miscarriage, preeclampsia, or intrauterine growth restriction (e.g., [18,70,71,[180][181][182][183][184][185][186][187][188][189][190][191][192][193][194]). Also, several studies deal with placental aspects in the laboratory rat Rattus norvegicus (e.g., [70,71,[195][196][197][198][199][200][201][202][203][204][205][206]).…”

HIF-KDM3A-MMP12 regulatory circuit ensures trophoblast plasticity and placental adaptations to hypoxia

“…Invasive trophoblast cells arise from trophoblast stem (TS)/progenitor cell populations and can be classified based on their entry into the uterine parenchyma (5,6). Endovascular invasive trophoblast cells enter uterine spiral arteries, facilitate removal of the endothelium, acquire a pseudovascular phenotype, and restructure the spiral artery, whereas interstitial invasive trophoblast cells migrate into a specialized uterine stroma, termed decidua, and infiltrate areas surrounding the spiral arteries (2,4,7,8). These seminal events in hemochorial placentation are conserved in the rat and human (9)(10)(11).…”

Genomic imprinting, growth and maternal–fetal interactions

“…These organisms share similar placental physiology: both use a hemochorial placenta where the maternal blood travels through sinusoidal spaces lined by trophoblast cells, rather than an endothelium, allowing for more efficient nutrient transfer (reviewed in Rai and Cross, 2014). The distinct populations of cells in the placenta, the trophoblast and the extraembryonic mesoderm, differentiate early in embryogenesis with the trophoblast cells invading the maternal uterine decidua following fertilisation.…”

“…The portion of the placenta where maternal and fetal circulation is closely opposed is known as the labyrinth in mice. The trophoblast further differentiates into multiple cell types that have both endocrine and energy-storage properties (Rai and Cross, 2014).…”