Oxygen as modulator of trophoblast invasion

Abstract

At the time of blastocyst implantation the uterine spiral arteries have already undergone morphological changes in the absence of any extravillous trophoblast invasion. Only 2 weeks after implantation, extravillous trophoblast cells develop and come into first contact with decidual tissues. Invading through the decidual interstitium, extravillous trophoblasts potentially reach and transform spiral arteries into uteroplacental arteries. Spiral arterial erosion starts at about mid-first trimester, whereas flow of maternal blood into the intervillous space is continuously established only at the beginning of the second trimester. One key regulator of the number of extravillous trophoblasts is oxygen. The steep gradient in oxygen concentration within the first trimester placenta is diminished with the onset of maternal blood flow. This gradient is used by the trophoblast to generate a large number of invasive cells to adapt the arterial vasculature in the placental bed to the growing needs of the fetus. Changes in oxygen concentrations or other factors leading to alterations in the rates of proliferation and/or apoptosis of extravillous trophoblast clearly impact on the remodelling of the vessels. The respective consequences of a failure in trophoblast invasion are growth restrictions of the baby and perhaps other pregnancy complications.

Placental hypoxic overlap lesions: A clinicoplacental correlation

“…The test has been proposed as a screening tool for early‐onset fetal growth restriction in the first and second trimesters and as a means of segregating small fetuses with abnormal placentas (fetal growth restriction) from the physiologically small fetuses with healthy placentas, that is, small for gestational age fetuses . Although abnormal Doppler indices are suboptimal measures for the purpose, in this analysis they were strongly associated with placental abnormalities (maternal underperfusion or fetal vascular obstruction, and abnormal trophoblast invasion) . Although other authors reported a single histological pathology with no overlap of lesions (maternal underperfusion 50%, and fetal vascular obstructive lesions 27%) in most cases of fetal growth restriction (88%) regardless of the Doppler results, this analysis (Table ) showed strong association of abnormal umbilical artery Dopplers and placental hypoxic overlap lesions.…”

Increased immortalization‐upregulated protein 2 (IMUP‐2) by hypoxia induces apoptosis of the trophoblast and pre‐eclampsia

“…Hypoxic conditions are necessary for promotion of trophoblast invasion into the myometrium of the maternal uterus during early pregnancy; subsequently, an inadequate oxygen supply induces stress and apoptosis of the trophoblast, which can lead to pre‐eclampsia [Lash et al, 2007; Huppertz et al, 2009]. Hypoxia‐inducible factor (HIF‐1) induced by hypoxic conditions is a transcriptional activator that regulates expression of several genes in response to oxygen tension [Dunwoodie, 2009].…”

VariableDAXXgene methylation is a common feature of placental trophoblast differentiation, preeclampsia, and response to hypoxia

“…Identification of HIF1A signaling as a pathway that shows low methylation in EVCTs relative to CTBs is of particular interest because of the important role oxygen tension plays in trophoblast differentiation and invasion. We hypothesized that the location of EVCTs at the proximal part of the cell column, where oxygen levels are lowest (33), results in the hypo‐methylated profile of these genes. Further study of the role of DNA methylation in HIF1 signaling in trophoblast development is warranted.…”