Human Trophoblast Invasion and Spiral Artery Transformation

Abstract

During early human pregnancy extravillous cytotrophoblasts invade the uterus and spiral arteries transforming them into large vessels of low resistance. Failure of trophoblast invasion and spiral artery transformation occurs in preeclampsia and fetal growth restriction (FGR); these processes are not well understood. Recent studies have suggested that cytotrophoblasts that invade spiral arteries mimic the endothelial cells they replace and express PECAM-1. It was also reported that in preeclampsia, cytotrophoblasts fail to express PECAM-1 and that failure to express endothelial cell adhesion molecules may account for failed trophoblast invasion. Despite the possible importance of adhesion molecules in trophoblast invasion, no study has systematically investigated the expression of PECAM-1 in the placental bed throughout the period of invasion, particularly in the myometrial segments where the key failure occurs. There are no studies on PECAM-1 expression in the placental bed in FGR. We have examined the expression of PECAM-1 in placental bed biopsies and placentas from 8 to 19 weeks of gestation and in the placenta and placental bed in the third trimester in cases of preeclampsia, FGR, and control pregnancies. PECAM-1 was expressed on endothelium of vessels in the placenta and placental bed but not by villous or extravillous trophoblasts in normal or pathological samples. These findings do not support a role for PECAM-1 in normal invasion or in the pathophysiology of preeclampsia or FGR.

Oxygen tension regulates the miRNA profile and bioactivity of exosomes released from extravillous trophoblast cells – Liquid biopsies for monitoring complications of pregnancy

“…While the precise mechanisms involved in uterine spiral artery remodeling have yet to be established, interstitial and perivascular EVT have been implicated. EVT migrate into the maternal decidua and myometrium from 12–16 weeks of gestation in association with vascular remodeling [28]. Furthermore, it has been proposed that inadequate invasion of EVT into the myometrium is associated with a failure to remodel uterine spiral arteries.…”

Elevated maternal serum sP-selectin levels in preeclamptic pregnancies with and without intrauterine fetal growth restriction, but not in normotensive pregnancies complicated by isolated IUGR

“…Reduced uteroplacental perfusion in preeclamptic pregnancies is associated with endothelial dysfunction, which is one of the causes leading to the failures of trophoblast invasion and spiral artery transformation, and which results in an impaired placentation [8]. In preeclamptic pregnancies there are no inadequate physiologic changes of spiral arteries remodeling.…”

“…It was suggested that an important factor for proper trophoblast invasion and vascular remodelling is the expression and activity of adhesion molecules [8,15,16]. …”

MBL Interferes with Endovascular Trophoblast Invasion in Pre-Eclampsia

“…These changes, that include gradual loss of the musculoelastic structure of the arterial wall and replacement by amorphous fibrinoid material, are essential to create vessels of low resistance unresponsive to vasoconstrictive agents [1, 2] allowing continuous blood flow in the intervillous space. …”