Human Trophoblast Invasion and Spiral Artery Transformation

Abstract

During early human pregnancy extravillous cytotrophoblasts invade the uterus and also migrate up the spiral arteries, transforming them into large vessels of low resistance. Failure of transformation has been described in pre-eclampsia, fetal growth restriction, and miscarriage. Recent evidence suggests that some maternal vessels undergo structural changes without interaction with cytotrophoblasts. The possibility arises that local vasoactive mediators such as nitric oxide result in spiral artery dilatation before their invasion. In support of this, a recent histological study in the guinea pig suggested that cytotrophoblasts expressed nitric oxide synthase (NOS) as they surrounded vessels. This study tested the hypothesis that invading cytotrophoblasts express NOS and therefore have the potential to induce vasodilatation by releasing nitric oxide. The expression of NOS on extravillous cytotrophoblasts was studied in placental bed biopsies, obtained, using a transcervical sampling technique, from normal human pregnancies between 8 to 19 weeks of gestation and in the third trimester. Whereas eNOS was expressed by syncytiotrophoblast, neither eNOS or iNOS was expressed by extravillous cytotrophoblasts at any time during invasion. The mechanisms controlling spiral artery transformation are pivotal to understanding normal and abnormal placentation. These results suggest that trophoblast-derived nitric oxide is unlikely to contribute to spiral artery dilatation.

Decreasing resistance in the maternal uterine and peripheral arterial system is apparently unrelated to plasma and urinary levels of nitrite/nitrate and cyclic-guanosinmonophosohate during the course of normal pregnancies

“…Our findings support the reports of Lyall and Robson that the cytotrophoblast derived NO is unlikely to contribute to the spiral artery dilation [10]. That NO-production is increased only in certain compartments [e.g.…”

“…These gradual processes finish with the second trophoblast invasion with direct opening of the spiral arteries in the intervillous space [9]. The transformation is characterized by a gradual loss of the normal musculoelastic structure of the arterial wall [10]. This phenomenon is reflected in the disappearance of the early diastolic notch and in a decrease in resistance index and pulsatility index of the uterine arteries until 24 weeks of gestation.…”

Does endothelial cell activation occur with intrauterine growth restriction?

“…Pre-eclampsia and fetal growth restriction have both been attributed to a failure of trophoblast invasion which leads to underperfusion of the uteroplacental bed 1 . However, why one pregnancy with a failure of trophoblast invasion is complicated by pre-eclampsia alone, another with fetal growth restriction alone and yet another with both, is not known.…”

Efeitos da inibição da sintase induzida do óxido nítrico na fisiopatologia da pré-eclâmpsia experimental

“…Os trofoblastos são as células precursoras da placenta humana, cujas funções (implantação embrionária, produção de hormônios gestacionais, proteção imunológica fetal, aumento do fluxo sanguíneo vascular materno na placenta, parto, etc.) são críticas para o sucesso da gravidez (Lyall, Bulmer et al, 1999).…”

“…No processo de invasão dessas células ocorre remodelamento gradual da camada endotelial destes vasos e destruição do tecido elástico-muscular das artérias e arteríolas tornando-as mais dilatadas (Lyall, Bulmer et al, 1999;Redman e Sargent, 2005). Esta migração/diferenciação dos citotrofoblastos deve-se a alterações nos perfis de expressão de certas citocinas, moléculas de adesão, constituintes da matriz extracelular, metaloproteinases e o antígeno de histocompatibilidade (HLA-G) (Roberts, Taylor et al, 1991).…”