A Novel In Vitro Model of Trophoblast-Mediated Decidual Blood Vessel Remodeling

Abstract

SUMMARY:In vivo the extravillous trophoblasts (EVTs) penetrate the decidua and the first third of the myometrium to remodel the uterine spiral arteries and achieve the high-flow, low-resistance circulation characteristic of the intervillous space of the term placenta. Much of our understanding of these processes comes from histologic analysis of placental bed biopsies, a limited tissue source and one that can provide only a snapshot of a dynamic process. To better characterize these cellular interactions, we have developed an in vitro co-culture system in which first trimester villous explants are cultured at low oxygen tension in contact with 2-mm 2 sections of decidua parietalis from the same patient. Hematoxylin eosin counterstaining of paraffin sections shows that EVT columns form at the tips of the placental villi and adhere and penetrate the decidual surface. The decidual blood vessels in the path of the EVT show morphologic disruption. Immunohistochemical analysis of the co-cultures using both an endothelial specific anti-CD31 and an anti-smooth muscle actin antibody show a disruption of the integrity of the vessel lining together with a complete loss of organized smooth muscle actin surrounding the blood vessels. In contrast control decidua samples in the absence of placental villi exhibit blood vessels with a complete endothelial lining and an organized muscular sheath. Using both an anti-cytokeratin-7 and anti-Cdx-2 antibody specific to trophoblasts, we show that these changes coincide with invasion of the vessels by endovascular trophoblasts and penetration of the decidua by interstitial EVTs. No EVTs were found in the control decidua. Thus we conclude that this in vitro model mimics the physiologic change observed in vivo during trophoblast invasion into maternal decidual tissues, and as such it may provide useful information concerning the interactions between EVTs and decidual cells and vessels during early gestation. (Lab Invest 2003, 83:1821-1828.

Evidence for Immune Cell Involvement in Decidual Spiral Arteriole Remodeling in Early Human Pregnancy

“…[17][18][19] Neutrophil depletion in a mouse model of menstruation demonstrates these leukocytes have an essential role in endometrial breakdown and repair. 20 Using a novel in vitro model recreating the early pregnancy placental-decidual interface, 21,22 we have evidence for leukocyte infiltration of the vessel wall during active remodeling and before the appearance of vEVT (published in abstract form 23 ). Extensive disorganization and apoptotic loss of VSMC and endothelial cells was apparent, coincident with leukocyte infiltration.…”

Efeito do extrato de Mikania glomerata Sprengel (guaco) sobre a implantação e o desenvolvimento embrinário e placentário em camundongos.

“…(CROSS et al, 2002;DUNK et al, 2003;GEUSENS et al, 2008). Este mecanismo diminui a resistência vascular e impede a ação de mediadores vasoativos na interface materno-fetal, garantindo um suprimento sanguíneo (nutrientes e gases) adequado ao desenvolvimento do concepto (CROSS., 2005;PLAISIER., 2011;PIJINENBORG et al, 2011).…”

Spiral Artery Remodeling in Preeclampsia Revisited

“…Rather than focusing on trophoblast invasion studies in cell culture that model interstitial invasion, we need to adopt better in vitro models to recapitulate the vascular changes noted in the myometrium. In this regard, in vitro models developed by Cartwright et al 15 and Dunk et al 16 allow adequate manipulation of the myometrial system. Both groups use biopsy samples to dissect out myometrial arteries for various experiments.…”