Invasive depth of extravillous trophoblast correlates with cellular phenotype: a comparison of intra- and extrauterine implantation sites

Abstract

During intrauterine human placentation, extravillous trophoblast invades uterine tissues starting with proliferating stem cells at the basement membrane of anchoring villi. Transition to the postproliferative invasive phenotype takes place several cell layers distant. Here we show that in intrauterine pregnancies invasive trophoblast comprises three cellular phenotypes: a. Small spindle-shaped trophoblast cells are found along the whole invasive pathway throughout pregnancy. They are embedded in little heterogeneous extracellular matrix but expose only fibronectin receptors (integrins alpha5beta1, alphavbeta3/5), resulting in a partial integrin-matrix mismatch. b. Large polygonal trophoblast cells are rare in early pregnancy but increase in number towards term. They secrete ample heterogeneous extracellular matrix and expose integrins specifically matching the opposing matrix molecules (integrins alpha6beta4, alpha5beta1). c. Multinucleated giant cells in all stages of pregnancy form a kind of peripheral shell of trophoblast. In contrast to intrauterine pregnancies, in viable tubal pregnancies, Mib-1 expression indicating proliferation, extends deeply into the invasive pathway. Trophoblast cells of the invasive pathway mostly belong to the small spindle-shaped phenotype and secrete little extracellular matrix, mainly fibronectins. At the transition to the second cellular layer of cell columns expression of integrin alpha6beta4 switches to expression of alpha5beta1 and alphavbeta3/5. Viable tubal pregnancies are characterised by a broad overlap of proliferative with invasive phenotype as well as a general integrin-matrix mismatch. The differences in proliferation patterns, cellular phenotype and matrix-integrin co-localisation may well explain the increase of invasiveness of normal extravillous trophoblast from term intrauterine via early intrauterine to viable tubal pregnancies.

Ectopic Pregnancy and Assisted Reproductive Technologies: A Systematic Review

“…In extrauterine pregnancy, expression of integrin subunit 3 is nearly exclusively restricted to the basal plasmalemma of the first layer of trophoblast cells while only the first proximal layer of EVT (in direct contact to the basement membrane) expresses integrin 6. The switch to the integrin subunits v and 5 takes place already in the second layer of trophoblast cells, as soon as the latter detach from the basement membrane (Kemp et al, 2002). In tubal pregnancies, MMP-9 and TIMP-1, -2 and -3 are produced by all types of extravillous cytotrophoblast (EVCT) cells, while MMP-2 and -14 mainly exist in distal column cytotrophoblast (CCT) cells and invasive EVCT cells (Bai et al, 2005).…”

Apoptosis placentaria: mecanismos moleculares en la génesis de la preclampsia

“…Esta población celular se genera a partir de las células del CTB de las vellosidades de anclaje (9). Luego que estas células proliferan, adquieren un fenotipo invasor por medio del cual desempeñarán su principal función: invadir el estroma uterino y luego las arterias espiraladas del endometrio, para así remodelar las paredes vasculares (12,13). De esta manera participan en la transformación de un circuito de alta resistencia al flujo sanguíneo en uno de baja resistencia (14).…”

Galectin-1 and functional properties of human trophoblast cells in vitro

“…Invazivni put diferencijacije intersticijalnog trofoblasta završava se formiranjem jednojedarnih krupnih poliploidnih EVT ćelija i višejedarnih džinovskih ćelija placentnog ležišta [2, [48][49][50][51][52]. Prema Kempu, poliploidne EVT ćelije su gotovo neinvazivne i nalaze se isključivo unutar bazalne ploče, gde proizvode vanćelijski matriks sastavljen uglavnom od laminina (LN), fibronektina (FN), kolagena tipa IV, vitronektina (VN) i heparan sulfata [50]. Njihov broj počinje naglo da raste tokom druge polovine trudnoće, pa neposredno pred porođaj one predstavljaju najbrojnije EVT ćelije.…”

“…Invazivni profil intersticijalnog trofoblasta uključuje ekspresiju α5β1, α1β1, ανβ1, ανβ3 i ανβ5, dok je α6β4 integrin potpuno odsutan [39,50,77,78] Kontrola trofoblastne proliferacije, diferencijacije i invazije se ostvaruje autokrinim, jukstakrinim i parakrinim mehanizmima, i uključuje različite faktore rasta, citokine, hemokine, kao i promene u parcijalnom pritisku kiseonika [2, 107,108]. Tako je pokazano da pored navedenih decidualnih faktora (IGF-II, IGFBP-1 i TGF-β), još neki faktori trofoblastnog i decidualnog porekla (epidermalni fakor rasta -EGF, transformišući faktor rasta alfa -TGF-α, itd.)…”