Induction of trophinin in human endometrial surface epithelia by CGβ and IL‐1β

Abstract

During embryo implantation, trophinin mediates cell adhesion by homophilic binding at the apical surfaces of trophectoderm and endometrium. Trophinin is expressed on the human endometrial epithelia in rare occasions. We developed hCGcoated agarose beads that mimic the physical and physiological features of an implantation-stage human blastocyst. When hCG-coated beads were applied to human endometrial epithelial cells in the presence of IL-1b, endometrial cells acquired strong trophinin expression and the ability for apical cell adhesion with trophinin-expressing human trophoblastic cells. These results provide a mechanism for trophinin-mediated adhesion of human blastocyst to endometrium by a spatially and temporally restricted paracrine effect of hCG derived from the blastocyst.

Trophinin-mediated cell adhesion induces apoptosis of human endometrial epithelial cells through PKC-δ

“…5 Trophininexpressing primary cultured endometrial cells exhibited apical adhesion to HT-H cells. 5 When GWRQ was added to trophininexpressing primary cultured human endometrial epithelial cells, we observed apoptosis (Fig. 1D).…”

“…[2][3][4][5]7,9 In the first trimester placenta, invasive extravillous cytotrophoblasts confront the endometrial glandular epithelia, initiating the steps required for blood vessel formation of the placenta. 22 Trophinin expression by extravillous cytotrophoblasts (Sup.…”

“…Trophinin expression by endometrial epithelia is induced by human chorionic gonadotrophin (hCG) derived from trophoblastic cells of the implanting embryo. 4,5,7 Previously, we defined the mechanism underlying activation of trophectoderm cells of the blastocyst, which is triggered by trophinin-mediated cell adhesion using human embryonal carcinoma cell line HT-H. 9 The trophinin cytoplasmic domain forms a complex with bystin, 10 which arrests the epidermal trophinin is an intrinsic membrane protein expressed in trophectoderm cells of embryos and in uterine epithelial cells. trophinin potentially mediates apical cell adhesion at human embryo implantation sites through trophinin-trophinin binding in these two cell types.…”

“…1 Consequently, at least some mechanisms underlying embryo implantation are unique to humans. [2][3][4][5][6] Trophinin is an intrinsic membrane protein expressed on apical plasma membranes in human trophoblastic cells and endometrial epithelial cells, which mediates homophilic cell adhesion at respective apical cell surfaces. 7,8 Trophinin is not expressed in human endometrial epithelia throughout the hormonal cycle, except only those cells located close to the implanting blastocyst or the implantation site may express trophinin.…”

The actors of human implantation: gametes, embryo and endometrium

“…At the first steps of implantation, hCG is able to prolong the WOI, by inhibiting decidual Insulin like Growth Factor (IGF)-Binding Protein and IGFI (both markers of complete decidualization) (Fluhr et al, 2008b), and in association with interleukin 1 (IL-1), to favor adhesion via the increase in trophinin expression on endometrial epithelium (Sugihara et al, 2008). Concerning trophoblast functions hCG (and its hyperglycosylated variant) has been demonstrated to promote trophoblastic cells migration, and to reduce endometrial barrier, through its action on matrix metalloprotease protein 9 (MMP9, increased), TIMP-1, -2, -3 (reduced), GM-CSF, IL-11 Fluhr et al, 2008a;Paiva et al, 2011).…”