Expression and regulation of integrin receptors in human trophoblast cells: Role of estradiol and cytokines

Abstract

<span style="font-size:14.0pt;line-height: 115%;font-family:" times="" new="" roman";mso-fareast-font-family:"times="" roman";="" mso-ansi-language:en-in;mso-fareast-language:en-in;mso-bidi-language:hi"="" lang="EN-IN">Embryo implantation and placentation are dynamic cellular events that require not only synchrony between the maternal environment and the embryo, but also complex cell-cell communication amongst the implanting blastocyst and the receptive endomatrium through integrins, a large family of proteins involved in the attatchment, migration, invasion and control of cellular functions. Integrins display dynamic temporal and spatial patterns of expression by the trophoblast cells during early pregnancy in humans. However, the precise mechanism of embryo implantation and the modulation of the integrin receptors during blastocyst attachment and further implantation remin elusive in the humans. The present study elucidates the expression and hormonal modulation of fibronectin, vitronectin and laminin integrin receptors by estradiol and IL-1α in human trophoblast cells. Human first trimester trophoblast cells showed the induction of the classical estrogen receptor (ER)-α by its own ligand ,estradiol. Treatment with either estradiol or IL- 1α induced the expressions of α₄α₅α₆ and α_v, integrin receptor subunits at both the mRNA and protein levels, while expression of β₁ remained unaltered. Furthermore estradiol upregulated the expression of IL- 1α, thereby suggesting the possibility that estrogen may either directly or via the proinflammatory cytokine induces the expression of the cell surface integrin receptors. The findings delineate the role of hormones and the cytokines in modulating the adhesiveness and attatchment of the trophoblast cells. This may reflect the <i>in vivo</i> scenario where the implanting embryo is surrounded by a hormone-cytokine rich uterine microenvironment that may preisely regulate the expression of integrins and thereby facilitate implantation.</span>