Activin A regulates trophoblast cell adhesive properties: implications for implantation failure in women with endometriosis-associated infertility  

Oleh:

Stoikos, Chelsea J. ; Salamonsen, Lois A. ; Hannan, Natalie J.

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: Human Reproduction vol. 25 no. 07 (Jul. 2010), page 1767-1774.
Topik: human endometrium; activin A; implantation; integrins; endometriosis

Ketersediaan

Perpustakaan FK Nomor Panggil: H07.K.2010.03 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

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Isi artikel

BACKGROUND During implantation, the embryo adheres to the endometrium via cell adhesion molecules (CAMs) present on blastocyst trophectoderm and endometrial epithelial cells. CAMs, including integrins and extracellular matrix (ECM) ligands, are most likely regulated by hormones, cytokines and growth factors. We hypothesized first that activin A affects the adhesive properties of trophoblast cells and second that alterations in dimeric activin A levels in the uterine cavity could disrupt adhesion, thereby causing implantation failure. METHODS This study examined effects of activin A on trophoblast cell adhesion and measured activin A levels in secretory phase uterine washings from women with and without endometriosis (EOS). Activin receptor expression on trophoblast (HTR8) cells was examined by RT–PCR, and adhesive molecules measured by integrin antibody and cell–matrix adhesion assays. Dimeric activin A was measured (enzyme-linked immunosorbent assay) in uterine washings (14 controls and 23 EOS), and ßA-subunit localization was verified in endometrial tissues. RESULTS Activin receptors are expressed by HTR8 cells. Activin A activated Smad2 in a concentration-dependent manner which was blocked by an activin receptor inhibitor (SB431542). Following activin A treatment (50 ng/ml for 24 h), trophoblast cell surface integrins a1 a2 a3 a5, ß1, ß2, ß4 and avß5 were decreased, as was cell binding to the ECM ligands, fibronectin, collagen IV and collagen I (P < 0.05). Activin A was detected in 56.5% of EOS and 21.4% of control washings, with measured levels from 42 to 8481 pg/ml (not significantly different). CONCLUSIONS Decreased trophoblast CAM production and adhesion could be caused by dysregulated local activin A levels and may contribute to implantation failure. This could explain, in part, the infertility observed in women with EOS.

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