Mol. Hum. Reprod. Advance Access originally published online on March 21, 2008
Molecular Human Reproduction 2008 14(5):301-307; doi:10.1093/molehr/gan016
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Activin A increases invasiveness of endometrial cells in an in vitro model of human peritoneum
1Department of Obstetrics and Gynecology, University of Texas Health Science Center, San Antonio, TX, USA 2Department of Obstetrics and Gynecology, University of Minas Gerais, Av. Alfredo Balena 110–9o andar, 30130-100 Belo Horizonte, MG, Brazil 3Department of Physiology, University of Minas Gerais, Av. Alfredo Balena 110–9o andar, 30130-100 Belo Horizonte, MG, Brazil 4Department of Pediatrics, Obstetrics and Reproductive Medicine, University of Siena, Siena, Italy
5 Correspondence address. Tel: +55-31-3248-9485; Fax: +55-31-3248-9299; E-mail: reis{at}medicina.ufmg.br
The aim of this study was to investigate whether activin A has an effect on the attachment and/or invasion of endometrial cells in a modeled peritoneum in vitro. Cultured endometrial stromal cells (ESCs) and endometrial epithelial cells (EECs) were treated with activin A (6.25–50 ng/ml) and with activin A (25 ng/ml) with and without inhibin A or follistatin. Fluorescent labeled cells were added to confluent peritoneal mesothelial cells (PMCs) and to a monolayer of confluent PMCs grown in a MatrigelTM invasion assay. The rate of endometrial cell attachment and invasion through PMCs was assessed. The expression of cell adhesion proteins N- and E-cadherin was evaluated with real-time RT–PCR. Activin A (25 ng/ml) promoted invasion of the endometrial cells through the modeled peritoneum (>2-fold versus control) and this effect was partially reversed by inhibin A and follistatin. Activin A had no effect on the rate of attachment of the endometrial cells to the PMCs or in the rate of proliferation. In addition, activin A induced a decreased mRNA expression of E-cadherin in cultured EECs. In conclusion, activin A increases invasion of EECs and ESCs into modeled peritoneum. In EECs, this effect may be related to down-regulation of E-cadherin expression. Further studies are warranted to evaluate the role of activin-A in the genesis of the endometriotic lesion.
Key words: activin A/inhibin A/follistatin/endometriosis/cadherins
Presented, in part, at the 62nd Annual Meeting of the American Society for Reproductive Medicine, New Orleans, October 2006. Submitted on January 7, 2008; resubmitted on March 3, 2008; accepted on March 5, 2008.