This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Kaitu'u-Lino, T. J. Articles by Salamonsen, L. A. Search for Related Content PubMed PubMed Citation Articles by Kaitu'u-Lino, T. J. Articles by Salamonsen, L. A. Pubmed/NCBI databases Substance via MeSH Medline Plus Health Information Menstruation

A New Role for Activin in Endometrial Repair after Menses

Prince Henry’s Institute of Medical Research (T.J.K.-L., N.B.M., L.A.S.) and Department of Obstetrics and Gynecology (T.J.K.-L.) and Monash Institute of Medical Research (D.J.P.), Monash University, Clayton, Victoria 3168, Australia

Address all correspondence and requests for reprints to: Lois Salamonsen, Prince Henry’s Institute of Medical Research, Level 4, Block E, Monash Medical Centre, 246 Clayton Road, Clayton, Victoria 3168, Australia. E-mail: Lois.salamonsen{at}princehenrys.org.

Abnormal uterine bleeding can severely affect the quality of life for women. After menstruation, the endometrium must adequately repair to limit and stop bleeding. Abnormal uterine bleeding may result from incorrect or inadequate endometrial repair after menstruation. Previous studies have shown an important contribution of activin to skin wound healing, with severely delayed wound repair observed in animals transgenically induced to overexpress activin’s natural inhibitor, follistatin. Activin subunits have also been identified within human endometrium; however, their role in endometrial repair is unknown. We assessed the contribution of activin to endometrial repair after menses using a human in vitro cell wounding method and our well-characterized mouse model of endometrial breakdown and repair applied to mice overexpressing follistatin. Endometrial repair after menses is initiated with reepithelialization of the uterine surface. To mimic this repair, we utilized a human endometrial epithelial cell line (ECC-1) and demonstrated significant stimulation of wound closure after activin A administration, and attenuation of this response by addition of follistatin. Immunolocalization of activin subunits, βA and βB, in control endometrium from the mouse model demonstrated specific epithelial and stromal localization and some leukocyte staining (βA) around sites of endometrial repair, suggestive of a role for activin in this process. Follistatin-overexpressing animals had significantly higher circulating follistatin levels than wild-type littermates. There was a significant delay in endometrial repair after breakdown in follistatin transgenic animals compared with control animals. This study demonstrates for the first time a functional role for activin in endometrial repair after menses.