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Vertebrate reproductive science and technology
RESEARCH ARTICLE

216. Activin A regulates trophoblast cell adhesion: implications for uterine receptivity and embryo implantation

C. J. Stoikos A B , A. O.’Connor C , L. A. Salamonsen A and E. Dimitriadis A
+ Author Affiliations
- Author Affiliations

A Prince Henry's Institute of Medical Research, Clayton, Vic., Australia.

B Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria 3, Clayton, Vic., Australia.

C Monash Institute of Medial Research, Clayton, Victoria, 3168, Australia., Clayton, Vic., Australia.

Reproduction, Fertility and Development 20(9) 16-16 https://doi.org/10.1071/SRB08Abs216
Published: 28 August 2008

Abstract

Embryo implantation involves blastocyst attachment to the endometrial luminal epithelium, followed by trophoblast invasion. This process involves a coordinated crosstalk between the implanting blastocyst and the endometrium. Adhesion molecules play an instrumental role during implantation and are regulated by a variety of factors including cytokines and growth factors. Activin A, a TGF-β superfamily member, has been detected in uterine washings,1 and its subunit, β A, is produced by endometrial glands during the secretory phase of the menstrual cycle.2 In endometriosis, a disease that associated with sub-fertility, β A immunostaining is increased in endometrial glands,3 suggesting higher levels of activin A secreted into the uterine lumen could contribute to sub-fertility observed in endometriosis. Therefore we hypothesised that activin A secretion into the uterine cavity affects the adhesive properties of the cells present at the maternal-fetal interface. The aims of the study were to measure and compare activin A secretion in uterine washings from women with and without endometriosis and to demonstrate whether activin A regulates adhesion to extracellular matrix (ECM) components. Uterine washings (5 mL of sterile saline) were collected from women with and without endometriosis during the secretory phase. Activin A was measured by ELISA. HTR8 (human trophoblast cell-line) cells were treated with rhActivin A (50 ng/mL) and assessed for binding to fibronectin, laminin, vitronectin, collagen I and IV. Activin A (>10pg/mL) was detectable in uterine washings from women with and without endometriosis and levels were elevated in endometriosis patients. Untreated HTR8 cells adhered maximally to fibronectin, collagen I and collagen IV with low binding to vitronectin and laminin. Following activin treatment, HTR8 cell binding to fibronectin, collagen I and IV was significantly decreased (n = 3, P < 0.05). These results suggest that activin A regulates the adhesive properties of the blastocyst during implantation. This study also implies that abnormalities in local activin A levels during endometrial receptivity may contribute to sub-fertility in women.

(1) Petraglia et., al. (1998) J Clin Endocrinol Metab.

(2) Jones et., al. (2000) Mol Hum Reprod.

(3) Rombauts et., al. (2006) Aust N Z J Obstet Gynaecol.