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

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.