Steroid regulation of secreted phosphoprotein 1 (SPP1) expression in ovine endometrium

Secreted phosphoprotein 1 (SPP1) is an extracellular matrix glycoprotein that is highly expressed at the maternal-fetal interface and is a critical mediator of embryo implantation. The objectives of this study were to examine the spatial and temporal cyclical expression patterns and steroid regulation of SPP1 mRNA and protein in ovine endometrium, which may be further indicative of their functionality in embryo implantation. Uterine tissue was obtained following hysterectomy from ovariectomised ewes treated with ovarian steroids. In parallel, invitro culture of endometrial cells was used to investigate the effects of ovarian steroids on SPP1 expression in endometrial and luminal epithelial (LE) cells. A significant sustained mid-luteal phase increase in SPP1 mRNA in intercaruncular regions of the endometrium was observed, indicating that glandular epithelium is likely to be the primary source of SPP1 production. This increase in SPP1 was induced by progesterone treatment and was shown at the protein level by immunohistochemistry analysis. Similarly, treatment of stromal cells with 10ng mL-1 progesterone or in combination with 1ng mL-1 oestradiol significantly increased SPP1 expression (P<0.05). Collectively, expression levels of SPP1 are cycle-dependent and peak in the progesterone-dominant luteal phase. They are dependent on the interaction of uterine LE and stromal cells and may involve paracrine signalling by progesterone receptor-positive stromal cells.