Endocrine Abstracts

At implantation, the ability of an embryo to successfully attach to the luminal epithelium is dependent on the receptive phenotype the endometrium must acquire. This spatially and temporally restricted period of uterine receptivity is defined by endometrial molecular adaptations, highly regulated by embryonic-derived signals and ovarian steroids. Critical to this isthe expression of adhesivemoleculesintegrins and osteopontin (OPN) at the foetal-maternal interface which facilitate initial embryo-endometrial interactions. Osteopontinis the primary ligand for αvβ3 integrinwhich show coordinateincreased mid-luteal expression. Aims of this study were to characterise spatio-temporal expression and steroidal regulation of osteopontin and αvβ3 in ovine endometrium.

Sheep uteri obtained from intact mid-luteal and follicular phase and from ovariectomised ewes subjected to intramuscularinjections of 12.5 mg/ml progesterone±3 μg/ml oestradiol for 10 days, commencing 6 days following ovariectomy. Molecular analysis of osteopontin and αvβ3 and its αv and β3 subunits was performed by RT-PCR and immunohistochemistry.

Cycle-dependent changes in osteopontin and αvβ3 were confirmed, with an increase in OPN and β3 subunit in mid-luteal phase endometrium.Peak levels of OPN transcript notable in mid-luteal inter-carunculartissue, indicates abundance of glands in these regions are likely the primary source of OPN endometrial production. Progesterone treatment induced an increase in OPN mRNA and protein, most significantly in glandular epithelium. The cellular distribution of αv subunit was comparable to osteopontin, although levels of transcript and protein were shown to peak in follicular phase and were induced most significantly in response to oestradiol. The spatial and temporal distribution pattern of β3 subunit differed to αv with no detectable staining in either luminal or glandular epithelium, but strong immunoreactivity was consistent in both phases in vasculature and increasedin subepithelialstroma in mid-luteal phase compared to follicular. In conclusion, mid-luteal up-regulation of OPN and αvβ3 may facilitate early embryo attachment.

Declaration of funding: This work was supported and is part of an ongoing Phd. project, by the BBSRC.