Expression of Hepatocyte Growth Factor and Its Receptor c-metin the Ovine Uterus1

Abstract

Epithelial-mesenchymal interactions (EMI) are necessary for epithelial cell proliferation, differentiation, and function in the uterus and are mediated, in part, by paracrine growth factors of stromal origin. The objective of this study was to determine if hepatocyte growth factor (HGF, scatter factor) and its receptor c-met were present in the ovine uterus and to characterize their temporal and spatial expression during the estrous cycle and pregnancy. Reverse transcription-polymerase chain reaction was used to clone partial cDNAs for ovine HGF and c-met from endometrial total RNA. Northern blot analysis of endometrial RNA revealed expression of a 6-kb mRNA for HGF and an 8-kb mRNA for c-met in ovine endometrium. In situ hybridization demonstrated that HGF mRNA was expressed by stromal cells of the endometrium, whereas c-met mRNA was localized exclusively to luminal and glandular epithelial cells. In the early conceptus, HGF mRNA was expressed by chorioallantoic mesenchyme, and c-met was expressed by trophectoderm. Steady-state levels of endometrial c-met mRNA increased after Day 9 in both cyclic and pregnant ewes. The HGF mRNA was expressed during both the estrous cycle and early pregnancy. Results indicate that HGF is a stromal-derived paracrine growth factor in the ovine uterus and placenta that is potentially involved in endometrial epithelial-stromal interactions and chorioallantoic stromal-trophectodermal interactions. In the ovine uterus, HGF may stimulate epithelial morphogenesis and differentiated function required for establishment and maintenance of pregnancy, conceptus implantation, and placentation.