Expression of hepatocyte growth factor and its receptor c-met in the ovineuterus

Epithelial-mesenchymal interactions (EMI) are necessary for epithelial cell proliferation, differentiation, and function in the uterus and are mediate d, in part, by paracrine growth factors of stromal origin. The objective of this study was to determine if hepatocyte growth factor (HGF, scatter fact or) and its receptor c-met were present in the ovine uterus and to characte rize their temporal and spatial expression during the estrous cycle and pre gnancy. Reverse transcription-polymerase chain reaction was used to clone p artial cDNAs for ovine HGF and c-met from endometrial total RNA. Northern b lot 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 demo nstrated that HGF mRNA was expressed by stromal cells of the endometrium, w hereas c-met mRNA was localized exclusively to luminal and glandular epithe lial cells. In the early conceptus, HGF mRNA was expressed by chorioallanto ic mesenchyme, and c-met was expressed by trophectoderm, Steady-state level s of endometrial c-met mRNA increased after Day 9 in both cyclic and pregna nt 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 en dometrial epithelial-stromal interactions and chorioallantoic stromal-tro-p hectodermal interactions. In the ovine uterus, HGF may stimulate epithelial morphogenesis and differentiated function required for establishment and m aintenance of pregnancy, conceptus implantation, and placentation.