Expression of paracrine growth factors and their receptors in the ovine uterus

Abstract

Epithelial-mesenchymal interactions 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 potential candidates fibroblast growth factor-7 (FGF-7), FGF-10, and hepatocyte growth factor (HGF), and their respective receptors, FGFR2IIIb and c-met, are present in the ovine uterus and to characterize their temporal and spatial expression during the estrous cycle and early pregnancy. An ovine FGF-10 cDNA was cloned from an ovine endometrial cDNA library. The ovine FGF-10 cDNA encodes a protein of 213 amino acids and possesses an unusually long 5' untranslated region (UTR). In situ hybridization demonstrated that ovine FGF-10 mRNA was expressed by endometrial stromal cells and by mesenchymal cells of the chorioallantoic placenta. The mRNA for FGF-7, a homologue of FGF-10, was localized in the tunica muscularis of blood vessels in endometrium and myometrium. In contrast, FGF receptor 2IIIb, the high affinity receptor for both FGF-10 and FGF-7, was expressed exclusively in luminal epithelium (LE), glandular epithelium (GE), and placental trophectoderm/chorion. The in vivo expression indicated that FGF-7 and FGF-10 are uterine stromal cell-derived mediators of uterine epithelial and conceptus trophectodermal functions. The nonoverlapping spatial patterns of expression for FGF-10 and FGF-7 in the ovine uterus and conceptus suggest that they have independent roles in uterine function and conceptus development. Partial cDNAs for ovine HGF and c-met were cloned. In situ hybridization analyses demonstrated that HGF mRNA was expressed by stromal cells of the endometrium, whereas c-met mRNA was localized exclusively to LE and GE. In the conceptus, HGF mRNA was expressed by chorioallantoic mesenchyme and c-met was expressed by trophectoderm. Results indicate that HGF, a stromal-derived paracrine growth factor, is present in the ovine uterus and placenta and potentially involved in endometrial epithelial-stromal interactions and chorioallantoic stromal-trophectodermal interactions. Collectively, FGF-7, FGF-10 and HGF are paracrine growth factors in the ovine uterus that act locally as stromal mediators of uterine epithelial cell function(s) during the estrous cycle and both uterine epithelial and trophectoderm/chorion functions during pregnancy.