Identification and characterization of keratinocyte growth factor in the porcine uterus

The uterine growth, development and functional changes for the successful establishment and maintenance of pregnancy requires coordinated actions of various hormones and growth factors. Among many growth factors affected by steroid hormones, keratinocyte growth factor (KGF) is suggested to mediate progesterone action on uterine endometrial epithelial function in a paracrine manner in epithelial-mesenchymal interactions. Therefore, this research was conducted to determine: (1) effects of day and pregnancy status on KGF gene expression in the porcine uterine endometrium; (2) factors regulating KGF expression; and (3) function of KGF in the porcine uterus.; The first study determined if KGF and its receptor (KGFR), were expressed in the porcine uterus as a potential paracrine system. The KGF gene was expressed solely by endometrial epithelia and was particularly abundant between Days 12 and 15 of the estrous cycle and pregnancy. KGFR was expressed in both endometrial epithelia and conceptus trophectoderm. KGF secretion into the lumen of the porcine uterus was detected on Day 12 of the estrous cycle and pregnancy.; The second study determined factors affecting KGF gene expression in the uterus and role of KGF on conceptus trophectoderm. Endometrial explants were cultured in the presence of estradiol-17beta, catechol estrogens, or progesterone. Slot blot analyses revealed that estradiol-17beta increased KGF expression; catechol estrogens did not affect KGF expression; and progesterone slightly decreased KGF expression. KGF significantly increased proliferation of porcine trophectoderm cells as well as affected their differentiation.; The third study determined effects of interleukin-1beta on KGF expression and KGF on endometrial epithelial cells in vivo and in vitro. Increasing doses of interleukin-1beta decreased KGF expression. In vivo administration of KGF did not affect proliferation and expression of several differentiation markers in the endometrial epithelia.; Collectively, these results demonstrate that KGF gene expression in endometrial epithelial cells is increased by estradiol-17beta of conceptus origin and that KGF stimulates both proliferation and differentiation of conceptus trophectoderm. These results suggest that KGF plays a crucial role in epithelial-epithelial interactions between conceptus and uterus during early pregnancy in pigs, which is the only species possessing a true epitheliochorial type of placentation.