Keratinocyte growth factor and its receptor in the rhesus macaque placenta during the course of gestation

Keratinocyte growth factor (KGF) is synthesized and secreted exclusively by mesenchymal cells, and acts through its receptor (KGFR) to stimulate epithelial proliferation. In vivo, KGF and KGFR comprise a mesenchymal-epithelial cell paracrine system that can mediate epithelial cell mitosis. In preliminary work, we noted that KGF was expressed in the rhesus monkey placenta, and we now report on the expression of placental KGF and KGFR mRNAs during the course of gestation in this species. In-situ hybridization revealed that during early gestation, KGF mRNA was strongly expressed in placental mesenchymal cells. These cells, which were also immunoreactive for vimentin, were mainly located on the periphery of the mesenchymal cores of both anchoring and floating villi. KGFR mRNA was expressed in the adjacent trophoblastic epithelium, which was immunoreactive for cytokeratin. In-situ hybridization revealed that KGF mRNA expression was very high in the youngest placentae (34-days gestation) and decreased gradually to minimal levels by late gestation (157 days). Northern blot analysis indicated also that the KGF MRNA signal was strongest in early gestation samples and weakest by late gestation. Analysis for KGFR mRNA by a reverse transcriptase-polymerase chain reaction technique showed that KGFR mRNA expression could be detected at all stages. However, in-situ hybridization indicated that KGFR mRNA expression was highest in early gestation placentae and least in the oldest placentae. Autoradiographs of frozen sections of placenta that had been incubated with [125I]KGF to detect receptor binding showed that grain density over the trophoblast was highest in the youngest and least in the oldest placentae. PCNA and Ki-67 expression followed this same temporal trend. We conclude that the KGF/KGFR system may be important in proliferation of the placental trophoblast during early- to mid-pregnancy in rhesus monkeys.