Temporal expression and location of colony-stimulating factor 1 (CSF-1) and its receptor in the female reproductive tract are consistent with CSF-1-regulated placental development

Abstract

During pregnancy the mouse uterine epithelial synthesis of the mononuclear phagocyte growth factor designated colony-stimulating factor 1 (CSF-1) is regulated by female sex steroids. To study the role of CSF-1 in the pregnant female reproductive tract, the temporal expression and cellular sites of synthesis of CSF-1 and CSF-1 receptor (CSF-1R) mRNA were determined. CSF-1 mRNA, predominantly the 2.3-kilobase (kb) form, was first detected by in situ hybridization in uterine epithelium prior to implantation on day 3 and subsequently increased, reaching a peak at days 14-15. Its expression was restricted to the uterine epithelium at all stages of gestation and was not localized to areas of implantation. CSF-1R mRNA was first detected in maternal decidua at day 6. It was expressed in the decidua basalis during placentation, after which its expression declined. At day 7.5, trophectodermal cells also expressed CSF-1R mRNA; during placentation, it was found also in the diploid trophoblasts. The high level of CSF-1R mRNA expression by trophoblast giant cells was independent of their location around the conceptus. There was a differential distribution of CSF-1R mRNA expression in the mature placenta, with expression in the giant trophoblastic layer greater than spongiotrophoblastic layer greater than labyrinthine layer until term. Yolk sac cells also expressed low levels of CSF-1R mRNA. The coincidence of uterine CSF-1 mRNA expression and CSF-1 synthesis with both placental growth and CSF-1R mRNA expression in decidual cells and trophoblasts strongly implicates CSF-1 in the regulation of placental growth and differentiation.