INSULIN-LIKE-GROWTH-FACTOR BINDING-PROTEIN GENE-EXPRESSION IN THE PREGNANT RAT UTERUS AND PLACENTA

While the insulin-like growth factor (IGF) system plays a fundamental role in regulating embryonic and placental growth, the specific contri butions of the six IGF binding proteins (IGFBPs 1-6) to these processe s are not well understood. We here focus on IGFBP expression in the ex traembryonic environment, which both supports and constrains embryonic growth, and have used in situ hybridization to determine sites of IGF BP mRNA synthesis in the pregnant rat uterus and placenta. We find tha t all IGFBPs are expressed in distinct, changing patterns in the uteri ne endometrium, at the decidual boundary, in the decidual vasculature, and in the myometrium during pregnancy. Within the endometrium, the m ost prominent change is that expression of IGFBP-1 begins in some, but not all, endometrial glands prior to implantation and then expands to include all secretory epithelia shortly after implantation. During th e period of rapid decidual proliferation that follows implantation, IG FBP-3, -4, and -5 transcripts are all detected in a laminar array at t he boundary between the decidua and the nondecidualized endometrium. I n the decidual vasculature at Day (d) 8.0, both IGFBP-3 and IGFBP-4 mR NAs are detected in dilating blood vessels, with BP-3 most prominent i n the antimesometrial plexus and BP-4 primarily at the mesometrial pol e. Later (d11.5), all decidual vessels express high levels of IGFBP-3 and lower levels of IGFBP-4 mRNAs. Finally, changes in expression of s everal IGFBPs also occur within the myometrium during pregnancy. For e xample, IGFBP-2 is expressed in the inner circular layer shortly after implantation, and expression increases through late gestation. In con trast, IGFBP-5 hybridization occurs over both myometrial layers before implantation, but decreases in intensity and spatial distribution as pregnancy proceeds. finally, and most strikingly, IGFBP-6 expression, barely detectable in the d7.0 myometrium, gradually increases until it is very strongly transcribed during the placental stages. Taken toget her, these observations suggest multiple roles for IGFBPs in supportin g implantation, regulating the extent of decidualization, modulating l ocal levels of vascular IGFs, and regulating uterine muscular growth. (C) 1997 Academic Press.