THE EXPRESSION OF INSULIN-LIKE GROWTH-FACTOR (IGF) AND IGF-BINDING PROTEIN (IGFBP) GENES IN THE HUMAN PLACENTA AND MEMBRANES - EVIDENCE FORIGF-IGFBP INTERACTIONS AT THE FETOMATERNAL INTERFACE

The placenta synthesizes insulin-like growth factors (IGFs) and their binding proteins (IGFBPs), which are believed to regulate its growth a nd development in an autocrine/paracrine manner. To delineate the cell ular sites of expression of IGF and IGFBP messenger ribonucleic acids (mRNAs) in human placenta throughout pregnancy we used in situ hybridi zation histochemistry with S-35-labeled IGF and IGFBP complementary RN A probes on human placentas and fetal membranes of gestational ages 6 weeks to term (40 weeks). In placental regions where trophoblasts (fet al) or decidua (maternal) coexist (e.g. basal plate), the identity was delineated by their cytokeratin or vimentin immunoreactivity, respect ively. Except for IGF-II, mRNAs encoding peptides of the IGF system we re expressed in a similar spatial pattern and relative abundance throu ghout gestation. Both IGF mRNAs showed similar tissue distribution, bu t the IGF-II mRNA was more abundant than IGF-I mRNA at all gestational ages. IGF-II mRNA was expressed in the chorionic mesoderm of placenta l villi and chorionic plate in moderate abundance, and it decreased wi th gestation. It was also expressed in the trophoblasts of the cytotro phoblastic shell and Langhan's layer of placental villi only in the fi rst trimester, suggesting an autocrine role for IGF-II in early cytotr ophoblastic proliferation and/or differentiation. IGF-II mRNA was expr essed most abundantly in the columns of intermediate trophoblasts in t he anchoring villi and chorionic and basal plates. A gradient of IGF-I I mRNA abundance was observed in the trophoblasts of the cytotrophobla stic column, with greater IGF II mRNA levels in those at the invading front, suggesting a role for IGF-II in trophoblastic invasion. In the fetal membranes, IGF-II mRNA was identified in the amnion and chorion laeve. IGF-I receptor mRNA was expressed in low abundance in all cell types of the placenta. All six IGFBP mRNAs were identified in variable abundance in the decidualized stromal cells of the maternal decidua b asalis and parietalis, with IGFBP-1 mRNA being expressed in the greate st abundance. The spatial pattern of expression of each IGFBP mRNA als o differed among decidual cells, with IGFBP-1, IGFBP-2, IGFBP-4, and I GFBP-6 mRNAs being expressed in most cells, whereas IGFBP-3 and IGFBP- 6 mRNAs were expressed in only some cells. IGFBP-1 mRNA was expressed initially in the epithelium of endometrial glands and in a population of decidualized stromal cells in early gestation, and subsequently in the majority of decidualized stromal cells. IGFBP-3 mRNA was expressed in both the decidua and certain intermediate trophoblasts of the basa l plate and anchoring villi of placenta and in amnion and chorion laev e of fetal membranes. IGFBP-4 and IGFBP-5 mRNA were expressed addition ally in low abundance in the chorionic mesoderm. IGFBP-6 was expressed in greater abundance in the decidua parietalis than in decidua basali s, although the general level of expression was low. The spatial patte rn and relative abundance of expression of IGFBP mRNAs suggest IGFBP-1 to be the predominant IGFBP synthesized by the maternal decidual cell s, interacting with the IGF-II that synthesizes fetal intermediate tro phoblasts. Presumably, IGF-II and IGFBPs are used for cell to cell com munication between fetal trophoblasts and maternal decidual cells at t he fete-maternal interface for placental development and/or function.