Blastocyst implantation precedes induction of insulin-like growth factor II gene expression in human trophoblasts

The cytotrophoblast cell population of the human embryonic conceptus proliferates rapidly during the first month following blastocyst implantation. Since the trophectoderm lineage is established in preimplantation morula/blastocysts, the scenario underlying initiation and maintenance of the rapid proliferative phenotype of cytotrophoblasts is a central issue. The insulin-like growth factor II (IGF-II) gene is highly expressed in proliferative cytotrophoblasts of first trimester placenta and performs as a placenta growth factor. To establish a temporal correlation between IGF-II expression and initiation of highly proliferative trophoblasts in human development, we employed in situ hybridization analysis of the expression of the IGF-II and human chorionic gonadotropin beta-subunit (beta-HCG) genes in human pre- and postimplantation development. The data show that the appearance of high steady-state levels of IGF-II transcripts in trophoblasts is a postimplantation event, whereas beta-HCG transcripts can already be detected in preimplantation development. This observation makes a role for endogenously produced IGF-II in the normal development of preimplantation embryos unlikely, but suggests that endogenously produced IGF-II participates in the formation and subsequent expansion of the rapid proliferative phenotype of the trophoblastic shell, following implantation.