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 β-subunit (β-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 β-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.

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