EXPRESSION OF IGF LIGAND AND RECEPTOR GENES DURING PREIMPLANTATION MAMMALIAN DEVELOPMENT

The temporal patterns of expression of genes encoding insulin-like growth factor (IGF) ligands and receptors during very early development have been investigated in several laboratories in several different mammalian species. Both reverse transcription-polymerase chain reaction (RT-PCR) and immunocytochemical techniques have been used to identify the time of appearance of gene transcripts or end-products. In preimplantation mouse embryos, IGF-II ligand and receptor gene activity is detectable as early as at the two-cell stage, the time when transcription from the embryonic genome is activated, but receptors for insulin and IGF-I are not detectable until the compacted eight-cell stage. Transcripts for insulin or IGF-I are not detectable in preimplantation mouse embryos, although the ligands are present in the reproductive tract. The pattern of IGF gene expression is not, however, identical in all mammalian species. In cow embryos, for example, transcripts for IGF-I and IGF-II ligands and receptors and insulin receptors have been detected at all stages of preimplantation development from mature oocyte to blastocyst (Watson et al., 1992). Attempts to quantitate transcript abundance in these early embryos are in progress in our laboratory. In the preimplantation mouse embryo, transcripts for several different IGF-binding proteins (IGFBP-2, -3, -4, and -6) have been detected by RT-PCR procedures. In addition, transcripts for IGFBPs have been identified in RNA derived from cumulus cells, the ovary, the oviduct, the uterus, and the decidua. These findings suggest that the interactions of IGF ligands and receptors in preimplantation development might, indeed, be modulated by IGFBPs. Approaches to function of IGFs in preimplantation embryos have involved analysis of the stimulatory effects on metabolism and cell division when IGFs are added exogenously to embryos in culture in simple defined medium (for example, see Harvey and Kaye, 1991) or observations in the reduction in rate of development following interference with IGF expression (see Rappolee et al., 1992). In general, members of the insulin and IGF gene family of polypeptides have been shown to lead to an enhancement of development in vitro in both laboratory and domestic mammalian species. (C) 1993 Wiley-Liss, Inc.