EXPRESSION OF IGF LIGAND AND RECEPTOR GENES DURING PREIMPLANTATION MAMMALIAN DEVELOPMENT

The temporal patterns of expression of genes encoding insulin-like gro wth factor (IGF) ligands and receptors during very early development h ave been investigated in several laboratories in several different mam malian species. Both reverse transcription-polymerase chain reaction ( RT-PCR) and immunocytochemical techniques have been used to identify t he time of appearance of gene transcripts or end-products. In preimpla ntation mouse embryos, IGF-II ligand and receptor gene activity is det ectable 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. Transc ripts 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 m ammalian species. In cow embryos, for example, transcripts for IGF-I a nd IGF-II ligands and receptors and insulin receptors have been detect ed at all stages of preimplantation development from mature oocyte to blastocyst (Watson et al., 1992). Attempts to quantitate transcript ab undance in these early embryos are in progress in our laboratory. In t he preimplantation mouse embryo, transcripts for several different IGF -binding proteins (IGFBP-2, -3, -4, and -6) have been detected by RT-P CR procedures. In addition, transcripts for IGFBPs have been identifie d in RNA derived from cumulus cells, the ovary, the oviduct, the uteru s, and the decidua. These findings suggest that the interactions of IG F ligands and receptors in preimplantation development might, indeed, be modulated by IGFBPs. Approaches to function of IGFs in preimplantat ion embryos have involved analysis of the stimulatory effects on metab olism and cell division when IGFs are added exogenously to embryos in culture in simple defined medium (for example, see Harvey and Kaye, 19 91) or observations in the reduction in rate of development following interference with IGF expression (see Rappolee et al., 1992). In gener al, members of the insulin and IGF gene family of polypeptides have be en shown to lead to an enhancement of development in vitro in both lab oratory and domestic mammalian species. (C) 1993 Wiley-Liss, Inc.