Routine addition of human insulin-like growth factor-I ligand could benefit clinical in-vitro fertilization culture

Abstract

Animal studies suggest that the insulin-like growth factors play an important role in preimplantation embryo development. Human preimplantation embryos express mRNA for insulin-like growth factor-I receptor (IGF-IR) but the ligand, insulin-like growth factor-I (IGF-I), is not expressed by the embryo until after implantation. We tested the hypothesis that IGF-I produced by the female reproductive tract may bind to these receptors, augmenting embryo survival, growth and development. Transcripts of mRNA for IGF1 were detected using reverse transcription-polymerase chain reaction in midcycle human Fallopian tube. Immunohistochemistry localized immunoreactive IGF-I to the cytoplasm of all the major structures of the Fallopian tube, with the most intense staining seen in the tubal epithelial lining. Maternally produced IGF-I was present in the fluid found in the human tube and uterus at concentrations of 8.0 and 10.9 nM respectively. Supplementation of culture medium with IGF-I increased the proportion of embryos developing to the blastocyst stage from 35% in controls to 60% in the presence of IGF-I. In addition the total number of cells in day 6 blastocysts was increased by 19% (64.44 versus 54.08% in control, not significant), due entirely to a statistically significant 59% increase (25 versus 15.75%, P = 0.020) in the number of cells in the inner cell mass. The effect of IGF-I was mediated through the IGF-I receptor. Immunocytochemistry using an alphaIR3 antibody confirmed the presence of IGF-I receptor in human blastocysts and the same antibody completely inhibited the stimulation of blastocyst formation by IGF-I. These data suggest that human preimplantation development is enhanced by maternal IGF-I. Mimicking this in-vivo paracrine relationship may improve clinical in-vitro embryo culture and IVF pregnancy rates.

Increased apoptosis in bovine blastocysts exposed to high levels of IGF1 is not associated with downregulation of the IGF1 receptor

“…This is consistent with previous studies that showed a selective increase of cells in the ICM in bovine blastocysts (Sirisathien et al 2003) and embryos from other species treated with IGF1, including humans (Lighten et al 1998), pigs (Kim et al 2005) and mice (Smith et al 1993). The localised cell proliferation seems to be related to activation of the MAPK pathway in the ICM by IGF1 (Navarrete Santos et al 2008).…”

“…Furthermore, the amino acid sequence of bovine IGF1 is identical to that of human IGF1 (Honegger & Humbel 1986, Francis et al 1988. In both the species, supplementation with physiological concentrations of human recombinant IGF1 can exert positive effects on in vitro preimplantation embryo development (Lighten et al 1998, Spanos et al 2000, Byrne et al 2002, Makarevich & Markkula 2002.…”

“…For instance, early embryos exposed to physiological concentrations of IGF1 (50-150 ng/ml) showed an increased number of cells in the resulting blastocysts in several mammalian species including mice (Lin et al 2003, Głabowski et al 2005, gerbil (Yoshida et al 2009), cattle (Byrne et al 2002, Makarevich & Markkula 2002, Sirisathien et al 2003, Jousan & Hansen 2007, buffaloes (Narula et al 1996), pigs (Kim et al 2005, rabbits (Herrler et al 1998) and humans (Lighten et al 1998). Physiological (100 ng/ ml) and supraphysiological (1000 ng/ml) concentrations of IGF1 increased the total cell number (TCN) in mice embryos in a dose-dependent manner (Głabowski et al 2005).…”

Unexpected detrimental effect of Insulin like growth factor-1 on bovine oocyte developmental competence under heat stress

“…In this study, proportion of M II oocytes were significantly (P<0.05) increased by IGF-1 supplementation at normal temperature condition (38.5°C) compared to the other groups. Stimulatory effect of IGF-1 on oocyte maturation and further embryo development is well established [14,20]. Also, it has been established that IGF-1 has a beneficial effect on oocyte nuclear maturation [21,22], whereas, oocyte expresses IGF-1 receptor [23].…”

“…Inhibition of apoptosis by means of using well known anti-apoptotic factors such as IGF-1 [9][10][11][12] may be a useful tool for decreasing the deterioration effects of heat stress on oocyte developmental competence. Insulin like grow factor-1 is a potent stimulator of oocyte maturation and subsequent embryonic development [13,14] and is a suppressor of apoptosis [13,15]. For the current experiments, it was hypothesized that the presence of IGF-1 during in vitro maturation (IVM) as an anti-apoptotic factor can improve bovine oocyte developmental competence under heat stress.…”