Routine addition of human insulin-like growth factor-I ligand could benefit clinical in-vitro fertilization culture.
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.
Lighten
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Division of Paediatrics, Obstetrics & Gynaecology, Imperial College School of Medicine, Hammersmith Hospital, London, UK.
Moore
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Winston
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Hardy
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D001755:Blastocyst / Q000737:chemistry / Q000502:physiology; D001826:Body Fluids / Q000737:chemistry; D003470:Culture Media; D003593:Cytoplasm / Q000737:chemistry; D005314:Embryonic and Fetal Development; D004848:Epithelium / Q000737:chemistry; D005187:Fallopian Tubes / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D005307:Fertilization in Vitro; D006801:Humans; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D017526:Receptor, IGF Type 1 / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014599:Uterus / Q000378:metabolism
D003470:Culture Media; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1