3 minute lightning oral presentation (and poster) ESA-SRB 2023 in conjunction with ENSA

The role of insulin-like growth factor binding protein-3 in mouse embryo implantation (#205)

Kate B Carey 1 , Monique H Rayhanna 1 , Michael B Morris 1 , Margot L Day 1
  1. School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, New South Wales, Australia

Preimplantation embryo development in vitro is poorer and results in decreased implantation rates compared to those developed in vivo. A contributing factor to these problems in vitro may be the lack of maternally derived growth factors, such as insulin-like growth factor binding protein-3 (IGFBP3) (1-2). Exogenous IGFBP3 improves mouse preimplantation embryo development by increasing cell division rate between the 2-cell and 8-cell stage, blastocyst formation and hatching (3-4). IGFBP3 can act via insulin-like growth factor-independent mechanisms, such as via the sphingosine-1-phosphate (S1P) signalling pathway (5) and this may occur in mouse embryos to promote preimplantation embryo development (3-4) and implantation. In this study, embryos were exposed to IGFBP3 during preimplantation development and to IGFBP3 and/or S1P at the embryonic-maternal interface during implantation. Two measures of implantation were assessed; attachment where blastocysts were co-cultured with Ishikawa cells, a receptive human endometrial adenocarcinoma cell line for 48 h, and invasion where blastocysts were transferred to coverslips for outgrowth for 96 h. Exposure to IGFBP3 during preimplantation embryo development improved blastocyst attachment but had no effect on outgrowth. Exposure to IGFBP3 only during the implantation process reduced blastocyst outgrowth area and had no effect on attachment. Exposure to S1P during implantation had no effect on blastocyst attachment or outgrowth and did not prevent the reduced outgrowth caused by IGFBP3. In conclusion, adding IGFBP3, only during implantation, is not beneficial but it improves attachment when added to embryo culture medium during preimplantation development, and thus should be considered as a media component to improve the outcomes of assisted reproductive technologies.

  1. Hahnel, A & Schultz, GA 1994, ‘Insulin-Like Growth Factor Binding Proteins are Transcribed by Preimplantation Mouse Embryos’, Endocrinology, vol. 134, no. 4, pp. 1956-9, DOI 10.1210/endo.134.4.7511095.
  2. Lai, YM, Wang, HS, Lee, CL, Lee, JD, Huang, HY, Chang, FH, Lee, JF & Soong, YK 1996, ‘Insulin-like growth factor-binding proteins produced by Vero cells, human oviductal cells and human endometrial cells, and the role of insulin-like growth factor-binding protein-3 in mouse embryo co-culture systems’, Human Reproduction, vol. 11, no. 6, pp. 1281-6, DOI 10.1093/oxfordjournals.humrep.a019372.
  3. Green, CJ, Span, M, Rayhanna, MH, Perera, M & Day, ML 2022, ‘Insulin-like Growth Factor Binding Protein 3 Increases Mouse Preimplantation Embryo Cleavage Rate by Activation of IGF1R and EGFR Independent of IGF1 Signalling’, Cells, vol. 11, no. 23, pp. e3762, DOI 10.3390/cells11233762.
  4. Rayhanna, M 2019, ‘The role of sphingosine-1-phosphate in insulin-like growth factor binding protein-3 mediated improvement in mouse preimplantation embryo development’ Honours Thesis, The University of Sydney.
  5. Martin, JL, Lin, MZ, Mcgowan, EM & Baxter, RC 2009, ‘Potentiation of Growth Factor Signaling by Insulin-like Growth Factor-binding Protein-3 in Breast Epithelial Cells Requires Sphingosine Kinase Activity’, The Journal of Biological Chemistry, vol. 284, no. 38, pp. 25542-52, DOI 10.1074/jbc.M109.007120.