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

Increased apoptosis in bovine blastocysts exposed to high levels of IGF1 is not associated with downregulation of the IGF1 receptor
Increased apoptosis in bovine blastocysts exposed to high levels of IGF1 is not associated with downregulation of the IGF1 receptor
The hypothesis that high concentrations of IGF1 can impair embryo development was investigated in a bovine in vitro model to reflect conditions in polycystic ovary syndrome (PCOS) patients. Embryos were either cultured in the absence or presence of a physiological (100? ng/ml) or supraphysiological (1000? ng/ml) IGF1 concentration. Cell allocation, apoptosis, transcript and protein expression of selected genes involved in apoptosis, glucose metabolism and the IGF system were analysed. Supraphysiological IGF1 concentration did not improve blastocyst formation over controls, but induced higher levels of apoptosis, decreased TP53 protein expression in the trophectoderm and increased the number of cells in the inner cell mass (ICM). The increase in ICM cells corresponded with an increase in IGF1 receptor (IGF1R) protein in the ICM. A small, but significant, percentage of blastocysts displayed a hypertrophic ICM, not observed in controls and virtually absent in embryos treated with physiological concentrations of IGF1. Physiological IGF1 concentrations increased total IGF1R protein expression and upregulated IGFBP3 transcripts leading to an increase in blastocyst formation with no effects on cell number or apoptosis. In conclusion, the results support the hypothesis of detrimental effects of supraphysiological IGF1 concentrations on early pregnancy. However, our results do not support the premise that increased apoptosis associated with high levels of IGF1 is mediated via downregulation of the IGF1R as previously found in preimplantation mouse embryos. This in vitro system with the bovine preimplantation embryo reflects critical features of fertility in PCOS patients and could thus serve as a useful model for in-depth mechanistic studies.
0022-4251
91-103
Velazquez, M.A.
706e7de5-8cdb-4f2b-b47d-128166bdbea4
Hermann, D.
4b0408c3-c3a8-4250-83d6-319bd03082e6
Kues, W.A.
38d7f0b8-75ed-415c-9844-03d9e2304e26
Niemann, H.
1fcd6d64-751c-4bd6-bbf7-901368d89478
Velazquez, M.A.
706e7de5-8cdb-4f2b-b47d-128166bdbea4
Hermann, D.
4b0408c3-c3a8-4250-83d6-319bd03082e6
Kues, W.A.
38d7f0b8-75ed-415c-9844-03d9e2304e26
Niemann, H.
1fcd6d64-751c-4bd6-bbf7-901368d89478

Velazquez, M.A., Hermann, D., Kues, W.A. and Niemann, H. (2011) Increased apoptosis in bovine blastocysts exposed to high levels of IGF1 is not associated with downregulation of the IGF1 receptor. Reproduction, 141 (1), 91-103. (doi:10.1530/REP-10-0336). (PMID:20926690)

Record type: Article

Abstract

The hypothesis that high concentrations of IGF1 can impair embryo development was investigated in a bovine in vitro model to reflect conditions in polycystic ovary syndrome (PCOS) patients. Embryos were either cultured in the absence or presence of a physiological (100? ng/ml) or supraphysiological (1000? ng/ml) IGF1 concentration. Cell allocation, apoptosis, transcript and protein expression of selected genes involved in apoptosis, glucose metabolism and the IGF system were analysed. Supraphysiological IGF1 concentration did not improve blastocyst formation over controls, but induced higher levels of apoptosis, decreased TP53 protein expression in the trophectoderm and increased the number of cells in the inner cell mass (ICM). The increase in ICM cells corresponded with an increase in IGF1 receptor (IGF1R) protein in the ICM. A small, but significant, percentage of blastocysts displayed a hypertrophic ICM, not observed in controls and virtually absent in embryos treated with physiological concentrations of IGF1. Physiological IGF1 concentrations increased total IGF1R protein expression and upregulated IGFBP3 transcripts leading to an increase in blastocyst formation with no effects on cell number or apoptosis. In conclusion, the results support the hypothesis of detrimental effects of supraphysiological IGF1 concentrations on early pregnancy. However, our results do not support the premise that increased apoptosis associated with high levels of IGF1 is mediated via downregulation of the IGF1R as previously found in preimplantation mouse embryos. This in vitro system with the bovine preimplantation embryo reflects critical features of fertility in PCOS patients and could thus serve as a useful model for in-depth mechanistic studies.

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Published date: January 2011
Organisations: Centre for Biological Sciences

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Local EPrints ID: 369453
URI: http://eprints.soton.ac.uk/id/eprint/369453
ISSN: 0022-4251
PURE UUID: a4bb17a4-1c1a-4663-a742-fa9705825a41

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Date deposited: 01 Oct 2014 15:48
Last modified: 15 Jul 2019 21:43

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