Haemoglobin expression in in vivo murine preimplantation embryos suggests a role in oxygen-regulated gene expression

M. Lim, H. M. Brown, K. L. Kind, J. Breen, M. R. Anastasi, L. J. Ritter, E. K. Tregoweth, D. T. Dinh, J. G. Thompson, K. R. Dunning

Research output: Contribution to journalArticle

Abstract

Haemoglobin expression is not restricted to erythroid cells. We investigated the gene expression of the haemoglobin subunits haemoglobin, alpha adult chain 1 (Hba-a1) and haemoglobin, beta (Hbb), 2,3-bisphosphoglycerate mutase (Bpgm) and the oxygen-regulated genes BCL2/adenovirus E1B interacting protein 3 (Bnip3), solute carrier family 2 (facilitated glucose transporter), member 1 (Slc2a1) and N-myc downstream regulated gene 1 (Ndrg1) in the murine preimplantation embryo, comparing in vivo to in vitro gene expression. Relatively high levels of Hba-a1 and Hbb were expressed in vivo from the 2-cell to blastocyst stage; in contrast, little or no expression occurred in vitro. We hypothesised that the presence of haemoglobin in vivo creates a low oxygen environment to induce oxygen-regulated gene expression, supported by high expression of Slc2a1 and Ndrg1 in in vivo relative to in vitro embryos. In addition, analysis of an in vitro-derived human embryo gene expression public dataset revealed low expression of haemoglobin subunit alpha (HBA) and HBB, and high expression of BPGM. To explore whether there was a developmental stage-specific effect of haemoglobin, we added exogenous haemoglobin either up to the 4-cell stage or throughout development to the blastocyst stage, but observed no difference in blastocyst rate or the inner cell mass to trophectoderm cell ratio. We conclude that haemoglobin in the in vivo preimplantation embryo raises an interesting premise of potential mechanisms for oxygen regulation, which may influence oxygen-regulated gene expression.

LanguageEnglish
Pages724-734
Number of pages11
JournalReproduction, Fertility and Development
Volume31
Issue number4
DOIs
Publication statusPublished - 1 Jan 2019

Keywords

  • IVF
  • gene regulation

ASJC Scopus subject areas

  • Biotechnology
  • Reproductive Medicine
  • Animal Science and Zoology
  • Molecular Biology
  • Genetics
  • Endocrinology
  • Developmental Biology

Cite this

Lim, M. ; Brown, H. M. ; Kind, K. L. ; Breen, J. ; Anastasi, M. R. ; Ritter, L. J. ; Tregoweth, E. K. ; Dinh, D. T. ; Thompson, J. G. ; Dunning, K. R. / Haemoglobin expression in in vivo murine preimplantation embryos suggests a role in oxygen-regulated gene expression. In: Reproduction, Fertility and Development. 2019 ; Vol. 31, No. 4. pp. 724-734.
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Haemoglobin expression in in vivo murine preimplantation embryos suggests a role in oxygen-regulated gene expression. / Lim, M.; Brown, H. M.; Kind, K. L.; Breen, J.; Anastasi, M. R.; Ritter, L. J.; Tregoweth, E. K.; Dinh, D. T.; Thompson, J. G.; Dunning, K. R.

In: Reproduction, Fertility and Development, Vol. 31, No. 4, 01.01.2019, p. 724-734.

Research output: Contribution to journalArticle

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T1 - Haemoglobin expression in in vivo murine preimplantation embryos suggests a role in oxygen-regulated gene expression

AU - Lim, M.

AU - Brown, H. M.

AU - Kind, K. L.

AU - Breen, J.

AU - Anastasi, M. R.

AU - Ritter, L. J.

AU - Tregoweth, E. K.

AU - Dinh, D. T.

AU - Thompson, J. G.

AU - Dunning, K. R.

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AB - Haemoglobin expression is not restricted to erythroid cells. We investigated the gene expression of the haemoglobin subunits haemoglobin, alpha adult chain 1 (Hba-a1) and haemoglobin, beta (Hbb), 2,3-bisphosphoglycerate mutase (Bpgm) and the oxygen-regulated genes BCL2/adenovirus E1B interacting protein 3 (Bnip3), solute carrier family 2 (facilitated glucose transporter), member 1 (Slc2a1) and N-myc downstream regulated gene 1 (Ndrg1) in the murine preimplantation embryo, comparing in vivo to in vitro gene expression. Relatively high levels of Hba-a1 and Hbb were expressed in vivo from the 2-cell to blastocyst stage; in contrast, little or no expression occurred in vitro. We hypothesised that the presence of haemoglobin in vivo creates a low oxygen environment to induce oxygen-regulated gene expression, supported by high expression of Slc2a1 and Ndrg1 in in vivo relative to in vitro embryos. In addition, analysis of an in vitro-derived human embryo gene expression public dataset revealed low expression of haemoglobin subunit alpha (HBA) and HBB, and high expression of BPGM. To explore whether there was a developmental stage-specific effect of haemoglobin, we added exogenous haemoglobin either up to the 4-cell stage or throughout development to the blastocyst stage, but observed no difference in blastocyst rate or the inner cell mass to trophectoderm cell ratio. We conclude that haemoglobin in the in vivo preimplantation embryo raises an interesting premise of potential mechanisms for oxygen regulation, which may influence oxygen-regulated gene expression.

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