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Insulin and branched-chain amino acid depletion during mouse preimplantation embryo culture programmes body weight gain and raised blood pressure during early postnatal life

Insulin and branched-chain amino acid depletion during mouse preimplantation embryo culture programmes body weight gain and raised blood pressure during early postnatal life
Insulin and branched-chain amino acid depletion during mouse preimplantation embryo culture programmes body weight gain and raised blood pressure during early postnatal life
Mouse maternal low protein diet exclusively during preimplantation development (Emb-LPD) is sufficient to programme altered growth and cardiovascular dysfunction in offspring. Here, we use an in vitro model comprising preimplantation culture in medium depleted in insulin and branched-chain amino acids (BCAA), two proposed embryo programming inductive factors from Emb-LPD studies, to examine the consequences for blastocyst organisation and, after embryo transfer (ET), postnatal disease origin. Two-cell embryos were cultured to blastocyst stage in defined KSOM medium supplemented with four combinations of insulin and BCAA concentrations. Control medium contained serum insulin and uterine luminal fluid amino acid concentrations (including BCAA) found in control mothers from the maternal diet model (N-insulin + N-bcaa). Experimental medium (three groups) contained 50% reduction in insulin and/or BCAA (L-insulin + N-bcaa, N-insulin + L-bcaa, and L-insulin + N-bcaa). Lineage-specific cell numbers of resultant blastocysts were not affected by treatment. Following ET, a combined depletion of insulin and BCAA during embryo culture induced a non sex-specific increase in birth weight and weight gain during early postnatal life. Furthermore, male offspring displayed relative hypertension and female offspring reduced heart/body weight, both characteristics of Emb-LPD offspring. Combined depletion of metabolites also resulted in a strong positive correlation between body weight and glucose metabolism that was absent in the control group. Our results support the notion that composition of preimplantation culture medium can programme development and associate with disease origin affecting postnatal growth and cardiovascular phenotypes and implicate two important nutritional mediators in the inductive mechanism. Our data also have implications for human assisted reproductive treatment (ART) practice.
0925-4439
590-600
Velazquez, Miguel A.
3b67a037-eed3-4268-92f8-7a4b58473472
Sheth, Bhavwanti
2ca6ed58-a992-47b7-b3a5-3c5df82aada7
Smith, Stephanie J.
b93e230c-cc90-42f5-ae47-19354008d2fa
Eckert, Judith J.
729bfa49-7053-458d-8e84-3e70e4d98e57
Osmond, Clive
2677bf85-494f-4a78-adf8-580e1b8acb81
Fleming, Tom P.
2abf761a-e5a1-4fa7-a2c8-12e32d5d4c03
Velazquez, Miguel A.
3b67a037-eed3-4268-92f8-7a4b58473472
Sheth, Bhavwanti
2ca6ed58-a992-47b7-b3a5-3c5df82aada7
Smith, Stephanie J.
b93e230c-cc90-42f5-ae47-19354008d2fa
Eckert, Judith J.
729bfa49-7053-458d-8e84-3e70e4d98e57
Osmond, Clive
2677bf85-494f-4a78-adf8-580e1b8acb81
Fleming, Tom P.
2abf761a-e5a1-4fa7-a2c8-12e32d5d4c03

Velazquez, Miguel A., Sheth, Bhavwanti, Smith, Stephanie J., Eckert, Judith J., Osmond, Clive and Fleming, Tom P. (2018) Insulin and branched-chain amino acid depletion during mouse preimplantation embryo culture programmes body weight gain and raised blood pressure during early postnatal life. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1864 (2), 590-600. (doi:10.1016/j.bbadis.2017.11.020).

Record type: Article

Abstract

Mouse maternal low protein diet exclusively during preimplantation development (Emb-LPD) is sufficient to programme altered growth and cardiovascular dysfunction in offspring. Here, we use an in vitro model comprising preimplantation culture in medium depleted in insulin and branched-chain amino acids (BCAA), two proposed embryo programming inductive factors from Emb-LPD studies, to examine the consequences for blastocyst organisation and, after embryo transfer (ET), postnatal disease origin. Two-cell embryos were cultured to blastocyst stage in defined KSOM medium supplemented with four combinations of insulin and BCAA concentrations. Control medium contained serum insulin and uterine luminal fluid amino acid concentrations (including BCAA) found in control mothers from the maternal diet model (N-insulin + N-bcaa). Experimental medium (three groups) contained 50% reduction in insulin and/or BCAA (L-insulin + N-bcaa, N-insulin + L-bcaa, and L-insulin + N-bcaa). Lineage-specific cell numbers of resultant blastocysts were not affected by treatment. Following ET, a combined depletion of insulin and BCAA during embryo culture induced a non sex-specific increase in birth weight and weight gain during early postnatal life. Furthermore, male offspring displayed relative hypertension and female offspring reduced heart/body weight, both characteristics of Emb-LPD offspring. Combined depletion of metabolites also resulted in a strong positive correlation between body weight and glucose metabolism that was absent in the control group. Our results support the notion that composition of preimplantation culture medium can programme development and associate with disease origin affecting postnatal growth and cardiovascular phenotypes and implicate two important nutritional mediators in the inductive mechanism. Our data also have implications for human assisted reproductive treatment (ART) practice.

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Accepted/In Press date: 26 November 2017
e-pub ahead of print date: 28 November 2017
Published date: 1 February 2018

Identifiers

Local EPrints ID: 416265
URI: https://eprints.soton.ac.uk/id/eprint/416265
ISSN: 0925-4439
PURE UUID: 20f3724b-4c85-4d2f-8395-3f849559f9f8
ORCID for Clive Osmond: ORCID iD orcid.org/0000-0002-9054-4655

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Date deposited: 11 Dec 2017 17:30
Last modified: 19 Nov 2019 01:58

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Contributors

Author: Miguel A. Velazquez
Author: Bhavwanti Sheth
Author: Stephanie J. Smith
Author: Clive Osmond ORCID iD
Author: Tom P. Fleming

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