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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

Lookup NU author(s): Dr Miguel Velazquez



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


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.

Publication metadata

Author(s): Velazquez MA, Sheth B, Smith SJ, Eckert JJ, Osmond C, Fleming TP

Publication type: Article

Publication status: Published

Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease

Year: 2018

Volume: 1864

Issue: 2

Pages: 590-600

Print publication date: 01/02/2018

Online publication date: 28/11/2017

Acceptance date: 26/11/2017

Date deposited: 12/12/2017

ISSN (print): 0006-3002

ISSN (electronic): 1878-2434


DOI: 10.1016/j.bbadis.2017.11.020

PubMed id: 29196239


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Funder referenceFunder name
BBSRC BB/1001840/1