Paternal low protein diet programs preimplantation embryo gene expression, fetal growth and skeletal development in mice

Watkins, Adam J., Sirovica, Slobodan, Stokes, Ben, Isaacs, Mark, Addison, Owen and Martin, Richard A. (2017). Paternal low protein diet programs preimplantation embryo gene expression, fetal growth and skeletal development in mice. BBA : Molecular Basis of Disease, 1863 (6), pp. 1371-1381.

Abstract

Defining the mechanisms underlying the programming of early life growth is fundamental for improving adult health and wellbeing. While the association between maternal diet, offspring growth and adult disease risk is well-established, the effect of father's diet on offspring development are largely unknown. Therefore, we fed male mice an imbalanced low protein diet (LPD) to determine the impact on post-fertilisation development and fetal growth. We observed that in preimplantation embryos derived from LPD fed males, expression of multiple genes within the central metabolic AMPK pathway was reduced. In late gestation, paternal LPD programmed increased fetal weight, however, placental weight was reduced, resulting in an elevated fetal:placental weight ratio. Analysis of gene expression patterns revealed increased levels of transporters for calcium, amino acids and glucose within LPD placentas. Furthermore, placental expression of the epigenetic regulators Dnmt1 and Dnmt3L were increased also, coinciding with altered patterns of maternal and paternal imprinted genes. More strikingly, we observed fetal skeletal development was perturbed in response to paternal LPD. Here, while offspring of LPD fed males possessed larger skeletons, their bones comprised lower volumes of high mineral density in combination with reduced maturity of bone apatite. These data offer new insight in the underlying programming mechanisms linking poor paternal diet at the time of conception with the development and growth of his offspring.

Publication DOI: https://doi.org/10.1016/j.bbadis.2017.02.009
Divisions: Life & Health Sciences > Biosciences
Engineering & Applied Sciences > Chemical engineering & applied chemistry
Engineering & Applied Sciences > Electrical, electronic & power engineering
Engineering & Applied Sciences > Polymer and advanced materials research group
Engineering & Applied Sciences
Additional Information: © 2017, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/
Uncontrolled Keywords: blastocyst metabolism,bone health,developmental programming,placental function,paternal diet,fetal growth,Molecular Medicine,Molecular Biology
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Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
Published Date: 2017-06-01
Authors: Watkins, Adam J.
Sirovica, Slobodan
Stokes, Ben
Isaacs, Mark
Addison, Owen
Martin, Richard A. ( 0000-0002-6013-2334)

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