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Methylating micronutrient supplementation during pregnancy influences foetal hepatic gene expression and IGF signalling and increases foetal weight

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Abstract

Purpose

Maternal diet during pregnancy impacts foetal growth and development. In particular, dietary levels of methylating micronutrients (methionine, folate, choline, vitamins B6, and B12) interfere with the availability and allocation of methyl groups for methylation reactions, thereby influencing normal transcription. However, the currently recommended methylating micronutrient supplementation regimen is haphazard and arbitrary at best.

Methods

To investigate the effects of a methylating micronutrient-rich maternal diet, pregnant Pietrain sows were fed either a standard diet (CON) or a diet supplemented with methionine, folate, choline, B6, B12, and zinc (MET). Foetal liver and muscle (M. longissimus dorsi) tissues were collected at 35, 63, and 91 days post-conception. Transcriptional responses to diet were assessed in foetal liver. Altered insulin-like growth factor (IGF) signalling in transcriptome analyses prompted investigation of IGF-2 and insulin-like growth factor binding proteins (IGFBPs) levels in muscle and liver.

Results

Maternal diet enriched with methylating micronutrients was associated with increased foetal weight in late gestation. Hepatic transcriptional patterns also revealed differences in vitamin B6 and folate metabolism between the two diets, suggesting that supplementation was effective. Additionally, shifts in growth-supporting metabolic routes of the lipid and energy metabolism, including IGF signalling, and of cell cycle-related pathways were found to occur in liver tissue in supplemented individuals. Weight differences and modulated IGF pathways were also reflected in the muscle content of IGF-2 (increased in MET) and IGFBP-2 (decreased in MET).

Conclusions

Maternal dietary challenges provoke stage-dependent and tissue-specific transcriptomic modulations in the liver pointing to molecular routes contributing to the organismal adaptation. Subtle effects on late foetal growth are associated with changes in the IGF signalling mainly in skeletal muscle tissue that is less resilient to dietary stimuli than liver.

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Acknowledgments

The authors thank Hannelore Tychsen, Angela Garve, Annette Jugert, and Kerstin Jahnke for their excellent technical help.

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Authors and Affiliations

  1. Institute for Genome Biology, Leibniz Institute for Farm Animal Biology (FBN), Wilhelm-Stahl-Allee 2, 18196, Dummerstorf, Germany

    M. Oster, W. Nuchchanart, N. Trakooljul, E. Muráni, A. Hoeflich, S. Ponsuksili & K. Wimmers

  2. Department of Animal Nutrition, Martin-Luther-University Halle-Wittenberg, Theodor-Lieser-Str. 11, 06120, Halle (Saale), Germany

    A. Zeyner

  3. Ligandis GbR, Dorfstr. 14, 18276, Gülzow-Prüzen, Germany

    E. Wirthgen

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  1. M. Oster
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Correspondence to K. Wimmers.

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This work was partially funded by the 6th Research Framework Programme of the European Union as part of the SABRE project (cutting-edge genomics for sustainable animal breeding).

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The authors have declared that no competing interests exist. The manuscript does not contain clinical studies or patient data.

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Supplemental Table S1

Selected transcripts used for qPCR. Primers and correlation between microarray and qPCR are displayed (XLSX 293 kb)

Supplemental Table S2

Transcripts differing in mRNA levels between MET and CON liver samples (XLSX 89 kb)

Supplemental Table S3

Pathways altered between two ontogenetic stages within CON group in liver tissue (XLSX 14 kb)

Supplemental Table S4

Pathways altered between two ontogenetic stages within MET group in liver tissue (XLSX 14 kb)

Supplemental Table S5

IGFBP-1, IGFBP-2, IGFBP-3, and IGFBP-6 levels in foetal liver tissue (XLSX 13 kb)

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Oster, M., Nuchchanart, W., Trakooljul, N. et al. Methylating micronutrient supplementation during pregnancy influences foetal hepatic gene expression and IGF signalling and increases foetal weight. Eur J Nutr 55, 1717–1727 (2016). https://doi.org/10.1007/s00394-015-0990-2

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