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Diabetes-induced perturbations are subject to intergenerational transmission through maternal line

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Abstract

The hypothesis of fetal origins of adult disease states that early life events program the occurrence of significant adult diseases, including diabetes and obesity. Maternal diabetes is associated with general stress environment for developing fetus, and gestational diabetes is an independent risk factor for type 2 diabetes and metabolic syndrome in offspring. Intra-uterine fetal programming of fetal tissues exposes the offspring to increased risk of impaired glucose tolerance, type 2 diabetes, and cardiovascular disease. Here, we examined the transmission of maternal diabetes-induced fetal programming in second generation and compared maternal and paternal routes of intergenerational effects. We organized 40 Wistar rats into three groups, male offspring of diabetic mothers, female offspring of diabetic mothers, and offspring of control mothers. These groups were mated with normal healthy rats to assess the effect of grand-maternal diabetes on pregnancy outcome in F2 rats, as well as glucose-sensing parameters, insulin resistance, and glucose tolerance prenatally and postnatally. We found that F2 offspring of diabetic mothers had impaired glucose sensing, increased oxidative stress, insulin resistance, and impaired glucose tolerance, and these effects were more prominent in the F2 offspring of F1 female rats (F2-DF1F). We deduce that fetal programming of maternal diabetes is mostly transmitted through maternal line across two generations.

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Abbreviations

T2DM:

Type 2 diabetes mellitus

GSH:

Glutathione

GSSG:

Glutathione disulfide

GST:

Glutathione S transferase

GPx:

Glutathione peroxidase

GR:

Glutathione reductase

SOD:

Superoxide dismutase

ROS:

Reactive oxygen species

RNS:

Reactive nitrogen species

8-oxo-dG:

8-Oxo-7,8-dihydro-2′-deoxyguanosine

TBARS:

Thiobarbituric acid reactive substances

CRL:

Crown-rump length

CD:

Control diet

HCD:

High caloric diet

CF1/CD:

F1 offspring of control mother under CD

CF1/HCD:

F1 offspring of control mother under HCD

OF1/CD:

F1 offspring of obese mother under CD

OF1/HCD:

F1 offspring of obese mother under HCD

MF1/CD:

F1 offspring of malnourished mother under CD

MF1/HCD:

F1 offspring of malnourished mother under HCD

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Acknowledgments

This study is a part of project entitled “Intra-Uterine programming of adult diabetes: an experimental study” supported by the Science and Technology Development Fund (STDF)—Egypt.

Author’s contribution

Maher A. Kamel has conceived and designed the study, contributed to the analysis of the data, and to the writing and revising the manuscript. Mervat Y. Hanafi, Taha M. Abdelkhalek, Mohamed I. Saad, Maha M. Haiba and Moustafa M. Saleh have conducted most of the laboratory investigations and contributed to the writing and revising of the manuscript. All authors have read and approved the final manuscript.

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Authors and Affiliations

  1. Department of Biochemistry, Medical Research Institute, Alexandria University, 165 Elhorreya, Avenue, P.O. Box 21561, Alexandria, Egypt

    Mervat Y. Hanafi, Mohamed I. Saad, Maha M. Haiba & Maher A. Kamel

  2. Department of Human Genetics, Medical Research Institute, Alexandria University, Alexandria, Egypt

    Taha M. Abdelkhalek & Moustafa M. Saleh

  3. The Ritchie Centre, Hudson Institute of Medical Research, Monash University, Melbourne, Victoria, Australia

    Mohamed I. Saad

Authors
  1. Mervat Y. Hanafi
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  2. Taha M. Abdelkhalek
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  3. Mohamed I. Saad
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  4. Moustafa M. Saleh
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  6. Maher A. Kamel
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Corresponding author

Correspondence to Mohamed I. Saad.

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This article does not contain any studies with human subjects performed by any of the authors. The animal protocol was approved by the Institutional Animal Care and Use Committee at the Medical Research Institute—Alexandria University, Egypt.

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The authors declare that they have no conflict of interest.

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Hanafi, M.Y., Abdelkhalek, T.M., Saad, M.I. et al. Diabetes-induced perturbations are subject to intergenerational transmission through maternal line. J Physiol Biochem 72, 315–326 (2016). https://doi.org/10.1007/s13105-016-0483-7

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  • DOI: https://doi.org/10.1007/s13105-016-0483-7

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