Skip to main content

Advertisement

SpringerLink
Log in

Maternal obesity and malnourishment exacerbate perinatal oxidative stress resulting in diabetogenic programming in F1 offspring

  • Original Article
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

The effect of in-utero environment on fetal health and survival is long-lasting, and this is known as the fetal origin hypothesis. The oxidative stress state during gestation could play a pivotal role in fetal programming and development of diseases such as diabetes. In this study, we investigated the effect of intra-uterine obesity and malnutrition on oxidative stress markers in pancreatic and peripheral tissues of F1 offspring both prenatally and postnatally. Furthermore, the effect of postnatal diet on oxidative stress profile was evaluated. The results indicated that intra-uterine obesity and malnourishment significantly increased oxidative stress in F1 offspring. Moreover, the programming effect of obesity was more pronounced and protracted than malnutrition. The obesity-induced programming of offspring tissues was independent of high-caloric environment that the offspring endured; however, high-caloric diet potentiated its effect. In addition, pancreas and liver were the most affected tissues by fetal reprogramming both prenatally and postnatally. In conclusion, maternal obesity and malnutrition-induced oxidative stress could predispose offspring to insulin resistance and diabetes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

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

References

  1. Barker DJ (1990) The fetal and infant origins of adult disease. BMJ 301:1111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Simmons RA (2012) Developmental origins of diabetes: the role of oxidative stress. Best Pract Res Clin Endocrinol Metab 26:701–708

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Peuchant E, Brun J-L, Rigalleau V, Dubourg L, Thomas M-J, Daniel J-Y et al (2004) Oxidative and antioxidative status in pregnant women with either gestational or type 1 diabetes. Clin Biochem 37:293–298

    Article  CAS  PubMed  Google Scholar 

  4. Hracsko Z, Orvos H, Novak Z, Pal A, Varga IS (2008) Evaluation of oxidative stress markers in neonates with intra-uterine growth retardation. Redox Rep 13:11–16

    Article  CAS  PubMed  Google Scholar 

  5. Arikan S, Konuko\uglu D, Ar\ikan Ç, Akçay T, Davas I (2001) Lipid peroxidation and antioxidant status in maternal and cord blood. Gynecol Obstet Invest 51:145–149

    Article  CAS  PubMed  Google Scholar 

  6. Betteridge DJ (2000) What is oxidative stress? Metab Clin Exp 49:3–8

    Article  CAS  PubMed  Google Scholar 

  7. Valko M, Leibfritz D, Moncol J, Cronin MTD, Mazur M, Telser J (2007) Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 39:44–84

    Article  CAS  PubMed  Google Scholar 

  8. Hashimoto K, Pinkas G, Evans L, Liu H, Al-Hasan Y, Thompson LP (2012) Protective effect of N-acetylcysteine on liver damage during chronic intrauterine hypoxia in fetal guinea pig. Reprod Sci 19:1001–1009

    Article  PubMed  PubMed Central  Google Scholar 

  9. Stangenberg S, Nguyen LT, Chen H, Al-Odat I, Killingsworth MC, Gosnell ME et al (2015) Oxidative stress, mitochondrial perturbations and fetal programming of renal disease induced by maternal smoking. Int J Biochem Cell Biol 64:81–90

    Article  CAS  PubMed  Google Scholar 

  10. Wang X, Li H, De Leo D, Guo W, Koshkin V, Fantus IG et al (2004) Gene and protein kinase expression profiling of reactive oxygen species-associated lipotoxicity in the pancreatic $\beta$-cell line MIN6. Diabetes 53:129–140

    Article  CAS  PubMed  Google Scholar 

  11. Organization WH others (2015) Obesity and overweight Fact sheet N 311. 2014. Ref Type: http://www.who.int/mediacentre/factsheets/fs311/en/

  12. Goran MI, Ball GDC, Cruz ML (2003) Obesity and risk of type 2 diabetes and cardiovascular disease in children and adolescents. J Clin Endocrinol Metab 88:1417–1427

    Article  CAS  PubMed  Google Scholar 

  13. Özcan U, Cao Q, Yilmaz E, Lee A-H, Iwakoshi NN, Özdelen E et al (2004) Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science 306:457–461

    Article  PubMed  Google Scholar 

  14. FAO, IFAD, WFP (2014) The State of Food Insecurity in the World 2014 strengthening the enabling environment for food security and nutrition. FAO, Rome, Italy

  15. Pandey KB, Rizvi SI (2010) Markers of oxidative stress in erythrocytes and plasma during aging in humans. Oxid Med Cell Longev 3:2–12

    Article  PubMed  PubMed Central  Google Scholar 

  16. Strange RC, Spiteri MA, Ramachandran S, Fryer AA (2001) Glutathione-S-transferase family of enzymes. Mutat Res 482:21–26

    Article  CAS  PubMed  Google Scholar 

  17. Zelko IN, Mariani TJ, Folz RJ (2002) Superoxide dismutase multigene family: a comparison of the CuZn-SOD (SOD1), Mn-SOD (SOD2), and EC-SOD (SOD3) gene structures, evolution, and expression. Free Radic Biol Med 33:337–349

    Article  CAS  PubMed  Google Scholar 

  18. Richter C (1995) Oxidative damage to mitochondrial DNA and its relationship to ageing. Int J Biochem Cell Biol 27:647–653

    Article  CAS  PubMed  Google Scholar 

  19. Armstrong D, Browne R (1994) The analysis of free radicals, lipid peroxides, antioxidant enzymes and compounds related to oxidative stress as applied to the clinical chemistry laboratory. Adv Exp Med Biol 366:43–58

  20. Trevisan M, Browne R, Ram M, Muti P, Freudenheim J, Carosella AM et al (2001) Correlates of markers of oxidative status in the general population. Am J Epidemiol 154:348–356

    Article  CAS  PubMed  Google Scholar 

  21. Ademuyiwa O, Odusoga OL, Adebawo OO, Ugbaja R (2007) Endogenous antioxidant defences in plasma and erythrocytes of pregnant women during different trimesters of pregnancy. Acta Obstet Gynecol Scand 86:1175–1182

    Article  PubMed  Google Scholar 

  22. Malti N, Merzouk H, Merzouk S, Loukidi B, Karaouzene N, Malti A et al (2014) Oxidative stress and maternal obesity: feto-placental unit interaction. Placenta 35:411–416

    Article  CAS  PubMed  Google Scholar 

  23. Franco MCP, Akamine EH, Rebouças N, Carvalho MHC, Tostes RCA, Nigro D et al (2007) Long-term effects of intrauterine malnutrition on vascular function in female offspring: implications of oxidative stress. Life Sci 80:709–715

    Article  CAS  PubMed  Google Scholar 

  24. Kamel MA, Helmy MH, Hanafi MY, Mahmoud SA, Elfetooh HA, Badr MS (2014) Maternal obesity and malnutrition in rats differentially affect glucose sensing in the muscles and adipose tissues in the offspring. Int J Biochem Res Rev 4:440–469

    Article  CAS  Google Scholar 

  25. Kamel MA (2012) Prenatal effects of different intra-uterine milieus on fetal glucose sensing mechanisms during gestation in rats. J Diabet Metab 3:181

  26. Amoli MM, Moosavizadeh R, Larijani B (2005) Optimizing conditions for rat pancreatic islets isolation. Cytotechnology 48:75–78

    Article  PubMed  PubMed Central  Google Scholar 

  27. Griffith OW (1980) Determination of glutathione and glutathione disulfide using glutathione reductase and 2-vinylpyridine. Anal Biochem 106:207–212

    Article  CAS  PubMed  Google Scholar 

  28. Smith IK, Vierheller TL, Thorne CA (1988) Assay of glutathione reductase in crude tissue homogenates using 5,5′-dithiobis(2-nitrobenzoic acid). Anal Biochem 175:408–413

    Article  CAS  PubMed  Google Scholar 

  29. Habig WH, Pabst MJ, Jakoby WB (1976) Glutathione S-transferase AA from rat liver. Arch Biochem Biophys 175:710–716

    Article  CAS  PubMed  Google Scholar 

  30. Flohé L, Günzler WA (1984) Assays of glutathione peroxidase. Methods Enzymol 105:114

    Article  PubMed  Google Scholar 

  31. Marklund S, Marklund G (1974) Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 47:469–474

    Article  CAS  PubMed  Google Scholar 

  32. Draper H, Hadley M (1989) Malondialdehyde determination as index of lipid peroxidation. Methods Enzymol 186:421–431

    Article  Google Scholar 

  33. Barker D (2004) The developmental origins of adult disease. J Am Coll Nutr 23:588S–595S

    Article  CAS  PubMed  Google Scholar 

  34. Woodall S, Johnston B, Breier B, Gluckman P (1996) Chronic maternal undernutrition in the rat leads to delayed postnatal growth and elevated blood pressure of offspring. Pediatr Res 40:438–443

    Article  CAS  PubMed  Google Scholar 

  35. Tonkiss J, Shumsky JS, Shultz PL, Almeida SS, Galler JR (1995) Prenatal cocaine but not prenatal malnutrition affects foster mother-pup interactions in rats. Neurotoxicol Teratol 17:601–608

    Article  CAS  PubMed  Google Scholar 

  36. Codoner-Franch P, Tavárez-Alonso S, Murria-Estal R, Tortajada-Girbes M, Simo-Jorda R, Alonso-Iglesias E (2012) Elevated advanced oxidation protein products (AOPPs) indicate metabolic risk in severely obese children. Nutr Metab Cardiovasc Dis 22:237–243

    Article  CAS  PubMed  Google Scholar 

  37. Jain A, Jadhav AA, Varma M (2013) Relation of oxidative stress, zinc and alkaline phosphatase in protein energy malnutrition. Arch Physiol Biochem 119:15–21

    Article  CAS  PubMed  Google Scholar 

  38. Farley D, Tejero ME, Comuzzie AG, Higgins PB, Cox L, Werner SL et al (2009) Feto-placental adaptations to maternal obesity in the baboon. Placenta 30:752–760

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Qanungo S, Mukherjea M (2000) Ontogenic profile of some antioxidants and lipid peroxidation in human placental and fetal tissues. Mol Cell Biochem 215:11–19

    Article  CAS  PubMed  Google Scholar 

  40. Lappas M, Mittion A, Permezel M (2010) In response to oxidative stress, the expression of inflammatory cytokines and antioxidant enzymes are impaired in placenta, but not adipose tissue, of women with gestational diabetes. J Endocrinol 204:75–84

    Article  CAS  PubMed  Google Scholar 

  41. Vanderlelie J, Gude N, Perkins AV (2008) Antioxidant gene expression in preeclamptic placentae: a preliminary investigation. Placenta 29:519–522

    Article  CAS  PubMed  Google Scholar 

  42. Cadet J, Wagner JR (2013) DNA base damage by reactive oxygen species, oxidizing agents, and UV radiation. Cold Spring Harb Perspect Biol 5:a012559

    Article  PubMed  PubMed Central  Google Scholar 

  43. Grankvist K, Marklund SL, Taljedal I-B (1981) CuZn-superoxide dismutase, Mn-superoxide dismutase, catalase and glutathione peroxidase in pancreatic islets and other tissues in the mouse. Biochem J 199:393–398

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Reusens B, Theys N, Dumortier O, Goosse K, Remacle C (2011) Maternal malnutrition programs the endocrine pancreas in progeny. Am J Clin Nutr 94:1824S–1829S

    Article  CAS  PubMed  Google Scholar 

  45. Alfaradhi MZ, Fernandez-Twinn DS, Martin-Gronert MS, Musial B, Fowden A, Ozanne SE (2014) Oxidative stress and altered lipid homeostasis in the programming of offspring fatty liver by maternal obesity. Am J Physiol Regul Integr Comp Physiol 307:R26–R34

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Cannon MV, Buchner DA, Hester J, Miller H, Sehayek E, Nadeau JH et al (2014) Maternal nutrition induces pervasive gene expression changes but no detectable DNA methylation differences in the liver of adult offspring. PLoS One 9:e90335

    Article  PubMed  PubMed Central  Google Scholar 

  47. Ruskovska T, Bernlohr DA (2013) Oxidative stress and protein carbonylation in adipose tissue: implications for insulin resistance and diabetes mellitus. J Proteomics 92:323–334

    Article  CAS  PubMed  Google Scholar 

  48. Yuzefovych LV, Musiyenko SI, Wilson GL, Rachek LI (2013) Mitochondrial DNA damage and dysfunction, and oxidative stress are associated with endoplasmic reticulum stress, protein degradation and apoptosis in high fat diet-induced insulin resistance mice. PLoS One 8(1):e54059

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Heerwagen MJ, Miller MR, Barbour LA, Friedman JE (2010) Maternal obesity and fetal metabolic programming: a fertile epigenetic soil. Am J Physiol-Regul Integr Comp Physiol 299:R711–R722

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

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

Author information

Author notes

    Authors and Affiliations

    1. Department of Biochemistry, Medical Research Institute, Alexandria University, Alexandria, Egypt

      M. I. Saad, M. M. Haiba, M. Y. Hanafi & M. A. Kamel

    2. The Ritchie Centre, Hudson Institute of Medical Research, Monash University, Melbourne, VIC, Australia

      M. I. Saad

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

      T. M. Abdelkhalek & M. M. Saleh

    4. Department of Molecular Medicine, University of Padova, Padua, Italy

      S. H. Tawfik

    Authors
    1. M. I. Saad
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. T. M. Abdelkhalek
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. M. M. Haiba
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. M. M. Saleh
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. M. Y. Hanafi
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. S. H. Tawfik
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. M. A. Kamel
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to M. I. Saad.

    Ethics declarations

    Conflict of interest

    The authors declare that they have no conflict of interest.

    Ethical statement

    The Institutional Animal Care and Use Committee at the Medical Research Institute—Alexandria University—Alexandria—Egypt, has approved the animal protocol.

    Informed consent

    The study did not involve participation of humans and formal consent is not required.

    Additional information

    M. I. Saad and T. M. Abdelkhalek have contributed equally to this work.

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Saad, M.I., Abdelkhalek, T.M., Haiba, M.M. et al. Maternal obesity and malnourishment exacerbate perinatal oxidative stress resulting in diabetogenic programming in F1 offspring. J Endocrinol Invest 39, 643–655 (2016). https://doi.org/10.1007/s40618-015-0413-5

    Download citation

    • Received:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s40618-015-0413-5

    Keywords

    Search

    Navigation