Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Brief Communication
  • Published:

Genetics and Epigenetics

Sex-specific programming effects of parental obesity in pre-implantation embryonic development

International Journal of Obesity volume 44, pages 1185–1190 (2020)Cite this article

Subjects

Abstract

Background

Obesity is a global rising problem with epidemiological dimension. Obese parents can have programming effects on their offspring leading to obesity and associated diseases in later life. This constitutes a vicious circle. Epidemiological data and studies in rodents demonstrated differential programming effects in male and female offspring, but the timing of their developmental origin is not known.

Methods

This study investigated if sex-specific programming effects of parental obesity can already be detected in the pre-implantation period. Diet-induced obese male or female mice were mated with normal-weight partners and blastocysts were recovered.

Results

Gene expression profiling revealed sex-specific responses of the blastocyst transcriptome to maternal and paternal obesity. The changes in the transcriptome of male blastocysts were more pronounced than those of female blastocysts, with a stronger impact of paternal than of maternal obesity. The sperm of obese mice revealed an increased abundance of several miRNAs compared with lean mice.

Conclusions

Our study indicates that sex-specific programming effects of parental obesity already start in the pre-implantation period and reveals specific alterations of the sperm miRNA profile as mechanistic link to programming effects of paternal obesity.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2

References

  1. Fleming TP, Watkins AJ, Velazquez MA, Mathers JC, Prentice AM, Stephenson J, et al. Origins of lifetime health around the time of conception: causes and consequences. Lancet. 2018;391:1842–52.

    Article  Google Scholar 

  2. Huypens P, Sass S, Wu M, Dyckhoff D, Tschop M, Theis F, et al. Epigenetic germline inheritance of diet-induced obesity and insulin resistance. Nat Genet. 2016;48:497–9.

    Article  CAS  Google Scholar 

  3. Sun C, Denisenko O, Sheth B, Cox A, Lucas ES, Smyth NR, et al. Epigenetic regulation of histone modifications and Gata6 gene expression induced by maternal diet in mouse embryoid bodies in a model of developmental programming. BMC Dev Biol. 2015;15:3.

    Article  Google Scholar 

  4. Wang L, Zhang J, Duan J, Gao X, Zhu W, Lu X, et al. Programming and inheritance of parental DNA methylomes in mammals. Cell. 2014;157:979–91.

    Article  CAS  Google Scholar 

  5. Kawano M, Kawaji H, Grandjean V, Kiani J, Rassoulzadegan M. Novel small noncoding RNAs in mouse spermatozoa, zygotes and early embryos. PLoS ONE. 2012;7:e44542.

    Article  CAS  Google Scholar 

  6. Morgan HD, Santos F, Green K, Dean W, Reik W. Epigenetic reprogramming in mammals. Hum Mol Genet. 2005;14:R47–58.

    Article  CAS  Google Scholar 

  7. Lecoutre S, Deracinois B, Laborie C, Eberle D, Guinez C, Panchenko PE, et al. Depot- and sex-specific effects of maternal obesity in offspring’s adipose tissue. J Endocrinol. 2016;230:39–53.

    Article  CAS  Google Scholar 

  8. Sun B, Purcell RH, Terrillion CE, Yan J, Moran TH, Tamashiro KL. Maternal high-fat diet during gestation or suckling differentially affects offspring leptin sensitivity and obesity. Diabetes. 2012;61:2833–41.

    Article  CAS  Google Scholar 

  9. Ornellas F, Mello VS, Mandarim-de-Lacerda CA, Aguila MB. Sexual dimorphism in fat distribution and metabolic profile in mice offspring from diet-induced obese mothers. Life Sci. 2013;93:454–63.

    Article  CAS  Google Scholar 

  10. Masuyama H, Hiramatsu Y. Additive effects of maternal high fat diet during lactation on mouse offspring. PLoS ONE. 2014;9:e92805.

    Article  Google Scholar 

  11. Gallou-Kabani C, Gabory A, Tost J, Karimi M, Mayeur S, Lesage J, et al. Sex- and diet-specific changes of imprinted gene expression and DNA methylation in mouse placenta under a high-fat diet. PLoS ONE. 2010;5:e14398.

    Article  CAS  Google Scholar 

  12. Dahlhoff M, Pfister S, Blutke A, Rozman J, Klingenspor M, Deutsch MJ, et al. Peri-conceptional obesogenic exposure induces sex-specific programming of disease susceptibilities in adult mouse offspring. Biochim Biophys Acta. 2014;1842:304–17.

    Article  CAS  Google Scholar 

  13. Gapp K, Jawaid A, Sarkies P, Bohacek J, Pelczar P, Prados J, et al. Implication of sperm RNAs in transgenerational inheritance of the effects of early trauma in mice. Nat Neurosci. 2014;17:667–9.

    Article  CAS  Google Scholar 

  14. Fullston T, Ohlsson Teague EM, Palmer NO, DeBlasio MJ, Mitchell M, Corbett M, et al. Paternal obesity initiates metabolic disturbances in two generations of mice with incomplete penetrance to the F2 generation and alters the transcriptional profile of testis and sperm microRNA content. Faseb J. 2013;27:4226–43.

    Article  CAS  Google Scholar 

  15. Zhang Y, Shi J, Rassoulzadegan M, Tuorto F, Chen Q. Sperm RNA code programmes the metabolic health of offspring. Nat Rev Endocrinol. 2019;15:489–98.

    Article  Google Scholar 

  16. Goldstein JM, Holsen L, Huang G, Hammond BD, James-Todd T, Cherkerzian S, et al. Prenatal stress-immune programming of sex differences in comorbidity of depression and obesity/metabolic syndrome. Dialogues Clin Neurosci. 2016;18:425–36.

    PubMed  PubMed Central  Google Scholar 

  17. Mingrone G, Manco M, Mora ME, Guidone C, Iaconelli A, Gniuli D, et al. Influence of maternal obesity on insulin sensitivity and secretion in offspring. Diabetes Care. 2008;31:1872–6.

    Article  Google Scholar 

  18. Donkin I, Versteyhe S, Ingerslev LR, Qian K, Mechta M, Nordkap L, et al. Obesity and bariatric surgery drive epigenetic variation of spermatozoa in humans. Cell Metab. 2016;23:369–78.

    Article  CAS  Google Scholar 

  19. Cropley JE, Eaton SA, Aiken A, Young PE, Giannoulatou E, Ho JWK, et al. Male-lineage transmission of an acquired metabolic phenotype induced by grand-paternal obesity. Mol Metab. 2016;5:699–708.

    Article  CAS  Google Scholar 

  20. Grandjean V, Fourre S, De Abreu DA, Derieppe MA, Remy JJ, Rassoulzadegan M. RNA-mediated paternal heredity of diet-induced obesity and metabolic disorders. Scientific Rep. 2015;5:18193.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors would like to thank Sylvia Mallok and Andrea Klanner (microarray analysis and quantitative RT-PCR) for their expert assistance, and Dr. Ingrid Renner-Müller and Petra Renner for excellent animal care.

Funding

This study was supported in part by the German Center for Diabetes Research (DZD).

Author information

Authors and Affiliations

  1. Institute of Molecular Animal Breeding and Biotechnology, Gene Center, Ludwig-Maximilians-Universität München, Feodor-Lynen-Strasse 25, 81377, Munich, Germany

    Kathrin Hedegger, Eckhard Wolf & Maik Dahlhoff

  2. Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, Ludwig-Maximilians-Universität München, Feodor-Lynen-Strasse 25, 81377, Munich, Germany

    Julia Philippou-Massier, Stefan Krebs, Helmut Blum & Eckhard Wolf

  3. Department of Biochemistry, Gene Center, Ludwig-Maximilians-Universität München, Feodor-Lynen-Strasse 25, 81377, Munich, Germany

    Stefan Kunzelmann & Klaus Förstemann

  4. Research Center, Dr. von Hauner Children’s Hospital, Ludwig-Maximilians-Universität München, Lindwurmstrasse 4, 80337, Munich, Germany

    Martina Gimpfl, Adelbert A. Roscher & Regina Ensenauer

  5. Experimental Pediatrics and Metabolism, Department of General Pediatrics, Neonatology and Pediatric Cardiology, University Children’s Hospital, Heinrich Heine University Düsseldorf, Moorenstrasse 5, 40225, Düsseldorf, Germany

    Regina Ensenauer

  6. German Center for Diabetes Research (DZD), Helmholtz Zentrum München, Ingolstädter Landstr. 1, 85764, Neuherberg, Germany

    Eckhard Wolf

Authors
  1. Kathrin Hedegger
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Julia Philippou-Massier
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Stefan Krebs
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Helmut Blum
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Stefan Kunzelmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Klaus Förstemann
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Martina Gimpfl
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Adelbert A. Roscher
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Regina Ensenauer
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Eckhard Wolf
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Maik Dahlhoff
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Maik Dahlhoff.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hedegger, K., Philippou-Massier, J., Krebs, S. et al. Sex-specific programming effects of parental obesity in pre-implantation embryonic development. Int J Obes 44, 1185–1190 (2020). https://doi.org/10.1038/s41366-019-0494-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41366-019-0494-x

This article is cited by

Search

Advanced search

Quick links