Paternal Nongenetic Intergenerational Transmission of Metabolic Disease Risk

  • Lei Su
  • Mary Elizabeth PattiEmail author
Pathogenesis of Type 2 Diabetes and Insulin Resistance (M-E Patti, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Pathogenesis of Type 2 Diabetes and Insulin Resistance


Purpose of Review

Paternal metabolic disease before conception and during spermatogenesis can adversely impact the metabolic health of offspring in later life. Here, we review the current understanding of sperm epigenetic markers as contributors to intergenerational transmission of disease risk in both human and animal studies, and review potential intervention strategies.

Recent Findings

Epidemiological studies suggest an increased risk of adverse outcomes in the offspring of fathers with obesity, diabetes, advanced age, smoking, and ancestral exposures. Potential molecular mechanisms contributing to intergenerational disease risk include genetics (DNA sequence) as well as epigenetic factors in the sperm, such as DNA methylation, chromatin and histone modification, and coding and noncoding RNAs. Potential strategies to interrupt intergenerational transmission of disease risk include increased physical activity, weight loss, bariatric surgery, cold exposure, and improved glycemic control prior to conception.


Many studies suggest environmental factors experienced by fathers can program disease risk in the next generation via sperm cell–mediated transmission. Better understanding the mechanisms through which paternal metabolism influences sperm cells will help to design better intervention strategies. Future research will focus on the molecular signals that mediate the impact of paternal factors on sperm epigenetic signals and also how these affect offspring embryonic development and disease risk during adult life.


Paternal obesity Epigenetics Intergenerational inheritance Sperm 



Mary Elizabeth Patti reports grants from NIH (DK106193, HD091974, DK036836).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Research DivisionJoslin Diabetes Center and Harvard Medical SchoolBostonUSA
  2. 2.The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina

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