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Who's your daddy?: paternal inheritance of metabolic disease risk

Isganaitis, Elvira; Suehiro, Harumi; Cardona, Connie

Current Opinion in Endocrinology, Diabetes and Obesity: February 2017 - Volume 24 - Issue 1 - p 47–55
doi: 10.1097/MED.0000000000000307
GROWTH AND DEVELOPMENT: Edited by Lynne L. Levitsky
Editor's Choice

Purpose of review Although the importance of optimizing mothers’ health prior to conception and during pregnancy is now well accepted, recent data also implicate health and nutritional status of fathers as contributors to chronic disease risk in their progeny. This brief review will highlight recent epidemiological and experimental studies linking paternal overnutrition, undernutrition, and other forms of stress, to metabolic disease in the offspring.

Recent findings The past 2 years have brought tremendous insights into the mechanisms by which paternal exposures can contribute to disease susceptibility in the next generation. Recent data, both from humans and experimental models, demonstrate that paternal obesity and undernutrition result in epigenetic reprogramming of male germ cells, notably altered DNA methylation, histone retention, and expression of small noncoding RNAs and transfer RNA fragments. Novel mechanisms have also been identified, such as epididymal transport vesicles, seminal fluid hormones and metabolites, and a unique seminal fluid microbiome.

Summary Paternal nutritional and other perturbations are linked to risk of metabolic disease and obesity in offspring. Germ cell-dependent mechanisms have recently been linked to these intergenerational effects. Nongenetic, paternal inheritance of chronic disease has important implications for public health, and may provide novel opportunities for multigenerational disease prevention.

Research Division, Joslin Diabetes Center, Boston, Massachusetts, USA

Correspondence to Elvira Isganaitis, MD, MPH, Research Division, Joslin Diabetes Center, One Joslin Place Room 607, Boston, MA 02215, USA. Tel: +1 617 309 4554; fax: +1 617 309 2451; e-mail:

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