UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology; Graduate School of Biomedical Sciences

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Document Type



Biochemical Phenomena, Metabolism, and Nutrition | Cellular and Molecular Physiology | Comparative and Evolutionary Physiology | Developmental Biology | Embryonic Structures | Genetics and Genomics


BACKGROUND: An organism's metabolic phenotype is primarily affected by its genotype, its lifestyle, and the nutritional composition of its food supply. In addition, it is now clear from studies in many different species that ancestral environments can also modulate metabolism in at least one to two generations of offspring.

SCOPE OF REVIEW: We limit ourselves here to paternal effects in mammals, primarily focusing on studies performed in inbred rodent models. Although hundreds of studies link paternal diets and offspring metabolism, the mechanistic basis by which epigenetic information in sperm programs nutrient handling in the next generation remains mysterious. Our goal in this review is to provide a brief overview of paternal effect paradigms and the germline epigenome. We then pivot to exploring one key mystery in this literature: how do epigenetic changes in sperm, most of which are likely to act transiently in the early embryo, ultimately direct a long-lasting physiological response in offspring?

MAJOR CONCLUSIONS: Several potential mechanisms exist by which transient epigenetic modifications, such as small RNAs or methylation states erased shortly after fertilization, could be transferred to more durable heritable information. A detailed mechanistic understanding of this process will provide deep insights into early development, and could be of great relevance for human health and disease.


Epigenetics, Intergenerational, Paternal effects, Placenta, Sperm

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Copyright 2019. Published by Elsevier GmbH. This is an open access article under the CC BY-NC-ND license (

DOI of Published Version



Galan C, Krykbaeva M, Rando OJ. Early life lessons: The lasting effects of germline epigenetic information on organismal development. Mol Metab. 2020 Aug;38:100924. doi: 10.1016/j.molmet.2019.12.004. Epub 2019 Dec 27. PMID: 31974037; PMCID: PMC7300385. Link to article on publisher's site

Journal/Book/Conference Title

Molecular metabolism

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Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.