Paternally induced transgenerational inheritance of susceptibility to diabetes in mammals
Open accessAbstract
Significance: Increasing evidence suggests that certain acquired traits can be transmitted to the next generation. However, controversy over the inheritance of acquired traits remains, as the exact molecular and mechanistic basis for these observations remains largely unclear. In this study, using a nongenetic prediabetes mouse model, we have shown that environmentally induced epigenetic alterations in sperm can be inherited to the next generation. Paternal prediabetic conditions affect epigenetic marks in offspring and can be inherited for several generations. This finding provides a molecular basis for the inheritance of acquired traits and may have implications in explaining the prevalence of obesity, type 2 diabetes, and other chronic metabolic diseases.
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Wei et al. found that streptozotocin-induced prediabetes in male mice affected DNA methylation patterns in sperm as well as pancreatic islets of F1 and F2 offspring.
“Wei et al.8, for example, found that streptozotocin-induced prediabetes in male mice affected DNA methylation patterns in sperm as well as pancreatic islets of F1 and F2 offspring.”
From A critical view on transgenerational epigenetic inheritance in humans (2018) · cites this paper as [8]
Cites
A genome-wide association study identifies novel risk loci for type 2 diabetes
Sladek, R., Rocheleau, G., Rung, J., Dina, C., Shen, L., Serre, D., Boutin, P., Vincent, D., Belisle, A., Hadjadj, S., et al. (2007) · Nature · doi:10.1038/nature05616 · Cited by 2,993 · see citing works
A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants
Scott, L. J., Mohlke, K. L., Bonnycastle, L. L., Willer, C. J., Li, Y., Duren, W. L., Erdos, M. R., Stringham, H. M., Chines, P. S., Jackson, A. U., et al. (2007) · Science · doi:10.1126/science.1142382 · Cited by 2,753 · see citing works
Transposable elements: targets for early nutritional effects on epigenetic gene regulation
Waterland, R. A., & Jirtle, R. L. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.15.5293-5300.2003 · Cited by 2,019 · cited 1× · see citing works
“As cytosine methylation is a widespread DNA modification that carries heritable information between generations (6, 18), we therefore turned to genome-wide studies to search for differentially methylated loci between control and prediabetic offspring.”
BackgroundGenotype score in addition to common risk factors for prediction of type 2 diabetes
Meigs, J. B., Shrader, P., Sullivan, L. M., McAteer, J. B., Fox, C. S., Dupuis, J., Manning, A. K., Florez, J. C., Wilson, P. W. F., D'Agostino, R. B., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0804742 · Cited by 759 · cited 1× · see citing works
“Although some alleles have been identified to be associated with impaired fasting blood glucose or impaired glucose tolerance (13–15), the majority (>95%) of the patients with impaired fasting blood glucose or impaired glucose tolerance is unrelated to genetic background but is environmentally induced or contributed b…”
BackgroundTransgenerational Inheritance of an Acquired Small RNA-Based Antiviral Response in C. elegans
Rechavi, O., Minevich, G., & Hobert, O. (2011) · Cell · doi:10.1016/j.cell.2011.10.042 · Cited by 351 · see citing works
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MAFLD: a consensus-driven proposed nomenclature for metabolic associated fatty liver disease
Eslam, M., Sanyal, A. J., George, J., Sanyal, A., Neuschwander-Tetri, B., Tiribelli, C., Kleiner, D. E., Brunt, E., Bugianesi, E., Yki-Järvinen, H., et al. (2020) · Gastroenterology · doi:10.1053/j.gastro.2019.11.312 · Cited by 3,286 · see citing works
Sperm tsRNAs contribute to intergenerational inheritance of an acquired metabolic disorder
Chen, Q., Yan, M., Cao, Z., Li, X., Zhang, Y., Shi, J., Feng, G.-H., Peng, H., Zhang, X., Zhang, Y., et al. (2016) · Science · doi:10.1126/science.aad7977 · Cited by 1,470 · see citing works
Early Developmental Conditioning of Later Health and Disease: Physiology or Pathophysiology?
Hanson, M. A., & Gluckman, P. D. (2014) · Physiological Reviews · doi:10.1152/physrev.00029.2013 · Cited by 1,188 · see citing works
Epigenetic inheritance of acquired traits through sperm RNAs and sperm RNA modifications
Chen, Q., Yan, W., & Duan, E. (2016) · Nature Reviews Genetics · doi:10.1038/nrg.2016.106 · Cited by 576 · see citing works
Intergenerational and transgenerational epigenetic inheritance in animals
Perez, M. F., & Lehner, B. (2019) · Nature Cell Biology · doi:10.1038/s41556-018-0242-9 · Cited by 528 · see citing works
Disruption of histone methylation in developing sperm impairs offspring health transgenerationally
Siklenka, K., Erkek, S., Godmann, M., Lambrot, R., McGraw, S., Lafleur, C., Cohen, T., Xia, J., Suderman, M., Hallett, M., et al. (2015) · Science · doi:10.1126/science.aab2006 · Cited by 521 · see citing works
The impact of cellular metabolism on chromatin dynamics and epigenetics
Reid, M. A., Dai, Z., & Locasale, J. W. (2017) · Nature Cell Biology · doi:10.1038/ncb3629 · Cited by 515 · see citing works
Zhang, Y., Zhang, X., Shi, J., Tuorto, F., Li, X., Liu, Y., Liebers, R., Zhang, L., Qu, Y., Qian, J., et al. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0087-2 · Cited by 468 · see citing works
“…non-DNA sequence-based hereditary information carriers could be chemical marks associated with DNA, i.e. DNA methylation and histone modifications 8–10 , as well as diffusible molecules such as small non-coding RNAs (sncRNAs) 1, 11 ; all have the potential to encode and store paternally acquired…”
Epigenetic germline inheritance of diet-induced obesity and insulin resistance
Huypens, P., Sass, S., Wu, M., Dyckhoff, D., Tschöp, M., Theis, F., Marschall, S., de Angelis, M. H., & Beckers, J. (2016) · Nature Genetics · doi:10.1038/ng.3527 · Cited by 366 · see citing works
A critical view on transgenerational epigenetic inheritance in humans
Horsthemke, B. (2018) · Nature Communications · doi:10.1038/s41467-018-05445-5 · Cited by 349 · see citing works
Molecular insights into transgenerational non-genetic inheritance of acquired behaviours
Bohacek, J., & Mansuy, I. M. (2015) · Nature Reviews Genetics · doi:10.1038/nrg3964 · Cited by 318 · see citing works
Pembrey, M., Saffery, R., Bygren, L. O., & Network in Epigenetic Epidemiology (2014) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2014-102577 · Cited by 325 · see citing works
Epigenetics in male reproduction: effect of paternal diet on sperm quality and offspring health
Schagdarsurengin, U., & Steger, K. (2016) · Nature Reviews Urology · doi:10.1038/nrurol.2016.157 · Cited by 222 · see citing works
The role of diet and exercise in the transgenerational epigenetic landscape of T2DM
Barrès, R., & Zierath, J. R. (2016) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2016.87 · Cited by 198 · see citing works
Metabolic Inputs into the Epigenome
Sharma, U., & Rando, O. J. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.02.003 · Cited by 167 · see citing works
A guide to designing germline-dependent epigenetic inheritance experiments in mammals
Bohacek, J., & Mansuy, I. M. (2017) · Nature Methods · doi:10.1038/nmeth.4181 · Cited by 80 · see citing works
DNA methylation in epigenetic inheritance of metabolic diseases through the male germ line
Illum, L. R. H., Bak, S. T., Lund, S., & Nielsen, A. L. (2018) · Journal of Molecular Endocrinology · doi:10.1530/jme-17-0189 · Cited by 51 · see citing works
Sarker, G., Berrens, R., von Arx, J., Pelczar, P., Reik, W., Wolfrum, C., & Peleg-Raibstein, D. (2018) · Translational Psychiatry · doi:10.1038/s41398-018-0243-2 · Cited by 45 · see citing works
Kaspi, A., Khurana, I., Ziemann, M., Connor, T., Spolding, B., Zimmet, P., Walder, K., & El‐Osta, A. (2018) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201800134 · Cited by 19 · see citing works
Guo, T., Hu, Z., Bao, L., Cao, Y., Chu, Z., Wang, M., Li, Y., & Luo, F. (2025) · Frontiers in Nutrition · doi:10.3389/fnut.2025.1680793 · Cited by 7 · see citing works
- Authors
- Wei, Y., Yang, C.-R., Wei, Y.-P., Zhao, Z.-A., Hou, Y., Schatten, H., & Sun, Q.-Y.
- Affiliations
- Chinese Academy of Sciences (CN)
- State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China;
- Department of Obstetrics and Gynecology, Changyi People’s Hospital, Weifang 261300, China; and
- University of Missouri (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2014-01-21
- Volume
- 111
- Issue
- 5
- Pages
- 1873-1878
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3918818
- OpenAlex
- W2073122969
- Cited by
- 423
- References
- 5
- Citations by year
- 2026: 7 · 2025: 22 · 2024: 21 · 2023: 29 · 2022: 41 · 2021: 29 · 2020: 37 · 2019: 40 · 2018: 54 · 2017: 47 · 2016: 35 · 2015: 40 · 2014: 20
- FWCI
- 19.42
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
- Keywords
- transgenerational epigenetic inheritance, type 2 diabetes risk, sperm DNA methylation, pancreatic islets, insulin resistance, impaired glucose tolerance, differentially methylated genes
- MeSH terms
- Animals, Blastocyst, Crosses, Genetic, Diabetes Mellitus, Fathers, Female, Insulin, Insulin Resistance, Islets of Langerhans, Male, Mammals, Prediabetic State, Spermatozoa, Streptozocin, Signal Transduction, Glucose Intolerance, DNA Methylation, Genetic Predisposition to Disease, Inheritance Patterns, Epigenesis, Genetic
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