Paternal Diet Induces Transgenerational Epigenetic Inheritance of DNA Methylation Signatures and Phenotypes in Sheep Model

Overview

Journal PNAS Nexus

Specialty General Medicine

Date 2023 Jan 30

PMID 36713326

Authors

Camila U Braz

Todd Taylor

Hadjer Namous

Jessica Townsend

Thomas Crenshaw

Hasan Khatib

Affiliations

Soon will be listed here.

Abstract

Transgenerational epigenetic inheritance (TEI) requires transmission of environmentally induced epigenetic changes and associated phenotypes to subsequent generations without continued exposure to the environmental factor that originated the change. TEI is well-established in plants and ; however, occurrence in mammals is debated and poorly understood. Here, we examined whether paternal diet from weaning to puberty-induced changes in sperm DNA methylation that were transmitted to subsequent generations. Over 100 methylated cytosines, environmentally altered in the F0 generation, were inherited by the F1 and F2 generations. Furthermore, the F0 paternal diet was associated with growth and male fertility phenotypes in subsequent generations. Differentially methylated cytosines were correlated with gene expression. Our results demonstrate that some sperm methylation sites may escape DNA methylation erasure and are transmitted to subsequent generations despite the 2 waves of epigenetic programming: in primordial germ cells and in embryos after fertilization. These results advance our understanding of the complex relationships between nature and nurture.

Citing Articles

Stable Transmission of DNA Methylation Epimutations from Germlines to the Liver and Their Association with Fatty Liver Disease in Medaka.

Chakraborty S, Anand S, Wang X, Bhandari R Res Sq. 2025; .

PMID: 39989969 PMC: 11844629. DOI: 10.21203/rs.3.rs-6010210/v1.

Impact of paternal high energy diets on semen quality and embryo development in cattle.

Fontes P, Bromfield J, Pohler K, Lamb G Reprod Fertil. 2025; .

PMID: 39898513 PMC: 11850050. DOI: 10.1530/RAF-24-0082.

The epigenetic mechanisms of adaption to the hot and humid climate in Hu sheep (Ovis aries).

Ren H, Jiang J, Li J, Sun X, Chen C, Liu L Physiol Rep. 2024; 12(24):e16164.

PMID: 39725653 PMC: 11671241. DOI: 10.14814/phy2.16164.

Influence of sire plane of nutrition and targeted body weight gain on ewe lamb growth, glucose metabolism, and ovarian reserve.

Bochantin-Winders K, Slavick K, Jurgens I, Hurlbert J, Menezes A, Kirsch J J Anim Sci. 2024; 102.

PMID: 39367596 PMC: 11600961. DOI: 10.1093/jas/skae301.

Investigating the impact of paternal age, paternal heat stress, and estimation of non-genetic paternal variance on dairy cow phenotype.

Fouere C, Hoze C, Besnard F, Boussaha M, Boichard D, Sanchez M Genet Sel Evol. 2024; 56(1):46.

PMID: 38890567 PMC: 11184688. DOI: 10.1186/s12711-024-00918-2.

References

Schlesinger F, Smith A, Gingeras T, Hannon G, Hodges E . De novo DNA demethylation and noncoding transcription define active intergenic regulatory elements. Genome Res. 2013; 23(10):1601-14. PMC: 3787258. DOI: 10.1101/gr.157271.113. View

Mukasa-Mugerwa E, Ezaz Z . Relationship of testicular growth and size to age, body weight and onset of puberty in Menz ram lambs. Theriogenology. 1992; 38(5):979-88. DOI: 10.1016/0093-691x(92)90172-n. View

Rakyan V, Chong S, Champ M, Cuthbert P, Morgan H, Luu K . Transgenerational inheritance of epigenetic states at the murine Axin(Fu) allele occurs after maternal and paternal transmission. Proc Natl Acad Sci U S A. 2003; 100(5):2538-43. PMC: 151376. DOI: 10.1073/pnas.0436776100. View

Sadler-Riggleman I, Klukovich R, Nilsson E, Beck D, Xie Y, Yan W . Epigenetic transgenerational inheritance of testis pathology and Sertoli cell epimutations: generational origins of male infertility. Environ Epigenet. 2019; 5(3):dvz013. PMC: 6736068. DOI: 10.1093/eep/dvz013. View

Iwasaki Y, Siomi M, Siomi H . PIWI-Interacting RNA: Its Biogenesis and Functions. Annu Rev Biochem. 2015; 84:405-33. DOI: 10.1146/annurev-biochem-060614-034258. View

Nadeau J . The nature of evidence for and against epigenetic inheritance. Genome Biol. 2015; 16:137. PMC: 4499204. DOI: 10.1186/s13059-015-0709-y. View

Gross N, Taylor T, Crenshaw T, Khatib H . The Intergenerational Impacts of Paternal Diet on DNA Methylation and Offspring Phenotypes in Sheep. Front Genet. 2020; 11:597943. PMC: 7674940. DOI: 10.3389/fgene.2020.597943. View

Zhou Y, Connor E, Bickhart D, Li C, Baldwin R, Schroeder S . Comparative whole genome DNA methylation profiling of cattle sperm and somatic tissues reveals striking hypomethylated patterns in sperm. Gigascience. 2018; 7(5). PMC: 5928411. DOI: 10.1093/gigascience/giy039. View

Luo R, Bai C, Yang L, Zheng Z, Su G, Gao G . DNA methylation subpatterns at distinct regulatory regions in human early embryos. Open Biol. 2018; 8(10). PMC: 6223221. DOI: 10.1098/rsob.180131. View

10.

Grossniklaus U, Kelly W, Kelly B, Ferguson-Smith A, Pembrey M, Lindquist S . Transgenerational epigenetic inheritance: how important is it?. Nat Rev Genet. 2013; 14(3):228-35. PMC: 4066847. DOI: 10.1038/nrg3435. View

11.

Adelson D, Raison J, Edgar R . Characterization and distribution of retrotransposons and simple sequence repeats in the bovine genome. Proc Natl Acad Sci U S A. 2009; 106(31):12855-60. PMC: 2722308. DOI: 10.1073/pnas.0901282106. View

12.

Xu W, Xu M, Wang L, Zhou W, Xiang R, Shi Y . Integrative analysis of DNA methylation and gene expression identified cervical cancer-specific diagnostic biomarkers. Signal Transduct Target Ther. 2019; 4:55. PMC: 6908647. DOI: 10.1038/s41392-019-0081-6. View

13.

Blanco Rodriguez J, Camprubi Sanchez C . Epigenetic Transgenerational Inheritance. Adv Exp Med Biol. 2019; 1166:57-74. DOI: 10.1007/978-3-030-21664-1_4. View

14.

Ponomaryova A, Rykova E, Gervas P, Cherdyntseva N, Mamedov I, Azhikina T . Aberrant Methylation of LINE-1 Transposable Elements: A Search for Cancer Biomarkers. Cells. 2020; 9(9). PMC: 7563416. DOI: 10.3390/cells9092017. View

15.

Lorincz M, Dickerson D, Schmitt M, Groudine M . Intragenic DNA methylation alters chromatin structure and elongation efficiency in mammalian cells. Nat Struct Mol Biol. 2004; 11(11):1068-75. DOI: 10.1038/nsmb840. View

16.

Constantinof A, Boureau L, Moisiadis V, Kostaki A, Szyf M, Matthews S . Prenatal Glucocorticoid Exposure Results in Changes in Gene Transcription and DNA Methylation in the Female Juvenile Guinea Pig Hippocampus Across Three Generations. Sci Rep. 2019; 9(1):18211. PMC: 6890750. DOI: 10.1038/s41598-019-54456-9. View

17.

Patil V, Ward R, Hesson L . The evidence for functional non-CpG methylation in mammalian cells. Epigenetics. 2014; 9(6):823-8. PMC: 4065179. DOI: 10.4161/epi.28741. View

18.

Liu Y . Revisiting Darwin's thoughts on environmentally induced heritable changes. Sci Total Environ. 2020; 738:139540. DOI: 10.1016/j.scitotenv.2020.139540. View

19.

Gapp K, Jawaid A, Sarkies P, Bohacek J, Pelczar P, Prados J . Implication of sperm RNAs in transgenerational inheritance of the effects of early trauma in mice. Nat Neurosci. 2014; 17(5):667-9. PMC: 4333222. DOI: 10.1038/nn.3695. View

20.

Pheiffer C, Erasmus R, Kengne A, Matsha T . Differential DNA methylation of microRNAs within promoters, intergenic and intragenic regions of type 2 diabetic, pre-diabetic and non-diabetic individuals. Clin Biochem. 2015; 49(6):433-438. DOI: 10.1016/j.clinbiochem.2015.11.021. View