Developmental origins of health and disease (DOHaD) and paternal origins of health and disease (POHaD). Multigenerational inheritance

This review addresses the concept of ontogenetic origin of health and disease (DOHaD) and the new concept of paternal origin of health and disease (POHaD). These concepts are based on scientific evidence that environmental factors impacting mother or father can play a role in reprogramming the health of their off springs throughout their life span. Moreover, the changes that have arisen can be transmitted through generations via diverse epigenetic mechanisms. Terms, such as epigenetics (a kind of “driver” for these concepts), epigenetic inheritance (including Intergenerational Inheritance – from generation to the next generation and Transgenerational Inheritance – through generations), epigenetic changes caused by the environment (Environmental Epigenetics) are discussed. Vulnerable periods towards epigenetic changes (Windows of Susceptibility) that occur in male germ cells responsible for epigenetic inheritance are considered. Epigenetic epidemiological studies in the field of reproductology are described; their advantages and disadvantages are discussed. These studies can serve as the basis for obtaining new knowledge about the causes of epigenetic variations in germ cells that occur in health and upon exposure to environmental factors as well as the inherited phenotypic outcomes.

1. Barker D.J. The origins of the developmental origins theory. J Intern Med. 2007;261(5):412–7. DOI: 10.1111/j.1365-2796.2007.01809.x.

2. Preston J.D., Reynolds L.J., Pearson K.J. Developmental origins of health span and life span: A mini-review. Gerontology. 2018;64(3):237–45. DOI: 10.1159/000485506.

3. Ho S.M., Cheong A., Adgent M.A. et al. Environmental factors, epigenetics, and developmental origin of reproductive disorders. Reprod Toxicol. 2017;68:85–104. DOI: 10.1016/j.reprotox.2016.07.011.

4. Soubry A., Hoyo C., Jirtle R.L., Murphy S.K. A paternal environmental legacy: evidence for epigenetic inheritance through the male germ line. BioEssays. 2014;36(4):359–71. DOI: 10.1002/bies.201300113.

5. Barker D.J. Developmental origins of adult health and disease. J Epidemiol Community Health. 2004;58(2):114–5. DOI: 10.1136/jech.58.2.114.

6. Barker D.J., Gluckman P.D., Godfrey K.M. et al. Fetal nutrition and cardiovascular disease in adult life. Lancet. 1993;341(8850):938–41. DOI: 10.1016/0140-6736(93)91224-a.

7. Hales C.N., Barker D.J. Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis. Diabetologia. 1992;35(7):595–601.

8. Wadhwa P.D., Buss C., Entringer S., Swanson J.M. Developmental origins of health and disease: brief history of the approach and current focus on epigenetic mechanisms. Semin Reprod Med. 2009;27(5):358–68. DOI: 10.1055/s-0029-1237424.

9. Rando O.J., Simmons R.A. I’m eating for two: parental dietary effects on offspring metabolism. Cell. 2015;161(1):93–105. DOI: 10.1016/j.cell.2015.02.021.

10. Soubry A. POHaD: why we should study future fathers. Environ Epigenet. 2018;4(2):dvy007. DOI: 10.1093/eep/dvy007.

11. Donkin I., Barres R. Sperm epigenetics and influence of environmental factors. Mol Metab. 2018;14:1–11. DOI: 10.1016/j.molmet.2018.02.006.

12. Watkins A.J., Dias I., Tsuro H. et al. Paternal diet programs offspring health through sperm- and seminal plasma-specific pathways in mice. Proc Natl Acad Sci USA. 2018;115(40):10064–9. DOI: 10.1073/pnas.1806333115.

13. Watson J.D., Baker T.A., Gann A. et al. Molecular biology of the gene. 7th ed. Cold Spring Harbor, New-York: Cold Spring Harbor Laboratory Press, 2014. 872 p.

14. Skinner M.K., Manikkam M., Guerrero-Bosagna C. Epigenetic transgenerational actions of environmental factors in disease etiology. Trends Endocrinol Metab. 2010;21(4):214–22. DOI: 10.1016/j.tem.2009.12.007.

15. Soubry A. Epigenetics as a driver of developmental origins of health and disease: did we forget the fathers? Bioessays. 2018;40(1):1700113. DOI: 10.1002/bies.201700113.

16. Nikitin A.I., Sergeev O.V., Suvorov A.N. The influence of harmful environmental factors on the reproductive, endocrine system and epigenome. [Vliyanie vrednyh faktorov sredy na reproduktivnuyu, endokrinnuyu sistemy i epigenom]. Moskva: Akvarel’, 2016. 348 s. (In Russ.).

17. Vanyushin B.F. Epigenetics today and tomorrow. Russian Journal of Genetics: Applied Research. 2014;4(3):168–88. DOI: 10.1134/S2079059714030083.

18. Cavalli G., Heard E. Advances in epigenetics link genetics to the environment and disease. Nature. 2019;571(7766):489–99. DOI: 10.1038/s41586-019-1411-0.

19. Nilsson E.E., Sadler-Riggleman I., Skinner M.K. Environmentally induced epigenetic transgenerational inheritance of disease. Environ Epigenet. 2018;4(2):dvy016. DOI: 10.1093/eep/dvy016.

20. Tuscher J.J., Day J.J. Multigenerational epigenetic inheritance: One step forward, two generations back. Neurobiol Dis. 2019;132:104591. DOI: 10.1016/j.nbd.2019.104591.

21. Skinner M.K. Environmental stress and epigenetic transgenerational inheritance. BMC Med. 2014;12:153. DOI: 10.1186/s12916-014-0153-y.

22. Wei Y., Schatten H., Sun Q.Y. Environmental epigenetic inheritance through gametes and implications for human reproduction. Hum Reprod Update. 2015;21(2):194–208. DOI: 10.1093/humupd/dmu061.

23. Tang W.W., Kobayashi T., Irie N. et al. Specification and epigenetic programming of the human germ line. Nat Rev Genet. 2016;17(10):585–600. DOI: 10.1038/nrg.2016.88.

24. Molaro A., Hodges E., Fang F. et al. Sperm methylation profiles reveal features of epigenetic inheritance and evolution in primates. Cell. 2011;146(6):1029–41. DOI: 10.1016/j.cell.2011.08.016.

25. Pilsner J.R., Parker M., Sergeyev O., Suvorov A. Spermatogenesis disruption by dioxins: Epigenetic reprograming and windows of susceptibility. Reprod Toxicol. 2017;69:221–9. DOI: 10.1016/j.reprotox.2017.03.002.

26. Wu H., Hauser R., Krawetz S.A., Pilsner J.R. Environmental susceptibility of the sperm epigenome during windows of male germ cell development. Curr Environ Health Rep. 2015;2(4):356–66. DOI: 10.1007/s40572-015-0067-7.

27. Mill J., Heijmans B.T. From promises to practical strategies in epigenetic epidemiology. Nat Rev Genet. 2013;14(8):585–94. DOI: 10.1038/nrg3405.

28. Michels K.B. Epigenetic epidemiology. Springer Netherlands, 2012. 448 p.

29. Messerlian C., Gaskins A.J. Epidemiologic approaches for studying assisted reproductive technologies: design, methods, analysis and interpretation. Curr Epidemiol Rep. 2017;4(2):124–32. DOI: 10.1007/s40471-017-0105-0.

30. Messerlian C., Williams P.L., Ford J.B. et al. The Environment and Reproductive Health (EARTH) Study: A Prospective Preconception Cohort. Hum Reprod Open. 2018;2018(2). pii: hoy001. DOI: 10.1093/hropen/hoy001.