akusherstvoObstetrics, Gynecology and ReproductionАкушерство, Гинекология и Репродукция2313-73472500-3194IRBIS LLC10.17749/2313-7347.2019.13.4.326-336akusherstvo-601Research ArticleREVIEW ARTICLEНАУЧНЫЙ ОБЗОРDevelopmental origins of health and disease (DOHaD) and paternal origins of health and disease (POHaD). Multigenerational inheritanceКонцепции первопричин здоровья и болезней на ранних периодах развития (DOHaD) и отцовских первопричин, передаваемых следующим поколениям (POHaD)https://orcid.org/0000-0002-5745-3348СергеевО. В.SergeyevO. V.

Сергеев Олег Владимирович – к.м.н., старший научный сотрудник, руководитель группы эпигенетической эпидемиологии

Россия, 119991 Москва, Ленинские горы, д. 1.

Scopus Author ID: 8708534100. Researcher ID: H-8854-2013.

Oleg V. Sergeyev – MD, PhD, Senior Researcher, Head of group of Epigenetic Epidemiology

Leninskie gory, Moscow 119234, Russia

Scopus Author ID: 8708534100. Researcher ID: H-8854-2013.

olegsergeyev1@yandex.ruНикитинА. И.NikitinA. I.

Никитин Анатолий Илларионович – д.м.н., профессор, научный директор

Россия, 197110 Санкт-Петербург, ул. Вязовая, д. 10, лит. А.

Scopus Author ID: 7202983989.

Anatoliy I. Nikitin – MD, PhD, Professor, Scientific Director.

10 Lit. A, Vyazovaya St., Saint-Petersburg 197110, Russia.

Scopus Author ID: 7202983989.

Научно-исследовательский институт физико-химической биологии имени А.Н. Белозерского, ФГБОУ ВО «Московский государственный университет имени М.В. Ломоносова»РоссияA.N. Belozersky Research Institute of Physico-Chemical Biology, Lomonosov Moscow State UniversityRussian FederationООО «Балтийский институт репродуктологии человека»РоссияBaltic Institute of Human ReproductionRussian Federation201916012020134326336Copyright © Sergeyev O.V., Nikitin A.I., 20202020Сергеев О.В., Никитин А.И.Sergeyev O.V., Nikitin A.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.gynecology.su/jour/article/view/601

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.

В обзоре рассматривается онтогенетическая концепция инициации здоровья и болезней (англ. Developmental Origins of Health and Disease, DOHaD) и новая концепция отцовских первопричин здоровья и болезней (англ. Paternal Origins of Health and Disease, POHaD), основанные на научных данных, говорящих о том, что воздействие факторов окружающей среды как на мать, так и на отца может играть роль в репрограммировании здоровья следующего поколения на протяжении всей жизни, а возникшие изменения могут быть переданы через поколения посредством сложных и разнообразных эпигенетических механизмов. Описаны такие термины, как эпигенетика, являющаяся своеобразным «драйвером» для данных концепций, эпигенетическое наследование (англ. Intergenerational Inheritance – от поколения к поколению и Transgenerational Inheritance – через поколения), эпигенетические изменения, вызываемые окружающей средой (англ. Environmental Epigenetics). Рассмотрены периоды уязвимости (англ. Windows of Susceptibility) для возникновения эпигенетических изменений в мужских половых клетках, ответственных за эпигенетическое наследование. Описаны эпигенетические эпидемиологические (англ. Epigenetic Epidemiology) исследования в области репродуктологии, оцениваются их достоинства и недостатки. Данные исследования могут служить основой для получения новых знаний о причинах эпигенетических вариаций в половых клетках, возникающих в норме и при воздействии факторов окружающей среды, и их фенотипических последствиях, передаваемых по наследству.

периоды уязвимостиполовые клеткиокружающая средаэпигенетическое наследованиеэпигенетическая эпидемиологияDOHaDPOHaDperiods of vulnerabilitygerm cellsenvironmentepigenetic inheritanceepigenetic epidemiologyDOHaDPOHaDReferencesBarker 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.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.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.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.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.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.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.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.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.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.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.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.Hales C.N., Barker D.J. Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis. Diabetologia. 1992;35(7):595–601.Hales C.N., Barker D.J. Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis. Diabetologia. 1992;35(7):595–601.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.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.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.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.Soubry A. POHaD: why we should study future fathers. Environ Epigenet. 2018;4(2):dvy007. DOI: 10.1093/eep/dvy007.Soubry A. POHaD: why we should study future fathers. Environ Epigenet. 2018;4(2):dvy007. DOI: 10.1093/eep/dvy007.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.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.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.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.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.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.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.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.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.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.Никитин А.И., Сергеев О.В., Суворов А.Н. Влияние вредных факторов среды на репродуктивную, эндокринную системы и эпигеном. М.: Акварель, 2016. 348 c.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.).Vanyushin B.F. Epigenetics today and tomorrow. Russian Journal of Genetics: Applied Research. 2014;4(3):168–88. DOI: 10.1134/S2079059714030083.Vanyushin B.F. Epigenetics today and tomorrow. Russian Journal of Genetics: Applied Research. 2014;4(3):168–88. DOI: 10.1134/S2079059714030083.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.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.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.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.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.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.Skinner M.K. Environmental stress and epigenetic transgenerational inheritance. BMC Med. 2014;12:153. DOI: 10.1186/s12916-014-0153-y.Skinner M.K. Environmental stress and epigenetic transgenerational inheritance. BMC Med. 2014;12:153. DOI: 10.1186/s12916-014-0153-y.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.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.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.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.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.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.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.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.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.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.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.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.Michels K.B. Epigenetic epidemiology. Springer Netherlands, 2012. 448 p.Michels K.B. Epigenetic epidemiology. Springer Netherlands, 2012. 448 p.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.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.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.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.

The authors declare that there are no conflicts of interest present.