Why is epigenetic inheritance important

Genetics Home Reference has merged with MedlinePlus. Learn more. The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.

What is epigenetics? From Genetics Home Reference. Topics in the How Genes Work chapter What are proteins and what do they do? How do genes direct the production of proteins? Can genes be turned on and off in cells? How do cells divide? How do genes control the growth and division of cells? Observing the behavioral outcomes of the various levels of manipulation could allow one to identify the point at which the lack of a certain transcriptional product has relevant consequences and thus when and where its activity is necessary.

Figure 5. From in vitro fertilization IVF to fostering. Once its role in fetal programming has been established, investigating its possible play in transgenerational epigenetic inheritance processes might be easier. See the text for more details. Conditional models are preferred when defining the weight of a specific effector in a specific place and time e.

In contrast, developmental models should allow one to observe the final, complex outcome of a certain alteration of a gene such as polymorphisms and genes that encode epigenetic elements in a more complex, systemic manner.

The latter approach is not conducive to gaining a precise understanding of mechanisms but still has ecological value that cannot be ignored. Another noteworthy issue concerns whether to use IVF or natural breeding, followed by embryo extraction and implantation.

IVF requires superovulation and the use of an artificial culture, which could alter the programing of gametes Bohacek and Mansuy, The use of natural breeding, conversely, fails to control for the effects of the manipulation of male and female reproductive fluids Bohacek and Mansuy, , warranting further comparison with offspring that result from natural breeding. These considerations are pivotal to correctly interpret data, despite the manipulation of a factor and the breeding procedure e.

Moreover, the proposed model is only theoretical and does not impose its complete application, although it would likely produce the strongest evidence possible, whatever results emerge. Once the activity of a certain effector has been described, a more specific molecular analysis can be conducted to link the steps of the underlying mechanism of the specific process of epigenetic inheritance.

In this review article, we have introduced the concept of epigenetics, defining its spatial and temporal properties, allowing us to distinguish between types of epigenetics: a direct form of epigenetics DE and two forms of indirect epigenetics—within WIE and across AIE.

We have organized the main body of epigenetic evidence according to these three categories and focused on the latter AIE , referring to it as a more rapid means of transmitting information across generations—compared with genetic inheritance—that guides human evolution in a Lamarckian i. We have thus defined epigenetic inheritance in terms of AIE and illustrated the putative molecular mechanisms of this phenomenon.

Finally, we have discussed the main methodological matters regarding the study of epigenetic inheritance and have suggested strategies to solve some of the most compelling technical and theoretical problems that plague this field. There is no doubt that translational research could benefit from this scientific effort. Epigenetic inheritance, when maladaptive, can have a silent, unseen, but dramatic impact on health, perpetrating detrimental adaptations across generations.

The peculiar nature of epigenetics could allow us to intervene at various levels synchronously, thus applying more effective synergistic activity against complex diseases, which have not been able to be properly understood or approached until now—particularly on the molecular level. We could prevent malicious epigenetic forms of inheritance, evaluating the quality of germ cells in high-risk cases and eventually administering pharmacological treatments that target specific epigenetic mechanisms, as recently suggested by Pang et al.

Germline and somatic cells have been studied as putative targets for genetic therapy to prevent the evolution and transmission of several human pathologies Baltimore et al. Thus, there is no reason why a similar therapeutic approach should be overlooked for epigenetic abnormalities that affect an individual at early age and even during fetal development.

To strengthen the therapeutic power of the environment, paradoxically, we must understand the specific mechanisms that are altered by epigenetic adaptations following certain experiences. Notably, several peripheral biomarkers have been defined to assess placental dysfunction and other general abnormalities during pregnancy Maccani et al. Conversely, it would be helpful to monitor the observable, phenomenological patterns e. Attaining this ideal therapeutic power will require new studies on AIE—particularly on the gap between two generations.

Although we have detailed how epigenetic factors can lead to many pathologies, we must be reminded that they are usually crucial in all of the adaptive processes that ensure the survival of the individual and species van Otterdijk and Michels, For this reason, the decision to interfere with their activity should be strongly supported by a profound understanding of the specific case in question and applied with great caution.

IL conceived the general theoretical framework, collected most of the bibliography, wrote the first draft of the article and designed and drew the figures. Both authors developed, refined and carefully reviewed the final version of the article.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

We wish to thank Dr. Al-Gubory, K. Environmental pollutants and lifestyle factors induce oxidative stress and poor prenatal development. Online 29, 17— Amaral, P. Non-coding RNAs in homeostasis, disease and stress responses: an evolutionary perspective.

Genomics 12, — Ambeskovic, M. Transgenerational effects of early environmental insults on aging and disease incidence. Andolina, D. Effects of lack of microRNA on the neural circuitry underlying the stress response and anxiety. Neuropharmacology , — Neuropsychopharmacology 38, — Anway, M. Epigenetic transgenerational actions of endocrine disruptors and male fertility. Science , — Arai, J.

Transgenerational rescue of a genetic defect in long-term potentiation and memory formation by juvenile enrichment. Avissar-Whiting, M. Bisphenol A exposure leads to specific microRNA alterations in placental cells. Azzi, A. Circadian behavior is light-reprogrammed by plastic DNA methylation. Babenko, O. Epigenetic programming of neurodegenerative diseases by an adverse environment.

Brain Res. Bakusic, J. Stress, burnout and depression: a systematic review on DNA methylation mechanisms. Baltimore, D. A prudent path forward for genomic engineering and germline gene modification. Science , 36— Barrientos, R. Brain-derived neurotrophic factor mRNA downregulation produced by social isolation is blocked by intrahippocampal interleukin-1 receptor antagonist. Neuroscience , — Baudry, A. MiR targets the serotonin transporter: a new facet for adaptive responses to antidepressants.

Belzeaux, R. Responder and nonresponder patients exhibit different peripheral transcriptional signatures during major depressive episode. Psychiatry 2:e Bennett-Baker, P. Age-associated activation of epigenetically repressed genes in the mouse. Genetics , — PubMed Abstract Google Scholar. Blahna, M. Smad-mediated regulation of microRNA biosynthesis. FEBS Lett. Bohacek, J. Molecular insights into transgenerational non-genetic inheritance of acquired behavior.

Braun, K. Paternal influences on offspring development: behavioural and epigenetic pathways. Bygren, L. Acta Biotheor. Byrnes, J. Adolescent opioid exposure in female rats: transgenerational effects on morphine analgesia and anxiety-like behavior in adult offspring. Cabib, S. The mesoaccumbens dopamine in coping with stress. Cardoso, M. DNA methyltransferase is actively retained in the cytoplasm during early development. Cell Biol. Cassidy, S. Prader-Willi and Angelman syndromes: sister imprinted disorders.

Chen, E. The epigenetic effects of antidepressant treatment on human prefrontal cortex BDNF expression. Chen, J.

Maternal deprivation in rats is associated with corticotrophinreleasing hormone CRH promoter hypomethylation and enhances CRH transcriptional responses to stress in adulthood. Chen, T. Structure and function of eukaryotic DNA methyltransferases. Chen, S. Correlation between the level of microRNA expression in peripheral blood mononuclear cells and symptomatology in patients with generalized anxiety disorder.

Psychiatry 69, — Chen, Q. Sperm tsRNAs contribute to intergenerational inheritance of an acquired metabolic disorder. Christensen, B. Epigenomics in environmental health. Cohen, J. Conradt, E. Epigenetics 8, — Conti, C. A brief review on epigenetic aspects involved in depression.

Cooper, G. Cooper and R. Hausman Sunderland: Sinauer Associates, Inc. Google Scholar. Crews, D. Epigenetics and its implications for behavioral neuroendocrinology.

Epigenetic transgenerational inheritance of altered stress responses. U S A , — Crick, F. Hildebrandt and P. Igarashi — Dawkins, R.

The Selfish Gene. Di Segni, M. Unstable maternal environment affects stress response in adult mice in a genotype-dependent manner. Cortex 26, — Dietz, D. Paternal transmission of stress induced pathologies. Psychiatry 70, — Domschke, K. Psychiatry 46, — Dorrington, S.

Perinatal maternal life events and psychotic experiences in children at twelve years in a birth cohort study. Dunn, G. Maternal high-fat diet promotes body length increases and insulin insensitivity in second-generation mice. Endocrinology , — Sex-specificity in transgenerational epigenetic programming. Elfving, B. Inverse correlation of brain and blood BDNF levels in a genetic rat model of depression.

Ender, C. Cell 32, — Faa, G. Fetal programming of neuropsychiatric disorders. C Embryo Today , — Fine, R. Prenatal stress and inhibitory neuron systems: implications for neuropsychiatric disorders. Psychiatry 19, — Finegersh, A. Paternal alcohol exposure reduces alcohol drinking and increases behavioral sensitivity to alcohol selectively in male offspring.

PLoS One 9:e Francis, D. Nongenomic transmission across generations of maternal behavior and stress responses in the rat. Franklin, T. Influence of early stress on social abilities and serotonergic functions across generations in mice. PLoS One 6:e Epigenetic transmission of the impact of early stress across generations.

Psychiatry 68, — Fraser, R. Epigenetic reprogramming of the zygote in mice and men: on your marks, get set, go!. Reproduction , R—R Galler, J. Home-orienting behavior in rat pups: the effect of 2 and 3 generations of rehabilitation following intergenerational malnutrition. Gapp, K. Early life epigenetic programming and transmission of stress-induced traits in mammals. How and when can environmental factors influence traits and their transgenerational inheritance?

Bioessays 36, — Godfrey, K. Epigenetic mechanisms and the mismatch concept of the developmental origins of health and disease. Gottlieb, G. Probabilistic epigenesis. Gu, Y. Differential miRNA expression profiles between the first and third trimester human placentas.

Govorko, D. Male germline transmits fetal alcohol adverse effect on hypothalamic proopiomelanocortin gene across generations. Psychiatry 72, — Haramati, S. MicroRNA as repressors of stress-induced anxiety: the case of amygdalar miR Haussecker, D. RNA 16, — He, N. Parental life events cause behavioral difference among offspring: adult pre-gestational restraint stress reduces anxiety across generations.

Heijmans, B. Persistent epigenetic differences associated with prenatal exposure to famine in humans. Hollins, S.

Houri-Zeevi, L. A matter of time: small RNAs regulate the duration of epigenetic inheritance. Trends Genet. Hu, M. Maternal testosterone exposure increases anxiety-like behavior and impacts the limbic system in the offspring.

Hunter, D. Programming the brain: common outcomes and gaps in knowledge from animal studies of IUGR. Hyslop, L. Towards clinical application of pronuclear transfer to prevent mitochondrial DNA disease.

Nature , — Issler, O. Determining the role of microRNAs in psychiatric disorders. MicroRNA is essential for chronic stress resiliency, antidepressant efficacy, and intact serotonergic activity. Neuron 83, — Jawahar, M. Epigenetic alterations following early postnatal stress: a review on novel aetiological mechanisms of common psychiatric disorders.

Epigenetics Johnson, T. Blumberg, J. Freeman and S. Jones, P. Functions of DNA methylation: islands, starts sites, gene bodies and beyond. Jung, M. Aging and DNA methylation. BMC Biol. Kaati, G. Karege, F. Low brain-derived neurotrophic factor BDNF levels in serum of depressed patients probably results from lowered platelet BDNF release unrelated to platelet reactivity. Psychiatry 57, — Kellermann, N. Epigenetic transmission of holocaust trauma: can nightmares be inherited?

Psychiatry Relat. Kember, R. Maternal separation is associated with strain-specific responses to stress and epigenetic alterations to Nr3c1, Avp, and Nr4a1 in mouse. Brain Behav. Khundakar, A. Biphasic change in BDNF expression following antidepressant drug treatment explained by differential transcript regulation.

Kolshus, E. When less is more—microRNAs and psychiatric disorders. Acta Psychiatr. Koob, G. Neurocircutry of addiction. Neuropsychopharmacology 35, — Kovalchuk, I. Transgenerational epigenetic inheritance in animals. Launay, J. Raphe-mediated signals control the hippocampal response to SRI antidepressants via miR Psychiatry 1:e Leshem, M. Transgenerational effects of infantile adversity and enrichment in male and female rats. Liu, G. A meta-analysis of the genomic and transcriptomic composition of complex life.

Cell Cycle 12, — Lumey, L. Prenatal famine and adult health. Public Health 32, — Luteijn, M. Lyall, K. Maternal lifestyle and environmental risk factors for autism spectrum disorders. Ma, J. MicroRNA activity is suppressed in mouse oocytes. Maccani, M. Maternal cigarette smoking during pregnancy is associated with downregulation of miR, miR and miRa in the placenta. Epigenetics 5, — Placental miRNA expression profiles are associated with measures of infant neurobehavioral outcomes.

Maccari, S. Early-life experiences and the development of adult diseases with a focus on mental illness: the human Birth theory. Maffioletti, E. Geneticists analyzed years worth of harvest records from a small town in Sweden. They saw a connection between food availability large or small harvests in one generation and the incidence of diabetes and heart disease in later generations.

The amount of food a grandfather had to eat between the ages of 9 and 12 was especially important. This is when boys go through the slow growth period SGP , and form the cells that will give rise to sperm. As these cells form, the epigenome is copied along with the DNA.

Since the building blocks for the epigenome come from the food a boy eats, his diet could impact how faithfully the epigenome is copied. Proving epigenetic inheritance is not always straightforward. To provide a watertight case for epigenetic inheritance, researchers must:. Researchers face the added challenge that epigenetic changes are transient by nature. That is, the epigenome changes more rapidly than the relatively fixed DNA code.

An epigenetic change that was triggered by environmental conditions may be reversed when environmental conditions change again. Three generations at once are exposed to the same environmental conditions diet, toxins, hormones, etc. In order to provide a convincing case for epigenetic inheritance, an epigenetic change must be observed in the 4th generation. Epigenetic inheritance adds another dimension to the modern picture of evolution.

The genome changes slowly, through the processes of random mutation and natural selection. It takes many generations for a genetic trait to become common in a population. The epigenome, on the other hand, can change rapidly in response to signals from the environment. And epigenetic changes can happen in many individuals at once. Through epigenetic inheritance, some of the experiences of the parents may pass to future generations. At the same time, the epigenome remains flexible as environmental conditions continue to change.

Epigenetic inheritance may allow an organism to continually adjust its gene expression to fit its environment - without changing its DNA code. Fish, E. Epigenetic programming of stress responses through variations in maternal care. Annals of the New York Academy of Science subscription required. Youngson, N. Transgenerational epigenetic effects. Annual Reviews in Genomics and Human Genetics 9: subscription required. Kaati, G. Transgenerational response to nutrition, early life circumstances and longevity.

European Journal of Human Genetics Chong, S. Epigenetic germline inheritance.