Exploring the Interconnected Mechanisms of Transgenerational Epigenetic Inheritance
DOI:
https://doi.org/10.47611/jsrhs.v13i1.6459Keywords:
Epigenetics, Inheritance, Intrauterine Programming, Genomic Imprinting, Non-Coding RNAAbstract
It is estimated that around 70% of all adults around the world have faced trauma in their lives (Benjet et al., 2016). Trauma can cause individuals to undergo epigenetic changes which can lead to health complications in the future (Alegría-Torres et al., 2011). Epigenetics is defined as the study of molecular modifications to DNA through DNA methylation, histone modifications, and non-coding RNAs that can regulate gene expression independent of DNA sequences (Li, 2021). New evidence suggests that epigenetic changes may be passed down to offspring. However, the exact pathway for transgenerational epigenetic inheritance to occur is unknown. While existing theories, including intrauterine programming, miRNA-mediated pathways, and genomic imprinting, offer possible pathways, none can fully account for the spectrum of transgenerational inheritance. This paper will review the three models proposed and will explore the possibility of their combined influence on transgenerational epigenetic inheritance. Exploring epigenetic mechanisms can help offer potential intervention points to relieve the negative impact of trauma on several generations.
Downloads
References or Bibliography
Agrawal, A., Murphy, R. F., & Agrawal, D. K. (2007). DNA methylation in breast and colorectal cancers. Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc, 20(7). https://doi.org/10.1038/modpathol.3800822
Alegría-Torres, J. A., Baccarelli, A., & Bollati, V. (2011). Epigenetics and lifestyle. Epigenomics, 3(3), 267.
Ali, A., Hadlich, F., Abbas, M. W., Iqbal, M. A., Tesfaye, D., Bouma, G. J., Winger, Q. A., & Ponsuksili, S. (2021). MicroRNA–mRNA Networks in Pregnancy Complications: A Comprehensive Downstream Analysis of Potential Biomarkers. International Journal of Molecular Sciences, 22(5). https://doi.org/10.3390/ijms22052313
Allen, M. J., & Sharma, S. (2023). Physiology, Adrenocorticotropic Hormone (ACTH). In StatPearls [Internet]. StatPearls Publishing.
Bajrami, E., & Spiroski, M. (2016). Genomic Imprinting. Open Access Macedonian Journal of Medical Sciences, 4(1), 181.
Bannister, A. J., & Kouzarides, T. (2011). Regulation of chromatin by histone modifications. Cell Research, 21(3). https://doi.org/10.1038/cr.2011.22
Benjet, C., Bromet, E., Karam, E. G., Kessler, R. C., McLaughlin, K. A., Ruscio, A. M., Shahly, V., Stein, D. J., Petukhova, M., Hill, E., Alonso, J., Atwoli, L., Bunting, B., Bruffaerts, R., Caldas-de-Almeida, J. M., de Girolamo, G., Florescu, S., Gureje, O., Huang, Y., … Koenen, K. C. (2016). The epidemiology of traumatic event exposure worldwide: results from the World Mental Health Survey Consortium. Psychological Medicine, 46(2), 327.
Blackmore, E. R., Putnam, F. W., Pressman, E. K., Rubinow, D. R., Putnam, K. T., Matthieu, M. M., Gilchrist, M. A., Jones, I., & O’Connor, T. G. (2016). The Effects of Trauma History and Prenatal Affective Symptoms on Obstetric Outcomes. Journal of Traumatic Stress, 29(3), 245.
Bure, I. V., Nemtsova, M. V., & Kuznetsova, E. B. (2022). Histone Modifications and Non-Coding RNAs: Mutual Epigenetic Regulation and Role in Pathogenesis. International Journal of Molecular Sciences, 23(10). https://doi.org/10.3390/ijms23105801
Butler, M. G. (2011). Prader-Willi Syndrome: Obesity due to Genomic Imprinting. Current Genomics, 12(3), 204.
Chen, Q., Yan, M., Cao, Z., Li, X., Zhang, Y., Shi, J., Feng, G.-H., Peng, H., Zhang, X., Zhang, Y., Qian, J., Duan, E., Zhai, Q., & Zhou, Q. (2016). Sperm tsRNAs contribute to intergenerational inheritance of an acquired metabolic disorder. Science. https://doi.org/10.1126/science.aad7977
Deodati, A., Inzaghi, E., & Cianfarani, S. (2019). Epigenetics and In Utero Acquired Predisposition to Metabolic Disease. Frontiers in Genetics, 10. https://doi.org/10.3389/fgene.2019.01270
Dias, B. G., & Ressler, K. J. (2014). Parental olfactory experience influences behavior and neural structure in subsequent generations. Nature Neuroscience, 17(1). https://doi.org/10.1038/nn.3594
Driscoll, D. J., Miller, J. L., & Cassidy, S. B. (2023). Prader-Willi Syndrome. In GeneReviews® [Internet]. University of Washington, Seattle.
Duempelmann, L., Skribbe, M., & Bühler, M. (2020). Small RNAs in the Transgenerational Inheritance of Epigenetic Information. Trends in Genetics: TIG, 36(3). https://doi.org/10.1016/j.tig.2019.12.001
Faisal, M., Kim, H., & Kim, J. (2014). Sexual differences of imprinted genes’ expression levels. Gene, 533(1). https://doi.org/10.1016/j.gene.2013.10.006
Ferguson-Smith, A. C., & Bourc’his, D. (2018). The discovery and importance of genomic imprinting. eLife, 7. https://doi.org/10.7554/eLife.42368
Gapp, K., Jawaid, A., Sarkies, P., Bohacek, J., Pelczar, P., Prados, J., Farinelli, L., Miska, E., & Mansuy, I. M. (2014). Implication of sperm RNAs in transgenerational inheritance of the effects of early trauma in mice. Nature Neuroscience, 17(5), 667.
Ghai, M., & Kader, F. (2021). A Review on Epigenetic Inheritance of Experiences in Humans. Biochemical Genetics, 60(4), 1107–1140.
Gluckman, P. D., Hanson, M. A., Cooper, C., & Thornburg, K. L. (2008). Effect of In Utero and Early-Life Conditions on Adult Health and Disease. The New England Journal of Medicine, 359(1), 61.
Grandjean, V., Gounon, P., Wagner, N., Martin, L., Wagner, K. D., Bernex, F., Cuzin, F., & Rassoulzadegan, M. (2009). The miR-124-Sox9 paramutation: RNA-mediated epigenetic control of embryonic and adult growth. Development , 136(21), 3647–3655.
Heard, E., & Martienssen, R. A. (2014). Transgenerational Epigenetic Inheritance: myths and mechanisms. Cell, 157(1), 95.
Herman, J. P., McKlveen, J. M., Ghosal, S., Kopp, B., Wulsin, A., Makinson, R., Scheimann, J., & Myers, B. (2016). Regulation of the hypothalamic-pituitary-adrenocortical stress response. Comprehensive Physiology, 6(2), 603.
Highly conserved sperm function-related transcripts across three species: human, rat and mouse. (2021). Reproductive Toxicology , 104, 44–51.
Howland, M. A., Sandman, C. A., & Glynn, L. M. (2017). Developmental origins of the human hypothalamic-pituitary-adrenal axis. Expert Review of Endocrinology & Metabolism, 12(5), 321.
Jiang, W., Han, T., Duan, W., Dong, Q., Hou, W., Wu, H., Wang, Y., Jiang, Z., Pei, X., Chen, Y., Li, Y., & Sun, C. (2020). Prenatal famine exposure and estimated glomerular filtration rate across consecutive generations: association and epigenetic mediation in a population-based cohort study in Suihua China. Aging, 12(12), 12206.
Kaati, G., Bygren, L. O., & Edvinsson, S. (2002). Cardiovascular and diabetes mortality determined by nutrition during parents’ and grandparents' slow growth period. European Journal of Human Genetics: EJHG, 10(11), 682–688.
Kaikkonen, M. U., Lam, M. T. Y., & Glass, C. K. (2011). Editor’s Choice: Non-coding RNAs as regulators of gene expression and epigenetics. Cardiovascular Research, 90(3), 430.
Kelsey, G., & Feil, R. (2013). New insights into establishment and maintenance of DNA methylation imprints in mammals. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, 368(1609). https://doi.org/10.1098/rstb.2011.0336
Kessler, R. C., Aguilar-Gaxiola, S., Alonso, J., Benjet, C., Bromet, E. J., Cardoso, G., Degenhardt, L., de Girolamo, G., Dinolova, R. V., Ferry, F., Florescu, S., Gureje, O., Haro, J. M., Huang, Y., Karam, E. G., Kawakami, N., Lee, S., Lepine, J. P., Levinson, D., … Koenen, K. C. (2017). Trauma and PTSD in the WHO World Mental Health Surveys. European Journal of Psychotraumatology, 8(sup5). https://doi.org/10.1080/20008198.2017.1353383
Kobayashi, H. (2021). Canonical and Non-canonical Genomic Imprinting in Rodents. Frontiers in Cell and Developmental Biology, 9, 713878.
Lee, G. S., & Conine, C. C. (2022). The Transmission of Intergenerational Epigenetic Information by Sperm microRNAs. Epigenomes, 6(2). https://doi.org/10.3390/epigenomes6020012
Li, Y. (2021). Modern epigenetics methods in biological research. Methods , 187. https://doi.org/10.1016/j.ymeth.2020.06.022
Li, Y., & Sasaki, H. (2011). Genomic imprinting in mammals: its life cycle, molecular mechanisms and reprogramming. Cell Research, 21(3). https://doi.org/10.1038/cr.2011.15
Lock, M. C., Botting, K. J., Tellam, R. L., Brooks, D., & Morrison, J. L. (2017). Adverse Intrauterine Environment and Cardiac miRNA Expression. International Journal of Molecular Sciences, 18(12). https://doi.org/10.3390/ijms18122628
Louis, G. M. B., Cooney, M. A., Lynch, C. D., & Handal, A. (2008). Periconception Window: Advising the Pregnancy Planning Couple. Fertility and Sterility, 89(2 Suppl), e119.
MacDonald, W. A. (2012). Epigenetic Mechanisms of Genomic Imprinting: Common Themes in the Regulation of Imprinted Regions in Mammals, Plants, and Insects. Genetics Research International, 2012. https://doi.org/10.1155/2012/585024
Maffioletti, E., Bocchio-Chiavetto, L., Perusi, G., Silva, R. C., Sacco, C., Bazzanella, R., Zampieri, E., Bortolomasi, M., Gennarelli, M., & Minelli, A. (2021). Inflammation-related microRNAs are involved in stressful life events exposure and in trauma-focused psychotherapy in treatment-resistant depressed patients. European Journal of Psychotraumatology, 12(1). https://doi.org/10.1080/20008198.2021.1987655
Morgan, C. P., Shetty, A. C., Chan, J. C., Berger, D. S., Ament, S. A., Neill Epperson, C., & Bale, T. L. (2020). Repeated sampling facilitates within- and between-subject modeling of the human sperm transcriptome to identify dynamic and stress-responsive sncRNAs. Scientific Reports, 10. https://doi.org/10.1038/s41598-020-73867-7
Painter, R. C., Osmond, C., Gluckman, P., Hanson, M., Phillips, D. I. W., & Roseboom, T. J. (2008). Transgenerational effects of prenatal exposure to the Dutch famine on neonatal adiposity and health in later life. BJOG: An International Journal of Obstetrics and Gynaecology, 115(10), 1243–1249.
Raad, G., Serra, F., Martin, L., Derieppe, M.-A., Gilleron, J., Costa, V. L., Pisani, D. F., Amri, E.-Z., Trabucchi, M., & Grandjean, V. (2021). Paternal multigenerational exposure to an obesogenic diet drives epigenetic predisposition to metabolic diseases in mice. eLife, 10. https://doi.org/10.7554/eLife.61736
Raff, H., & Carroll, T. (2015). Cushing’s syndrome: from physiological principles to diagnosis and clinical care. The Journal of Physiology, 593(3), 493–506.
Rodgers, A. B., Morgan, C. P., Bronson, S. L., Revello, S., & Bale, T. L. (2013). Paternal Stress Exposure Alters Sperm MicroRNA Content and Reprograms Offspring HPA Stress Axis Regulation. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 33(21), 9003.
Rodgers, A. B., Morgan, C. P., Leu, N. A., & Bale, T. L. (2015). Transgenerational epigenetic programming via sperm microRNA recapitulates effects of paternal stress. Proceedings of the National Academy of Sciences of the United States of America, 112(44). https://doi.org/10.1073/pnas.1508347112
Sedaghat, K., Zahediasl, S., & Ghasemi, A. (2015). Intrauterine programming. Iranian Journal of Basic Medical Sciences, 18(3), 212.
Seisenberger, S., Peat, J. R., Hore, T. A., Santos, F., Dean, W., & Reik, W. (2013). Reprogramming DNA methylation in the mammalian life cycle: building and breaking epigenetic barriers. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, 368(1609). https://doi.org/10.1098/rstb.2011.0330
Sinha, S., Patro, N., & Patro, I. K. (2018). Maternal Protein Malnutrition: Current and Future Perspectives of Spirulina Supplementation in Neuroprotection. Frontiers in Neuroscience, 12. https://doi.org/10.3389/fnins.2018.00966
Skinner, M. K., Ben, M. M., Sadler-Riggleman, I., Beck, D., Nilsson, E., McBirney, M., Klukovich, R., Xie, Y., Tang, C., & Yan, W. (2018). Alterations in sperm DNA methylation, non-coding RNA and histone retention associate with DDT-induced epigenetic transgenerational inheritance of disease. Epigenetics & Chromatin, 11(1). https://doi.org/10.1186/s13072-018-0178-0
Solomon, Z., Kotler, M., & Mikulincer, M. (1988). Combat-related posttraumatic stress disorder among second-generation Holocaust survivors: preliminary findings. The American Journal of Psychiatry, 145(7). https://doi.org/10.1176/ajp.145.7.865
Tobi, E. W., Lumey, L. H., Talens, R. P., Kremer, D., Putter, H., Stein, A. D., Slagboom, P. E., & Heijmans, B. T. (2009). DNA methylation differences after exposure to prenatal famine are common and timing- and sex-specific. Human Molecular Genetics, 18(21), 4046–4053.
Toraño, E. G., García, M. G., Fernández-Morera, J. L., Niño-García, P., & Fernández, A. F. (2016). The Impact of External Factors on the Epigenome: In Utero and over Lifetime. BioMed Research International, 2016. https://doi.org/10.1155/2016/2568635
Vangeel, E. B., Izzi, B., Hompes, T., Vansteelandt, K., Lambrechts, D., Freson, K., & Claes, S. (2015). DNA methylation in imprinted genes IGF2 and GNASXL is associated with prenatal maternal stress. Genes, Brain, and Behavior, 14(8), 573–582.
Weinhold, B. (2006). Epigenetics: The Science of Change. Environmental Health Perspectives, 114(3), A160.
Yehuda, R., Daskalakis, N. P., Lehrner, A., Desarnaud, F., Bader, H. N., Makotkine, I., Flory, J. D., Bierer, L. M., & Meaney, M. J. (2014). Influences of Maternal and Paternal PTSD on Epigenetic Regulation of the Glucocorticoid Receptor Gene in Holocaust Survivor Offspring. The American Journal of Psychiatry. https://doi.org/10.1176/appi.ajp.2014.13121571
Ying, S.-Y., Chang, D. C., & Lin, S.-L. (2008). The MicroRNA (miRNA): Overview of the RNA Genes that Modulate Gene Function. Molecular Biotechnology, 38(3), 257.
Youssef, N. A., Lockwood, L., Su, S., Hao, G., & Rutten, B. P. F. (2018). The Effects of Trauma, with or without PTSD, on the Transgenerational DNA Methylation Alterations in Human Offsprings. Brain Sciences, 8(5). https://doi.org/10.3390/brainsci8050083
Zuo, X., Sheng, J., Lau, H.-T., McDonald, C. M., Andrade, M., Cullen, D. E., Bell, F. T., Iacovino, M., Kyba, M., Xu, G., & Li, X. (2012). Zinc Finger Protein ZFP57 Requires Its Co-factor to Recruit DNA Methyltransferases and Maintains DNA Methylation Imprint in Embryonic Stem Cells via Its Transcriptional Repression Domain. The Journal of Biological Chemistry, 287(3), 2107.
Published
How to Cite
Issue
Section
Copyright (c) 2024 Sampriti Muthuswamy; Ms.Nicole Katchur
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Copyright holder(s) granted JSR a perpetual, non-exclusive license to distriute & display this article.