Preemptive Epigenetic Medicine Based on Fetal Programming
The developmental origins of health and disease (DOHaD) refers to the concept that environmental stress during pregnancy alters the programmed fetal development and subsequently causes disorders, such as cardiovascular and metabolic diseases, in adulthood
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epigenetic disorders. Therefore, preventive and preemptive medicine is possible for disorders caused by alterations in programming during fetal and early periods.
Abstract
The developmental origins of health and disease (DOHaD) refers to the concept that environmental stress during pregnancy alters the programmed fetal development and subsequently causes disorders, such as cardiovascular and metabolic diseases, in adulthood. Epigenetics is a gene regulation mechanism that does not depend on DNA sequence but on chemical modifications of DNA. Several lines of evidence suggest that environmental stress in the fetal period alters the epigenetic state of genes, leading to permanent gene dysregulation, which may be associated with disorders that emerge after birth. Such stresses include malnutrition, which may be associated with type 2 diabetes, and mental stress, which may be associated with neurodevelopmental disorders. It has also been demonstrated that environmental stress-induced epigenetic alterations can be transmitted to the next generation via disease phenotypes. However, since epigenetic modification is an internal system based on attachment and detachment of chemical residues on a DNA sequence, it is reversible and potentially treatable. In fact, recent studies demonstrated that some drugs and early interventions are effective at preventing T. Kubota (*) Faculty of Child Studies, Seitoku University, Matsudo, Chiba, Japan e-mail: [email protected]
Keywords
DOHaD · Epigenetics · Epigenome · Reversibility · Preemptive medicine
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Introduction
It is known that environmental stress during pregnancy (e.g., drug exposure or viral infections) can cause congenital anomalies in the fetus. For example, valproic acid, a drug commonly used for epilepsy and psychiatric disorders, is associated with the occurrence of spina bifida, congenital heart defects, and cleft lip/plate. Rubella viral infection is known to increase the risk of congenital heart defects, deafness, and congenital cataract. Similarly, bisphenol A, a plastic plasticizer that is an environmental chemical, is known to increase the risk of urological anomalies, such as cryptorchidism and hypospadias, in fetuses [1]. Because of these findings, pharmaceutical companies disclose fetus-related side effects of prescription drugs in patient package inserts; in addition, the rubella vaccination is now recommended prior to pregnancy in young women (Fig. 1, top).
© Springer Nature Singapore Pte Ltd. 2018 T. Kubota, H. Fukuoka (eds.), Developmental Origins of Health and Disease (DOHaD), Advances in Experimental Medicine and Biology 1012, https://doi.org/10.1007/978-981-10-5526-3_9
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T. Kubota
86 Fig. 1 Environmental factors, such as drug exposure and viral infection during pregnancy, are known to cause congenital anomalies in fetuses. Under the current concept of the developmental origins of health and disease (DOHaD), maternal environmental stress during pregnancy can cause adult-onset disorders in the fetus
Environmental factors (traditional) Dru
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