title: Developmental Programming of Adult Disease: Reprogramming by Melatonin?
abstract: Adult-onset chronic non-communicable diseases (NCDs) can originate from early life through so-called the "developmental origins of health and disease" (DOHaD) or "developmental programming". The DOHaD concept offers the "reprogramming" strategy to shift the treatment from adulthood to early life, before clinical disease is apparent. Melatonin, an endogenous indoleamine produced by the pineal gland, has pleiotropic bioactivities those are beneficial in a variety of human diseases. Emerging evidence support that melatonin is closely inter-related to other proposed mechanisms contributing to the developmental programming of a variety of chronic NCDs. Recent animal studies have begun to unravel the multifunctional roles of melatonin in many experimental models of developmental programming. Even though some progress has been made in research on melatonin as a reprogramming strategy to prevent DOHaD-related NCDs, future human studies should aim at filling the translational gap between animal models and clinical trials. Here, we review several key themes on the reprogramming effects of melatonin in DOHaD research. We have particularly focused on the following areas: mechanisms of developmental programming; the interrelationship between melatonin and mechanisms underlying developmental programming; pathophysiological roles of melatonin in pregnancy and fetal development; and insight provided by animal models to support melatonin as a reprogramming therapy. Rates of NCDs are increasing faster than anticipated all over the world. Hence, there is an urgent need to understand reprogramming mechanisms of melatonin and to translate experimental research into clinical practice for halting a growing list of DOHaD-related NCDs.
authors.affiliation: Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan. tainyl@hotmail.com.|Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan. tainyl@hotmail.com.
authors.forename: You-Lin
authors.initials: YL
authors.lastname: Tain
authors.affiliation: Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan. litung.huang@gmail.com.|Department of Traditional Chinese Medicine, Chang Gung University, Linkow 244, Taiwan. litung.huang@gmail.com.
authors.forename: Li-Tung
authors.initials: LT
authors.lastname: Huang
authors.affiliation: Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan. chien_ning_hsu@hotmail.com.|School of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan. chien_ning_hsu@hotmail.com.
authors.forename: Chien-Ning
authors.initials: CN
authors.lastname: Hsu
mesh_terms: D000328:Adult; D000818:Animals; D004198:Disease Susceptibility; D005260:Female; D047109:Fetal Development; D006801:Humans; D008550:Melatonin / Q000235:genetics* / Q000378:metabolism* / Q000627:therapeutic use; D023421:Models, Animal; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D015398:Signal Transduction
chemical_list: D008550:Melatonin
keywords: cardiovascular disease; developmental origins of health and disease (DOHaD); developmental programming; epigenetic regulation; glucocorticoid; hypertension; melatonin; next-generation sequencing; non-communicable disease; oxidative stress; renin-angiotensin system