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.

Light and Circadian Signaling Pathway in Pregnancy: Programming of Adult Health and Disease

“…Additionally, melatonin can interact with the nuclear hormone receptor family retinoid Z receptor (RZR)/retinoid acid receptor (ROR) for signal transduction [28]. Melatonin has pleiotropic biological functions that control circadian rhythms, redox homeostasis, inflammation, epigenetic regulation, and fetal development [4,[29][30][31]].…”

Maternal Obesity Programs Offspring Development and Resveratrol Potentially Reprograms the Effects of Maternal Obesity

“…Reprogramming strategies refers to maneuvers to reverse malprogrammed development to resume normal development [66,67]. These strategies could be nutritional interventions, lifestyle modifications, or pharmacological interventions [68].…”

“…These strategies could be nutritional interventions, lifestyle modifications, or pharmacological interventions [68]. A mechanistic understanding of how the maternal intrauterine and lactational environment may be mediating offspring common morbidities is critical, because early life may represent an important window for targeted intervention to ameliorate fetal and offspring risk [66]. A previous review suggests that early-life resveratrol supplementation could be considered as a reprogramming strategy against the development of metabolic syndrome-related disorders [67].…”

The Role of Prenatal Melatonin in the Regulation of Childhood Obesity

“…The absence of a circadian melatonin rhythm in obese mothers was also associated no circadian melatonin rhythm in their offspring, whilst the offspring of nonobese mothers showed a low but significant circadian melatonin rhythm from the 3rd postnatal day [74]. Such data highlights the importance of the melatonin circadian rhythm over pregnancy as well as postnatally [75][76][77].…”