# Melatonin as a Redox Modulator in Developmental Programming: Implications for Cardiovascular–Kidney–Metabolic Risk

## TL;DR

Melatonin may help prevent health risks in offspring by reducing oxidative stress during pregnancy, potentially lowering future cardiovascular, kidney, and metabolic issues.

## Contribution

This paper reviews melatonin's role as a redox modulator in developmental programming, highlighting its potential for mitigating CKM risk across generations.

## Key findings

- Maternal melatonin supplementation can restore redox homeostasis and improve fetal outcomes in rodent models.
- Melatonin influences epigenetic pathways and gut microbiome, potentially preventing programmed hypertension and metabolic issues.
- Early clinical trials show melatonin is well-tolerated and beneficial in pregnancies with complications like preeclampsia.

## Abstract

Melatonin, a multifunctional hormone with antioxidant, anti-inflammatory, and chronobiotic effects, is essential for a healthy pregnancy and fetal development. In the context of the Developmental Origins of Health and Disease (DOHaD), excessive oxidative stress acts as a key driver of maladaptive fetal programming, increasing lifelong susceptibility to cardiovascular, kidney, and metabolic (CKM) disorders. Importantly, most evidence derives from rodent models, and the protective effects of maternal melatonin supplementation appear partial and model-dependent rather than universal. Experimental studies indicate that maternal melatonin supplementation can prevent programmed hypertension, renal dysfunction, and metabolic derangements by restoring redox homeostasis, influencing epigenetic and nutrient-sensing pathways, and modulating the gut microbiome. Early clinical investigations in pregnancies complicated by preeclampsia or intrauterine growth restriction suggest that melatonin is well tolerated, improves placental function, and benefits neonatal outcomes. However, optimal dosing and long-term safety for offspring remain to be established. This review synthesizes mechanistic and translational evidence, framing melatonin as an integrative biological mediator with potential to guide preventive strategies and mitigate the intergenerational risk of CKM syndrome.