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

Area of Science:

• Reproductive biology and developmental toxicology
• Endocrinology and metabolic research
• Perinatal medicine

Background:

• Melatonin is crucial for healthy pregnancy and fetal development, exhibiting antioxidant, anti-inflammatory, and chronobiotic properties.
• Excessive oxidative stress during development can lead to maladaptive fetal programming, increasing lifelong risks for cardiovascular, kidney, and metabolic (CKM) disorders.
• Current evidence on maternal melatonin's protective effects is largely from rodent models and shows variable results.

Purpose of the Study:

• To review mechanistic and translational evidence on melatonin's role in mitigating intergenerational risks of CKM disorders.
• To explore melatonin's potential as a preventive strategy against adverse fetal programming.
• To synthesize findings on melatonin's impact on redox homeostasis, epigenetic pathways, and the gut microbiome.

Main Methods:

• Synthesis of mechanistic studies from experimental models.
• Review of early clinical investigations in human pregnancies.
• Analysis of melatonin's effects on oxidative stress, epigenetic modifications, nutrient sensing, and gut microbiota.

Main Results:

• Experimental studies suggest maternal melatonin can prevent programmed hypertension, renal dysfunction, and metabolic issues by restoring redox balance.
• Melatonin influences epigenetic and nutrient-sensing pathways and modulates the gut microbiome.
• Initial clinical studies indicate melatonin is well-tolerated in pregnancies with preeclampsia or intrauterine growth restriction, improving placental function and neonatal outcomes.

Conclusions:

• Maternal melatonin supplementation shows potential in preventing programmed CKM disorders by addressing oxidative stress and related pathways.
• Clinical investigations suggest benefits for placental function and neonatal outcomes, though optimal dosing and long-term safety require further study.
• Melatonin emerges as a potential integrative mediator for preventive strategies against the intergenerational transmission of CKM syndrome.