Chronobiological and endocrine consequences of prenatal hypoxia: melatonin – insulin – adrenalin – glucose axis

Prenatal hypoxia is a critical developmental stressor that disrupts the maturation of neuroendocrine and metabolic systems. Evidence indicates that oxygen deprivation during embryogenesis alters the melatonin–insulin–adrenalin–glucose (MIAG) axis, leading to impaired circadian synchronization, β-cell dysfunction, and dysregulation of stress-responsive pathways. This review summarizes current findings on how prenatal hypoxia reshapes melatonin rhythms, affects peripheral clock resetting, and modifies hypothalamic–pituitary–adrenal (HPA) and pancreatic endocrine activity. Recent studies indicate that hypoxia modulates melatonin secretion, attenuates insulin sensitivity, enhances catecholamine reactivity, and disrupts glucose homeostasis. Understanding these chronobiological interactions provides insight into developmental programming mechanisms and highlights melatonin as a potential target for time-dependent interventions. These observations highlight the critical role of the melatonin–insulin and melatonin-adrenalin feedback loop in maintaining glucose homeostasis and underscore the broader concept of a chronometabolic axis integrating circadian and endocrine regulation. The evidence from animal models suggests that melatonin acts not merely as a nocturnal signal, but as a key modulator of pancreatic sensitivity and metabolic timing under given the different types of stress of antenatal and postnatal development of ontogenesis. Therefore, disturbances in melatonin receptor function or misalignment of its circadian rhythm could have far-reaching consequences for insulin and adrenaline secretion, glucose tolerance, and overall metabolic resilience.