Fetal programming and functional teratogenesis: on epigenetic mechanisms and prevention of perinatally acquired lasting health risks

Alterations of the intrauterine and early postnatal nutritional, metabolic, and hormonal environment may cause predispositions to the development of disorders and diseases in later life. Mechanisms responsible for this perinatally acquired malprogramming still remain unclear. It has long been known, however, that hormones are environment dependent organizers of the developing neuroendocrineimmune network, which regulates all fundamental processes of life. When present in nonphysiological concentrations during critical ontogenetic periods, hormones can therefore also act as endogenous functional teratogens. Fetal and neonatal hyperinsulinism is a pathognomic feature in the offspring of diabetic mothers. Perinatal hyperinsulinism also occurs due to early postnatal overfeeding. Data obtained by our group indicate that elevated insulin concentrations during critical periods of perinatal life may induce a lasting malprogramming of neuroendocrine systems regulating body weight, food intake, and metabolism. Similar characteristics may occur due to perinatal hyperleptinism, hypercortisolism etc. Since mechanisms of early programming of obesity, diabetes, and the metabolic syndrome X are unclear, a complex neuroendocrine malprogramming of the regulation of body weight and metabolism may provide a general etiopathogenetic concept in this context, exemplarily revealing critical new implications for chances and challenges of perinatal preventive medicine in the future.