Maternal perinatal undernutrition alters neuronal and neuroendocrine differentiation in the rat adrenal medulla at weaning.

Epidemiological studies suggest that chronic adult diseases, such as type 2 diabetes and hypertension, can be programmed during fetal and early postnatal life. The nervous system regions governing vegetative functions and the hypothalamic-pituitary-adrenal axis are particularly sensitive to the perinatal nutritional status. Despite recent reports demonstrating that the activity of the sympathoadrenal system can be altered by early life events, the effects of maternal nutrient restriction on the adrenal medulla remain unknown. Using a rat model of maternal perinatal 50% food restriction (FR50) from the second week of gestation until weaning, immunohistochemical experiments revealed alterations in chromaffin cell aggregation and in nerve fiber fasciculation in the adrenal medulla of FR50 pups. These morphological changes were associated with enhanced circulating levels of catecholamines after decapitation (epinephrine by 55% and norepinephrine by 41%). Using macroarrays, we identified several genes whose expression was affected by maternal nutrient restriction. Semiquantitative RT-PCR confirmed the overexpression of four genes involved in neuroendocrine differentiation and neuronal plasticity (chromogranin B, growth-associated protein 43, neurofilament 3, and Slit2) in the adrenal glands of FR50 rats. Using in situ hybridization, we showed that these genes are solely expressed in the adrenal medulla. Together, our results suggest that perinatal maternal undernutrition markedly alters the differentiation of the adrenal medulla during postnatal life, resulting in enhanced activity of chromaffin cells at weaning. These alterations may persist in adulthood and participate to the programming of chronic adult diseases.