Maternal Perinatal Undernutrition Alters Postnatal Development of Chromaffin Cells in the Male Rat Adrenal Medulla

Abstract

Numerous data suggest that the development of the sympathoadrenal system is highly sensitive to the perinatal environment. We previously reported that maternal perinatal food restriction by 50% (FR50) altered chromaffin cell (CC) organization and activity in offspring at weaning. This study investigated the effects of FR50 on the postnatal time course of CC functional and structural adaptations. FR50 pups exhibited smaller and more abundant scattered clusters of noradrenergic CCs as early as postnatal day 7 (P7), indicating that morphological changes took place earlier during development. At birth, the adrenaline release was defective in FR50 pups, suggesting that maternal FR50 impaired the non-neurogenic control of catecholamine release. At P4, the catecholamine release in response to insulin-induced hypoglycaemia was also absent in FR50 pups. This was associated with the reduction of adrenal catecholamine contents, indicating that the failure to synthesize catecholamine might lead to impaired secretion. We hypothesized that maternal FR50 accelerated the functional connections between CCs and splanchnic nerve endings, leading to the premature loss of the non-neurogenic response. Acetylcholine-containing synaptic endings seemed more precociously functional in FR50 pups, as suggested by increased levels of acetylcholine esterase activity at P14. At P7, insulin-induced hypoglycaemia caused preferential adrenaline release associated with increased catecholamine contents in both groups. However, the response was accentuated in FR50 pups. At P14, the insulin challenge increased plasma levels of adrenaline in control rats, whereas it markedly enhanced the circulating level of both catecholamines in FR50 pups. We demonstrated that maternal FR50 leads to developmentally impaired noradrenergic CC aggregation and advanced splanchnic neurotransmission maturation associated with altered medulla activity in response to metabolic stress. This might contribute to the long-lasting malprogramming of the adrenal medulla and to the development of chronic adult diseases.

Programming of rat adrenal medulla by neonatal hyperleptinemia: adrenal morphology, catecholamine secretion, and leptin signaling pathway

“…Undernutrition during gestation and lactation induces changes in the development of adrenal chromaffin cells, resulting in increased catecholamine levels at weaning (34,35). We have also observed that maternal protein restriction only during lactation programs for high catecholamine synthesis and secretion at adulthood (22).…”

“…We suppose that the hyperleptinemia of programmed rats could lead to an increase of catecholamine production through SNS activation, and the lower OBR and JAK2 medullary content counterbalance this stimulatory effect to avoid adverse cardiovascular and metabolic consequences. Besides, Molendi-Coste et al (35) have shown that undernutrition in early life advanced splanchnic neurotransmission maturation during development, and a similar mechanism may be involved in our programming model.…”

Post-Weaning Protein Malnutrition Increases Blood Pressure and Induces Endothelial Dysfunctions in Rats

“…A previous report [27] has shown that the intrauterine malnutrition with a low protein (8% casein) diet in rats promotes an increase in blood pressure of the offspring at a young adulthood stage. Previous reports evaluating the effects of protein-caloric deprivation in rats have suggested an increased hypothalamic-pituitary-adrenal response and circulating catecholamines [28]–[30]. Then, the increase in heart rate and blood pressure might be related to increased sympathetic nervous system activity [31].…”

Maternal Chromium Restriction Leads to Glucose Metabolism Imbalance in Mice Offspring through Insulin Signaling and Wnt Signaling Pathways

“…Increasing evidence suggests that the occurrence of diabetes is related to nutrition status in fetus period [1,2,3,4]. Growing evidence proves that under-nutrition in early life is an important risk of metabolic disease in later life [5,6].…”