Prenatal caffeine exposure-induced adrenal developmental abnormality in male offspring rats and its possible intrauterine programming mechanisms

Citations Over TimeTop 10% of 2016 papers

Abstract

Glucocorticoid (GC) is a major factor for fetal tissue maturation and fate decision after birth. We previously demonstrated that prenatal caffeine exposure (PCE) suppressed fetal adrenal steroidogenesis and resulted in adrenal dysplasia. However, whether these changes play a role until adulthood and its intrauterine programming mechanisms remain unknown. In the present study, a rat model of intrauterine growth retardation (IUGR) was established by PCE, male fetuses and adult offspring were sacrificed at postnatal day (PD) 1, PD7, PD35, PD100 and PD168, respectively. Results showed that the PCE fetal weight decreased and the IUGR rate increased, while the serum corticosterone (CORT) level increased but the insulin-like growth factor 1 (IGF1) level decreased. Fetal adrenal exhibited an enhanced GC-activation system (11β-hydroxysteroid dehydrogenases/corticoid receptors/CCAAT/enhancer binding proteins), an inhibited IGF1 pathway and steroid synthesis function. After birth, the serum CORT levels in the PCE offspring were increased in the early period followed by falling in the later stage, while the serum IGF1 level change was the opposite and was accompanied by an obvious catch-up growth. Furthermore, the adrenal GC-activation system was inhibited but the IGF1 signaling pathway was enhanced, resulting in a compensatory increase of adrenal steroidogenesis, and the expression of steroidal synthetase was consistent with that of the IGF1 signaling pathway. Based on these findings, we proposed "two-programming mechanisms" for PCE-induced adrenal abnormality: the "first programming" mechanism is a lower function of adrenal steroidogenesis, and prenatal and postnatal adrenal structural and functional abnormalities triggered by the intrauterine GC-IGF1 axis programming-mediated by the GC-activation system that acts as "the second programming" mechanism.

Related Papers

• → Impact of caffeine and coffee on our health(2014)295 cited
• → Quantitative Analysis of Caffeine in different commercial kinds of coffee in Iraq(2023)2 cited
• → Effect of caffeine on coffee drinking(1976)31 cited
• → Preclinical safety assessment of gene and cell therapy products(2011)
• → Effect of the age of pregnant females on brain development in the offspring(2004)