Decreased hippocampal mineralocorticoid:glucocorticoid receptor ratio is associated with low birth weight in female cynomolgus macaque neonates

Abstract

During pregnancy, glucocorticoids transfer environmental signals to the growing brain and its associated neuroendocrine system to modulate their maturation and function during adolescence and adulthood. Increased in utero exposure to glucocorticoids is associated with impaired fetal growth resulting in low birth weight (LBW) and compromised neural development. The underlying molecular changes affecting brain development, however, are largely unknown. Here, we compared the relative mRNA expression of genes directly involved in glucocorticoid signaling in the hippocampus, amygdala, and cortex of female non-human primate neonates (Macaca fascicularis) of naturally occurring normal birth weight and LBW. We focused on the glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) genes as well as that for 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) and found a significantly decreased MR:GR mRNA ratio in the hippocampus and lower expression of 11β-HSD1 in the amygdala associated with LBW. The MR:GR mRNA ratio in the amygdala and cortex was not associated with birth weight, reflecting tissue-specific effects. Protein quantification in the hippocampus confirmed our finding of a decreased hippocampal MR:GR ratio. Our data suggest that the MR:GR ratio in the hippocampus and the expression of 11β-HSD1 in the amygdala are associated with intrauterine growth restriction in non-human primates during early perinatal development.

Keywords: MR:GR ratio; cynomolgus macaque; glucocorticoid receptor; low birth weight.