Transgenerational effects of prenatal synthetic glucocorticoids on hypothalamic-pituitary-adrenal function.

Endocrinology
Majid IqbalS G Matthews

Abstract

Approximately 10% of pregnant women are at risk of preterm delivery and receive synthetic glucocorticoids (sGC) to promote fetal lung development. Studies have indicated that prenatal sGC therapy modifies hypothalamic-pituitary-adrenal (HPA) function in first-generation (F(1)) offspring. The objective of this study was to determine whether differences in HPA function and behavior are evident in the subsequent (F(2)) generation. Pregnant guinea pigs (F(0)) received betamethasone (BETA; 1 mg/kg) or saline on gestational d 40/41, 50/51, and 60/61. F(1) females were mated with control males to create F(2) offspring. HPA function was assessed in juvenile and adult F(2) offspring. Locomotor activity was assessed in juvenile offspring. Analysis of HPA-related gene expression was undertaken in adult hippocampi, hypothalami, and pituitaries. Locomotor activity was reduced in F(2) BETA males (P < 0.05). F(2) BETA offspring displayed blunted cortisol response to swim stress (P < 0.05). After dexamethasone challenge, F(2) BETA males and females displayed increased and decreased negative feedback, respectively. F(2) BETA females had reduced pituitary levels of proopiomelanocortin (and adrenocorticotropic hormone), and corticotropin-releasin...Continue Reading

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Methods Mentioned

BETA
ELISA
antisense oligonucleotide
histone acetylation

Software Mentioned

GraphPad Prism
GraphPad
MCID
BETA

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