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

Majid Iqbal1, Vasilis G Moisiadis, Alisa Kostaki

  • 1Department of Physiology, Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8.

Endocrinology
|May 9, 2012
PubMed

Insights

Prenatal synthetic glucocorticoid (sGC) exposure alters hypothalamic-pituitary-adrenal (HPA) axis function and behavior in second-generation offspring. These effects suggest long-term impacts on stress response and hormonal regulation across generations.

Area of Science:

  • Endocrinology
  • Developmental Biology
  • Neuroscience

Background:

  • Synthetic glucocorticoids (sGC) are used to promote fetal lung development in pregnancies at risk of preterm delivery.
  • Prenatal sGC exposure has been shown to affect hypothalamic-pituitary-adrenal (HPA) axis function in first-generation (F(1)) offspring.

Purpose of the Study:

  • To investigate whether prenatal sGC exposure impacts HPA function and behavior in the subsequent (F(2)) generation.
  • To assess the long-term consequences of maternal sGC treatment on offspring HPA axis regulation and behavior.

Main Methods:

  • Pregnant guinea pigs (F(0)) were administered betamethasone (BETA) or saline during gestation.
  • F(1) females were mated to produce F(2) offspring, whose HPA function and behavior were assessed.
  • HPA axis function was evaluated through stress responses and dexamethasone suppression tests.
  • Gene expression analysis of HPA-related components was performed in adult F(2) offspring.

Main Results:

  • F(2) offspring exposed prenatally to BETA exhibited reduced locomotor activity (males) and blunted cortisol responses to stress.
  • Differential effects on negative feedback regulation were observed in F(2) males and females following dexamethasone challenge.
  • F(2) BETA females showed reduced pituitary proopiomelanocortin and corticotropin-releasing hormone receptor expression.
  • Altered hippocampal glucocorticoid receptor expression was noted in both F(2) BETA males and females.

Conclusions:

  • Prenatal betamethasone treatment has lasting effects on HPA axis function and behavior in F(2) offspring.
  • Pituitary function is primarily affected in F(2) females, while hippocampal feedback systems are altered in both sexes.
  • These findings highlight potential transgenerational impacts of synthetic glucocorticoid therapy used in preterm labor management.

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