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Antenatal Glucocorticoid Exposure Results in Sex-Specific and Transgenerational Changes in Prefrontal Cortex Gene

Andrea Constantinof1, Vasilis G Moisiadis1, Alisa Kostaki1

  • 1Departments of Physiology, University of Toronto, Toronto, ON, M5S1A8, Canada.

Scientific Reports
|January 26, 2019
PubMed

Insights

Antenatal exposure to synthetic glucocorticoids (sGC) alters gene expression in the developing prefrontal cortex (PFC). These changes are sex-specific, persist across generations, and are linked to behavioral modifications in offspring.

Area of Science:

  • Neuroscience
  • Developmental Biology
  • Pharmacology

Background:

  • Synthetic glucocorticoids (sGC) are given to pregnant women to prevent preterm birth complications.
  • The prefrontal cortex (PFC) is crucial for stress regulation and behavior, expressing glucocorticoid receptors (GR).
  • Antenatal sGC exposure can lead to hyperactivity in offspring across multiple generations.

Purpose of the Study:

  • To investigate how antenatal sGC exposure modifies gene expression in the PFC.
  • To determine if these gene expression changes are sex-specific and transgenerational.
  • To link affected gene sets to observed behavioral alterations, specifically locomotor activity.

Main Methods:

  • RNA sequencing was performed on the PFC of F1 (male and female) and F2/F3 (female) offspring from the paternal lineage.
  • Regression modeling was used to correlate gene expression patterns with behavioral data.
  • Focus on sex-specific and generation-specific gene expression changes.

Main Results:

  • Antenatal sGC exposure induced significant sex-specific and generation-specific alterations in PFC gene expression.
  • Expression levels of four specific genes (C9orf116, Calb1, Glra3, Gpr52) were found to explain 20-29% of the variance in locomotor activity.
  • The study identified a link between sGC-induced gene expression changes and behavioral phenotypes.

Conclusions:

  • Antenatal sGC exposure has profound, long-lasting effects on the developing PFC.
  • These effects are transmitted across multiple generations, influencing offspring behavior.
  • The identified genes may be key mediators of sGC-induced behavioral changes, highlighting potential targets for future research.

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