Frontiers in neuroendocrinology

RORA’s role as a sex-specific molecular link in autism from gene regulation to symptoms across life

Updated

Abstract

RORA is frequently downregulated in autism spectrum disorder (ASD), impacting several critical biological pathways.

  • RORA integrates various biological processes, including hormone signaling, gene regulation, and immune function.
  • Its downregulation in ASD is linked to disrupted pathways that affect brain development and synapse formation.
  • Androgens suppress RORA expression, while estrogens activate it, which may explain the gender differences in ASD prevalence.
  • A feedback loop involving RORA and aromatase promotes androgen dominance and decreases estrogen-related protective effects.
  • RORA deficiency could lead to developmental issues in pregnancy, metabolic abnormalities in childhood, and inflammation-related symptoms.

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