Prenatal Sex Hormone Exposure Is Associated with the Development of Autism Spectrum Disorder

Int J Mol Sci. 2023 Jan 22;24(3):2203. doi: 10.3390/ijms24032203.

Abstract

Sexual differentiation is a major developmental process. Sex differences resulting from sexual differentiation have attracted the attention of researchers. Unraveling what contributes to and underlies sex differences will provide valuable insights into the development of neurodevelopmental disorders that exhibit sex biases. Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects an individual's social interaction and communication abilities, and its male preponderance has been consistently reported in clinical studies. The etiology of male preponderance remains unclear, but progress has been made in studying prenatal sex hormone exposure. The present review examined studies that focused on the association between prenatal testosterone exposure and ASD development, as well as sex-specific behaviors in individuals with ASD. This review also included studies on maternal immune activation-induced developmental abnormalities that also showed striking sex differences in offspring and discussed its possible interacting roles in ASD so as to present a potential approach for future studies on sex biases in ASD.

Keywords: androgen; autism spectrum disorder; development; extreme male brain; female protective effect; prenatal environment; sex bias; sex difference; sex hormone; testosterone.

Publication types

  • Review

MeSH terms

  • Autism Spectrum Disorder* / etiology
  • Causality
  • Female
  • Humans
  • Male
  • Neurodevelopmental Disorders* / complications
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Sex Characteristics
  • Testosterone

Substances

  • Testosterone

Grants and funding

This work was supported by the Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Scientific Research (C) (20K06872) to N.U., Uehara Memorial Foundation to N.U., Takeda Science Foundation to N.U., Mochida Memorial Foundation for Medical and Pharmaceutical Research to N.U., Osaka Medical Research Foundation for Intractable Diseases to N.U., and SENSHIN Medical Research Foundation to N.U.