Effects of chromosomal sex and hormonal influences on shaping sex differences in brain and behavior: Lessons from cases of disorders of sex development
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Sex differences in brain development and postnatal behavior are determined largely by genetic sex and in utero gonadal hormone secretions. In humans however, determining the weight that each of these factors contributes remains a challenge because social influences should also be considered. Cases of disorders of sex development (DSD) provide unique insight into how mutations in genes responsible for gonadal formation can perturb the subsequent developmental hormonal milieu and elicit changes in normal human brain maturation. Specific forms of DSDs such as complete androgen insensitivity syndrome (CAIS), congenital adrenal hyperplasia (CAH), and 5α‐reductase deficiency syndrome have variable effects between males and females, and the developmental outcomes of such conditions are largely dependent on sex chromosome composition. Medical and psychological works focused on CAH, CAIS, and 5α‐reductase deficiency have helped form the foundation for understanding the roles of genetic and hormonal factors necessary for guiding human brain development. Here we highlight how the three aforementioned DSDs contribute to brain and behavioral phenotypes that can uniquely affect 46,XY and 46,XX individuals in dramatically different fashions. © 2016 Wiley Periodicals, Inc.
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Sex determination is led by genes on sex chromosomes and release of sex hormones, especially androgens and estrogens, primarily from gonads, exerting effects on body, brain, and behavior.
“This process is led by genes located on the sex chromosomes and the release of sex hormones, especially androgens and estrogens, coming primarily from the gonads and exerting effects on the body, brain, and behavior [10–13].”
From Sex chromosomes and sex hormones differently shape microglial properties during normal physiological conditions in the adult mouse hippocampus (2025) · cites this paper as [11]
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- Authors
- Bramble, M. S., Lipson, A., Vashist, N., & Vilain, E.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Vilain, Eric
- Venue
- Journal of Neuroscience Research
- Publisher
- Wiley
- Published
- 2016-11-07
- Volume
- 95
- Issue
- 1-2
- Pages
- 65-74
- ISSN
- 0360-4012 (ISSN-L)
- 1097-4547
- PMC
- PMC7301881
- OpenAlex
- W2550808969
- Cited by
- 42
- References
- 77
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 2 · 2023: 11 · 2022: 4 · 2020: 5 · 2019: 1 · 2018: 6 · 2017: 4 · 2015: 1
- FWCI
- 0.33
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Neuroscience Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD068138)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Keywords
- disorders of sex development, sex differences in brain development, brain-behavior relationship, androgen insensitivity syndrome, congenital adrenal hyperplasia, 5-alpha-reductase deficiency, gonadal hormones, 46,XY disorders of sex development, 46,XX disorders, brain maturation, behavioral phenotypes
- MeSH terms
- Brain, Female, Humans, Male, Sex Characteristics, Sex Chromosomes, Disorders of Sex Development, Gonadal Steroid Hormones
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