Journal article
Excess neonatal testosterone causes male-specific social and fear memory deficits in wild-type mice
eNeuro, Vol.12(8), pp.ENEURO.0020-25.2025
08/2025
DOI: 10.1523/ENEURO.0020-25.2025
PMCID: PMC12320760
PMID: 40623833
Abstract
Neurodevelopmental disorders disproportionately affect males compared to females. The biological mechanisms of this male susceptibility or female protection have not been identified. There is evidence that fetal/neonatal gonadal hormones, which play a pivotal role in many aspects of development, may contribute. Here, we investigate the effects of excess testosterone during a critical period of sex-specific brain organization on social approach and fear learning behaviors in C57BL/6J wild-type mice. Male, but not female, mice treated with testosterone on the day of birth (postnatal day 0; PN0) exhibited decreased social approach as juveniles and decreased contextual fear memory as adults, compared to vehicle-treated controls. These deficits were not driven by anxiety-like behavior or changes in locomotion or body weight. Mice treated with the same dose of testosterone on postnatal day 18 (PN18), which is outside of the critical period of brain masculinization, did not demonstrate impairments compared to the vehicle group. These findings indicate that excess testosterone during a critical period of early development, but not shortly after, induces long-term deficits relevant to the male sex bias in neurodevelopmental disorders.
Excess testosterone during a critical period of sex-specific brain organization, results in male-specific social and cognitive deficits in mice while testosterone treatment outside of this developmental window did not alter behavior. This time-sensitive, brief hormonal dysregulation induces long-term changes, and may be involved in the male sex bias in neurodevelopmental disorders.
Details
- Title: Subtitle
- Excess neonatal testosterone causes male-specific social and fear memory deficits in wild-type mice
- Creators
- Pravda Quiñones-Labernik - University of IowaKelsey L Blocklinger - University of IowaMatthew R Bruce - Temple UniversityEmily Hagan - Department of Neuroscience and Pharmacology, University of Iowa, Iowa City, IA, 52242, United StatesDanielle Preuschl - University of Iowa, Stead Family Department of PediatricsCharlotte Tesar - Department of Pediatrics, University of Iowa, Iowa City, IA, 52242, United StatesSarah L Ferri - University of Iowa
- Resource Type
- Journal article
- Publication Details
- eNeuro, Vol.12(8), pp.ENEURO.0020-25.2025
- DOI
- 10.1523/ENEURO.0020-25.2025
- PMID
- 40623833
- PMCID
- PMC12320760
- NLM abbreviation
- eNeuro
- ISSN
- 2373-2822
- eISSN
- 2373-2822
- Publisher
- SOC NEUROSCIENCE
- Grant note
- National Institutes of Health: K01 MH119540, T32GM144636 University of Iowa Hawkeye Intellectual and Developmental Disabilities Research CenterNICHD: P50 HD103556 Neural Circuits and Behavior Core at the University of Iowa
This work was supported by the National Institutes of Health Grants K01 MH119540 (to S.L.F.) and T32GM144636 (to P.Q.-L.) and University of Iowa Hawkeye Intellectual and Developmental Disabilities Research Center (Hawk-IDDRC; NICHD; P50 HD103556; PI Abel and Strathearn; subaward to S.L.F.) . We thank Dr. Shane Heiney and the Neural Circuits and Behavior Core at the University of Iowa for their support.
- Language
- English
- Electronic publication date
- 07/07/2025
- Date published
- 08/2025
- Academic Unit
- Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Developmental and Behavioral Pediatrics; Neuroscience and Pharmacology
- Record Identifier
- 9984848020202771
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