The role of apoptosis in sexual differentiation of the rat sexually dimorphic nucleus of the preoptic area
Abstract
The sexually dimorphic nucleus of the preoptic area (SDN-POA) in the rat hypothalamus is larger in volume in males than in females due to a larger number of cells in the nucleus. Although the SDN-POA, and its development, have been extensively studied, the actual mechanism of its sexual differentiation has not been established. The results of previous studies have not supported a role for gonadal steroids in the regulation of neurogenesis or the determination of the migratory pathway perinatally. In this study, the role of cell death in the development of the sexual dimorphism in the SDN-POA was investigated using in situ end-labeling to visualize fragmented DNA in apoptotic cells. In the experiments described here, the incidence of apoptosis was determined in part of the SDN-POA, the central division of the medial preoptic nucleus (MPNc), over the first 13 days postnatally in male and female rats. There was a sex difference in the incidence of apoptosis in the MPNc between postnatal days 7 and 10; the incidence was higher in females. The role of testosterone (T) in regulating the incidence of apoptosis in the developing MPNc was examined in neonatally castrated males following T or vehicle injection. Testosterone had a profound inhibitory effect on the incidence of apoptosis between days 6 and 10. In a control region within the lateral preoptic area, there was no sex difference in the incidence of apoptosis, nor was there an effect of T. Thus, the data indicate that the regu…
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Aromatization of testosterone to estrogen triggers neurite growth and neuronal plasticity in sexually dimorphic brain regions, including the sexually dimorphic nucleus of the rat pre-optic area.
“Also, aromatization of testosterone into estrogen is known to trigger neurite growth and neuronal plasticity in sexually dimorphic brain regions, including the sexually dimorphic nucleus of the rat pre-optic area (Davis, Popper, & Gorski, 1996; Davis, Shryne, & Gorski, 1996).”
From Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity (2017) · cites this paper as Davis, Popper, & Gorski, 1996
In rodents, many important and irreversible sex hormone-mediated effects on brain development are complete by postnatal day 10.
“In rodents, many important and irreversible sex hormone-mediated effects on brain development are complete by postnatal day 10 (Davis et al., 1996; McCarthy et al., 2017).”
From Excess Neonatal Testosterone Causes Male-Specific Social and Fear Memory Deficits in Wild-Type Mice (2025) · cites this paper as Davis et al., 1996
In rodents, postnatal day 18 is outside the critical period of sex-specific brain masculinization.
“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.”
From Excess Neonatal Testosterone Causes Male-Specific Social and Fear Memory Deficits in Wild-Type Mice (2025) · cites this paper as Davis et al., 1996
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“Pregnant rats were exposed to one of four treatments, administered via intraperitoneal injections, on E16 and E18, the beginning of the period of brain sexual differentiation (Davis et al., 1996; Jacobson et al., 1980).”
InfluentialExcess Neonatal Testosterone Causes Male-Specific Social and Fear Memory Deficits in Wild-Type Mice
Quiñones-Labernik, P., Blocklinger, K. L., Bruce, M. R., Hagan, E., Preuschl, D., Tesar, C., & Ferri, S. L. (2025) · eneuro · doi:10.1523/eneuro.0020-25.2025 · Cited by 4 · see citing works
“In rodents, sex hormone-mediated effects on brain development are complete by Postnatal Day (PN)10 (Davis et al., 1996; McCarthy et al., 2018).”
Influential
- Authors
- Davis, E. C., Popper, P., & Gorski, R. A.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Gorski, Roger A.
- ORCID
- Davis, Elise C.
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 1996-09
- Volume
- 734
- Issue
- 1-2
- Pages
- 10-18
- ISSN
- 0006-8993 (ISSN-L)
- OpenAlex
- W2042549272
- Cited by
- 330
- References
- 0
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 4 · 2023: 10 · 2022: 4 · 2021: 6 · 2020: 7 · 2019: 8 · 2018: 9 · 2017: 13 · 2016: 10 · 2015: 11 · 2014: 12 · 2013: 18 · 2012: 6
- FWCI
- 4.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD-01182, HD-07228, T32HD007228)
- 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
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- apoptosis, sexual differentiation, sexually dimorphic nucleus, preoptic area, medial preoptic nucleus, testosterone, postnatal development, sex differences, cell death, hypothalamus, neonatal castration
- MeSH terms
- Animals, Animals, Newborn, Cell Count, Female, Male, Orchiectomy, Preoptic Area, Reference Values, Sex Characteristics, Sex Differentiation, Testosterone, Rats, Sprague-Dawley, Apoptosis, Rats, DNA Fragmentation
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