Neonatal inhibition of DNA methylation disrupts testosterone-dependent masculinization of neurochemical phenotype
- Autores
- Cisternas, Carla Daniela; Cortese, Maria Laura; Golynker, Ilona; Castillo-Ruiz, Alexandra; Forger, Nancy G.
- Año de publicación
- 2020
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Many neural sex differences are differences in the number of neurons of a particular phenotype. For example, male rodents have more calbindin-expressing neurons in the medial preoptic area (mPOA) and bed nucleus of the stria terminalis (BNST), and females have more neurons expressing estrogen receptor alpha (ERα) and kisspeptin in the ventromedial nucleus of the hypothalamus (VMH) and the anteroventral periventricular nucleus (AVPV), respectively. These sex differences depend on neonatal exposure to testosterone, but the underlying molecular mechanisms are unknown. DNA methylation is important for cell phenotype differentiation throughout the developing organism. We hypothesized that testosterone causes sex differences in neurochemical phenotype via changes in DNA methylation, and tested this by inhibiting DNA methylation neonatally in male and female mice, and in females given a masculinizing dose of testosterone. Neonatal testosterone treatment masculinized calbindin, ERα and kisspeptin cell number of females at weaning. Inhibiting DNA methylation with zebularine increased calbindin cell number only in control females, thus eliminating sex differences in calbindin in the mPOA and BNST. Zebularine also reduced the sex difference in ERα cell number in the VMH, in this case by increasing ERα neuron number in males and testosterone-treated females. In contrast, the neonatal inhibition of DNA methylation had no effect on kisspeptin cell number. We conclude that testosterone normally increases the number of calbindin cells and reduces ERα cells in males through orchestrated changes in DNA methylation, contributing to, or causing, the sex differences in both cell types.
Fil: Cisternas, Carla Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina
Fil: Cortese, Maria Laura. Georgia State University; Estados Unidos
Fil: Golynker, Ilona. Georgia State University; Estados Unidos
Fil: Castillo-Ruiz, Alexandra. Georgia State University; Estados Unidos
Fil: Forger, Nancy G.. Georgia State University; Estados Unidos - Materia
-
ANTEROVENTRAL PERIVENTRICULAR NUCLEUS
BED NUCLEUS OF THE STRIA TERMINALIS
EPIGENETIC
MEDIAL PREOPTIC AREA
SEX DIFFERENCE - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/129380
Ver los metadatos del registro completo
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CONICET Digital (CONICET) |
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Neonatal inhibition of DNA methylation disrupts testosterone-dependent masculinization of neurochemical phenotypeCisternas, Carla DanielaCortese, Maria LauraGolynker, IlonaCastillo-Ruiz, AlexandraForger, Nancy G.ANTEROVENTRAL PERIVENTRICULAR NUCLEUSBED NUCLEUS OF THE STRIA TERMINALISEPIGENETICMEDIAL PREOPTIC AREASEX DIFFERENCEhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Many neural sex differences are differences in the number of neurons of a particular phenotype. For example, male rodents have more calbindin-expressing neurons in the medial preoptic area (mPOA) and bed nucleus of the stria terminalis (BNST), and females have more neurons expressing estrogen receptor alpha (ERα) and kisspeptin in the ventromedial nucleus of the hypothalamus (VMH) and the anteroventral periventricular nucleus (AVPV), respectively. These sex differences depend on neonatal exposure to testosterone, but the underlying molecular mechanisms are unknown. DNA methylation is important for cell phenotype differentiation throughout the developing organism. We hypothesized that testosterone causes sex differences in neurochemical phenotype via changes in DNA methylation, and tested this by inhibiting DNA methylation neonatally in male and female mice, and in females given a masculinizing dose of testosterone. Neonatal testosterone treatment masculinized calbindin, ERα and kisspeptin cell number of females at weaning. Inhibiting DNA methylation with zebularine increased calbindin cell number only in control females, thus eliminating sex differences in calbindin in the mPOA and BNST. Zebularine also reduced the sex difference in ERα cell number in the VMH, in this case by increasing ERα neuron number in males and testosterone-treated females. In contrast, the neonatal inhibition of DNA methylation had no effect on kisspeptin cell number. We conclude that testosterone normally increases the number of calbindin cells and reduces ERα cells in males through orchestrated changes in DNA methylation, contributing to, or causing, the sex differences in both cell types.Fil: Cisternas, Carla Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Cortese, Maria Laura. Georgia State University; Estados UnidosFil: Golynker, Ilona. Georgia State University; Estados UnidosFil: Castillo-Ruiz, Alexandra. Georgia State University; Estados UnidosFil: Forger, Nancy G.. Georgia State University; Estados UnidosEndocrine Society2020-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/129380Cisternas, Carla Daniela; Cortese, Maria Laura; Golynker, Ilona; Castillo-Ruiz, Alexandra; Forger, Nancy G.; Neonatal inhibition of DNA methylation disrupts testosterone-dependent masculinization of neurochemical phenotype; Endocrine Society; Endocrinology; 161; 1; 1-2020; 1-270013-72271945-7170CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/endo/advance-article/doi/10.1210/endocr/bqz022/5631853info:eu-repo/semantics/altIdentifier/doi/10.1210/endocr/bqz022info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:39:47Zoai:ri.conicet.gov.ar:11336/129380instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:39:48.004CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Neonatal inhibition of DNA methylation disrupts testosterone-dependent masculinization of neurochemical phenotype |
title |
Neonatal inhibition of DNA methylation disrupts testosterone-dependent masculinization of neurochemical phenotype |
spellingShingle |
Neonatal inhibition of DNA methylation disrupts testosterone-dependent masculinization of neurochemical phenotype Cisternas, Carla Daniela ANTEROVENTRAL PERIVENTRICULAR NUCLEUS BED NUCLEUS OF THE STRIA TERMINALIS EPIGENETIC MEDIAL PREOPTIC AREA SEX DIFFERENCE |
title_short |
Neonatal inhibition of DNA methylation disrupts testosterone-dependent masculinization of neurochemical phenotype |
title_full |
Neonatal inhibition of DNA methylation disrupts testosterone-dependent masculinization of neurochemical phenotype |
title_fullStr |
Neonatal inhibition of DNA methylation disrupts testosterone-dependent masculinization of neurochemical phenotype |
title_full_unstemmed |
Neonatal inhibition of DNA methylation disrupts testosterone-dependent masculinization of neurochemical phenotype |
title_sort |
Neonatal inhibition of DNA methylation disrupts testosterone-dependent masculinization of neurochemical phenotype |
dc.creator.none.fl_str_mv |
Cisternas, Carla Daniela Cortese, Maria Laura Golynker, Ilona Castillo-Ruiz, Alexandra Forger, Nancy G. |
author |
Cisternas, Carla Daniela |
author_facet |
Cisternas, Carla Daniela Cortese, Maria Laura Golynker, Ilona Castillo-Ruiz, Alexandra Forger, Nancy G. |
author_role |
author |
author2 |
Cortese, Maria Laura Golynker, Ilona Castillo-Ruiz, Alexandra Forger, Nancy G. |
author2_role |
author author author author |
dc.subject.none.fl_str_mv |
ANTEROVENTRAL PERIVENTRICULAR NUCLEUS BED NUCLEUS OF THE STRIA TERMINALIS EPIGENETIC MEDIAL PREOPTIC AREA SEX DIFFERENCE |
topic |
ANTEROVENTRAL PERIVENTRICULAR NUCLEUS BED NUCLEUS OF THE STRIA TERMINALIS EPIGENETIC MEDIAL PREOPTIC AREA SEX DIFFERENCE |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
dc.description.none.fl_txt_mv |
Many neural sex differences are differences in the number of neurons of a particular phenotype. For example, male rodents have more calbindin-expressing neurons in the medial preoptic area (mPOA) and bed nucleus of the stria terminalis (BNST), and females have more neurons expressing estrogen receptor alpha (ERα) and kisspeptin in the ventromedial nucleus of the hypothalamus (VMH) and the anteroventral periventricular nucleus (AVPV), respectively. These sex differences depend on neonatal exposure to testosterone, but the underlying molecular mechanisms are unknown. DNA methylation is important for cell phenotype differentiation throughout the developing organism. We hypothesized that testosterone causes sex differences in neurochemical phenotype via changes in DNA methylation, and tested this by inhibiting DNA methylation neonatally in male and female mice, and in females given a masculinizing dose of testosterone. Neonatal testosterone treatment masculinized calbindin, ERα and kisspeptin cell number of females at weaning. Inhibiting DNA methylation with zebularine increased calbindin cell number only in control females, thus eliminating sex differences in calbindin in the mPOA and BNST. Zebularine also reduced the sex difference in ERα cell number in the VMH, in this case by increasing ERα neuron number in males and testosterone-treated females. In contrast, the neonatal inhibition of DNA methylation had no effect on kisspeptin cell number. We conclude that testosterone normally increases the number of calbindin cells and reduces ERα cells in males through orchestrated changes in DNA methylation, contributing to, or causing, the sex differences in both cell types. Fil: Cisternas, Carla Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina Fil: Cortese, Maria Laura. Georgia State University; Estados Unidos Fil: Golynker, Ilona. Georgia State University; Estados Unidos Fil: Castillo-Ruiz, Alexandra. Georgia State University; Estados Unidos Fil: Forger, Nancy G.. Georgia State University; Estados Unidos |
description |
Many neural sex differences are differences in the number of neurons of a particular phenotype. For example, male rodents have more calbindin-expressing neurons in the medial preoptic area (mPOA) and bed nucleus of the stria terminalis (BNST), and females have more neurons expressing estrogen receptor alpha (ERα) and kisspeptin in the ventromedial nucleus of the hypothalamus (VMH) and the anteroventral periventricular nucleus (AVPV), respectively. These sex differences depend on neonatal exposure to testosterone, but the underlying molecular mechanisms are unknown. DNA methylation is important for cell phenotype differentiation throughout the developing organism. We hypothesized that testosterone causes sex differences in neurochemical phenotype via changes in DNA methylation, and tested this by inhibiting DNA methylation neonatally in male and female mice, and in females given a masculinizing dose of testosterone. Neonatal testosterone treatment masculinized calbindin, ERα and kisspeptin cell number of females at weaning. Inhibiting DNA methylation with zebularine increased calbindin cell number only in control females, thus eliminating sex differences in calbindin in the mPOA and BNST. Zebularine also reduced the sex difference in ERα cell number in the VMH, in this case by increasing ERα neuron number in males and testosterone-treated females. In contrast, the neonatal inhibition of DNA methylation had no effect on kisspeptin cell number. We conclude that testosterone normally increases the number of calbindin cells and reduces ERα cells in males through orchestrated changes in DNA methylation, contributing to, or causing, the sex differences in both cell types. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020-01 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
format |
article |
status_str |
publishedVersion |
dc.identifier.none.fl_str_mv |
http://hdl.handle.net/11336/129380 Cisternas, Carla Daniela; Cortese, Maria Laura; Golynker, Ilona; Castillo-Ruiz, Alexandra; Forger, Nancy G.; Neonatal inhibition of DNA methylation disrupts testosterone-dependent masculinization of neurochemical phenotype; Endocrine Society; Endocrinology; 161; 1; 1-2020; 1-27 0013-7227 1945-7170 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/129380 |
identifier_str_mv |
Cisternas, Carla Daniela; Cortese, Maria Laura; Golynker, Ilona; Castillo-Ruiz, Alexandra; Forger, Nancy G.; Neonatal inhibition of DNA methylation disrupts testosterone-dependent masculinization of neurochemical phenotype; Endocrine Society; Endocrinology; 161; 1; 1-2020; 1-27 0013-7227 1945-7170 CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/endo/advance-article/doi/10.1210/endocr/bqz022/5631853 info:eu-repo/semantics/altIdentifier/doi/10.1210/endocr/bqz022 |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
dc.format.none.fl_str_mv |
application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
Endocrine Society |
publisher.none.fl_str_mv |
Endocrine Society |
dc.source.none.fl_str_mv |
reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
reponame_str |
CONICET Digital (CONICET) |
collection |
CONICET Digital (CONICET) |
instname_str |
Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.name.fl_str_mv |
CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.mail.fl_str_mv |
dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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1844613259092557824 |
score |
13.070432 |