Neonatal androgenization-induced early endocrine–metabolic and ovary misprogramming in the female rat

Autores
Ongaro Gambino, Luisina; Salvetti, Natalia Raquel; Giovambattista, Andres; Spinedi, Eduardo Julio; Ortega, Hugo Hector
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Aim: Androgen excess predisposes the organism to develop metabolic–endocrine and reproductive dysfunctions, among them the development of a phenotype resembling that of human Polycystic Ovary Syndrome (PCOS). Methods: We analyzed the impact of a single neonatal (5 day-old) testosterone propionate (TP; s.c. 1.25 mg/female pup) dose on: a) several metabolic–endocrine activities and b) ovarian steroidogenic and granulosa cell (GC) functions and also follicular population in juvenile and adult TP and control (CT) rats. Key findings: Compared to CT rats, TP animals were characterized by: a) accelerated growth, hyperadiposity and hyperleptinemia, b) very early (pre-weaning age) vaginal opening, c) hyperinsulinemia in adult life, d) dysfunctional ovarian steroidogenesis, e) conserved GC functionality in both juveniles (in vitro) and adults (in vivo), and f) estrous cycles arrested at estrus. Finally, histological studies of the ovaries indicated that in TP (vs. CT) rats: i) primary and antral follicle frequencies were 3- and 15-fold higher and lower, respectively, in juveniles and ii) secondary and atretic follicle frequencies were 3- and 5-fold lower and higher, respectively, in adults. Large cystic images without corpus luteum were observed in the ovaries from adult TP rats only. Significance: Our results strongly suggest that transient neonatal hyperandrogenemia induced early misprogramming of metabolic–endocrine and ovarian (steroidogenesis/folliculogenesis) functions. Conversely, TP rats preserved their ovary GC endocrine function. Our results further support the high risk of developing ovarian hyperstimulation syndrome for infertile women with transient/chronic hyperandrogenemia (PCOS) subjected to assisted reproductive technologies.
Fil: Ongaro Gambino, Luisina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Instituto Multidisciplinario de Biología Celular (i); Argentina. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; Argentina
Fil: Salvetti, Natalia Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe. Instituto de Ciencias Veterinarias del Litoral; Argentina
Fil: Giovambattista, Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico la Plata. Instituto Multidisciplinario de Biología Celular (i); Argentina. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; Argentina
Fil: Spinedi, Eduardo Julio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico la Plata. Centro de Endocrinologia Experimental y Aplicada (i); Argentina. Universidad Nacional de La Plata; Argentina
Fil: Ortega, Hugo Hector. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe. Instituto de Ciencias Veterinarias del Litoral; Argentina. Universidad Nacional del Litoral; Argentina
Materia
Adipose Tissue
Growth
Insulin
Leptin
Ovary
Steroidogenesis
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/10100
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/10100
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Neonatal androgenization-induced early endocrine–metabolic and ovary misprogramming in the female ratOngaro Gambino, LuisinaSalvetti, Natalia RaquelGiovambattista, AndresSpinedi, Eduardo JulioOrtega, Hugo HectorAdipose TissueGrowthInsulinLeptinOvarySteroidogenesishttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Aim: Androgen excess predisposes the organism to develop metabolic–endocrine and reproductive dysfunctions, among them the development of a phenotype resembling that of human Polycystic Ovary Syndrome (PCOS). Methods: We analyzed the impact of a single neonatal (5 day-old) testosterone propionate (TP; s.c. 1.25 mg/female pup) dose on: a) several metabolic–endocrine activities and b) ovarian steroidogenic and granulosa cell (GC) functions and also follicular population in juvenile and adult TP and control (CT) rats. Key findings: Compared to CT rats, TP animals were characterized by: a) accelerated growth, hyperadiposity and hyperleptinemia, b) very early (pre-weaning age) vaginal opening, c) hyperinsulinemia in adult life, d) dysfunctional ovarian steroidogenesis, e) conserved GC functionality in both juveniles (in vitro) and adults (in vivo), and f) estrous cycles arrested at estrus. Finally, histological studies of the ovaries indicated that in TP (vs. CT) rats: i) primary and antral follicle frequencies were 3- and 15-fold higher and lower, respectively, in juveniles and ii) secondary and atretic follicle frequencies were 3- and 5-fold lower and higher, respectively, in adults. Large cystic images without corpus luteum were observed in the ovaries from adult TP rats only. Significance: Our results strongly suggest that transient neonatal hyperandrogenemia induced early misprogramming of metabolic–endocrine and ovarian (steroidogenesis/folliculogenesis) functions. Conversely, TP rats preserved their ovary GC endocrine function. Our results further support the high risk of developing ovarian hyperstimulation syndrome for infertile women with transient/chronic hyperandrogenemia (PCOS) subjected to assisted reproductive technologies.Fil: Ongaro Gambino, Luisina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Instituto Multidisciplinario de Biología Celular (i); Argentina. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; ArgentinaFil: Salvetti, Natalia Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe. Instituto de Ciencias Veterinarias del Litoral; ArgentinaFil: Giovambattista, Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico la Plata. Instituto Multidisciplinario de Biología Celular (i); Argentina. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; ArgentinaFil: Spinedi, Eduardo Julio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico la Plata. Centro de Endocrinologia Experimental y Aplicada (i); Argentina. Universidad Nacional de La Plata; ArgentinaFil: Ortega, Hugo Hector. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe. Instituto de Ciencias Veterinarias del Litoral; Argentina. Universidad Nacional del Litoral; ArgentinaPergamon-elsevier Science Ltd2015-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/10100Ongaro Gambino, Luisina; Salvetti, Natalia Raquel; Giovambattista, Andres; Spinedi, Eduardo Julio; Ortega, Hugo Hector; Neonatal androgenization-induced early endocrine–metabolic and ovary misprogramming in the female rat; Pergamon-elsevier Science Ltd; Life Sciences; 130; 6-2015; 66-720024-3205enginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.lfs.2015.03.008info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:15:07Zoai:ri.conicet.gov.ar:11336/10100instacron: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 10:15:07.433CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Neonatal androgenization-induced early endocrine–metabolic and ovary misprogramming in the female rat
title Neonatal androgenization-induced early endocrine–metabolic and ovary misprogramming in the female rat
spellingShingle Neonatal androgenization-induced early endocrine–metabolic and ovary misprogramming in the female rat
Ongaro Gambino, Luisina
Adipose Tissue
Growth
Insulin
Leptin
Ovary
Steroidogenesis
title_short Neonatal androgenization-induced early endocrine–metabolic and ovary misprogramming in the female rat
title_full Neonatal androgenization-induced early endocrine–metabolic and ovary misprogramming in the female rat
title_fullStr Neonatal androgenization-induced early endocrine–metabolic and ovary misprogramming in the female rat
title_full_unstemmed Neonatal androgenization-induced early endocrine–metabolic and ovary misprogramming in the female rat
title_sort Neonatal androgenization-induced early endocrine–metabolic and ovary misprogramming in the female rat
dc.creator.none.fl_str_mv Ongaro Gambino, Luisina
Salvetti, Natalia Raquel
Giovambattista, Andres
Spinedi, Eduardo Julio
Ortega, Hugo Hector
author Ongaro Gambino, Luisina
author_facet Ongaro Gambino, Luisina
Salvetti, Natalia Raquel
Giovambattista, Andres
Spinedi, Eduardo Julio
Ortega, Hugo Hector
author_role author
author2 Salvetti, Natalia Raquel
Giovambattista, Andres
Spinedi, Eduardo Julio
Ortega, Hugo Hector
author2_role author
author
author
author
dc.subject.none.fl_str_mv Adipose Tissue
Growth
Insulin
Leptin
Ovary
Steroidogenesis
topic Adipose Tissue
Growth
Insulin
Leptin
Ovary
Steroidogenesis
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Aim: Androgen excess predisposes the organism to develop metabolic–endocrine and reproductive dysfunctions, among them the development of a phenotype resembling that of human Polycystic Ovary Syndrome (PCOS). Methods: We analyzed the impact of a single neonatal (5 day-old) testosterone propionate (TP; s.c. 1.25 mg/female pup) dose on: a) several metabolic–endocrine activities and b) ovarian steroidogenic and granulosa cell (GC) functions and also follicular population in juvenile and adult TP and control (CT) rats. Key findings: Compared to CT rats, TP animals were characterized by: a) accelerated growth, hyperadiposity and hyperleptinemia, b) very early (pre-weaning age) vaginal opening, c) hyperinsulinemia in adult life, d) dysfunctional ovarian steroidogenesis, e) conserved GC functionality in both juveniles (in vitro) and adults (in vivo), and f) estrous cycles arrested at estrus. Finally, histological studies of the ovaries indicated that in TP (vs. CT) rats: i) primary and antral follicle frequencies were 3- and 15-fold higher and lower, respectively, in juveniles and ii) secondary and atretic follicle frequencies were 3- and 5-fold lower and higher, respectively, in adults. Large cystic images without corpus luteum were observed in the ovaries from adult TP rats only. Significance: Our results strongly suggest that transient neonatal hyperandrogenemia induced early misprogramming of metabolic–endocrine and ovarian (steroidogenesis/folliculogenesis) functions. Conversely, TP rats preserved their ovary GC endocrine function. Our results further support the high risk of developing ovarian hyperstimulation syndrome for infertile women with transient/chronic hyperandrogenemia (PCOS) subjected to assisted reproductive technologies.
Fil: Ongaro Gambino, Luisina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Instituto Multidisciplinario de Biología Celular (i); Argentina. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; Argentina
Fil: Salvetti, Natalia Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe. Instituto de Ciencias Veterinarias del Litoral; Argentina
Fil: Giovambattista, Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico la Plata. Instituto Multidisciplinario de Biología Celular (i); Argentina. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; Argentina
Fil: Spinedi, Eduardo Julio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico la Plata. Centro de Endocrinologia Experimental y Aplicada (i); Argentina. Universidad Nacional de La Plata; Argentina
Fil: Ortega, Hugo Hector. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe. Instituto de Ciencias Veterinarias del Litoral; Argentina. Universidad Nacional del Litoral; Argentina
description Aim: Androgen excess predisposes the organism to develop metabolic–endocrine and reproductive dysfunctions, among them the development of a phenotype resembling that of human Polycystic Ovary Syndrome (PCOS). Methods: We analyzed the impact of a single neonatal (5 day-old) testosterone propionate (TP; s.c. 1.25 mg/female pup) dose on: a) several metabolic–endocrine activities and b) ovarian steroidogenic and granulosa cell (GC) functions and also follicular population in juvenile and adult TP and control (CT) rats. Key findings: Compared to CT rats, TP animals were characterized by: a) accelerated growth, hyperadiposity and hyperleptinemia, b) very early (pre-weaning age) vaginal opening, c) hyperinsulinemia in adult life, d) dysfunctional ovarian steroidogenesis, e) conserved GC functionality in both juveniles (in vitro) and adults (in vivo), and f) estrous cycles arrested at estrus. Finally, histological studies of the ovaries indicated that in TP (vs. CT) rats: i) primary and antral follicle frequencies were 3- and 15-fold higher and lower, respectively, in juveniles and ii) secondary and atretic follicle frequencies were 3- and 5-fold lower and higher, respectively, in adults. Large cystic images without corpus luteum were observed in the ovaries from adult TP rats only. Significance: Our results strongly suggest that transient neonatal hyperandrogenemia induced early misprogramming of metabolic–endocrine and ovarian (steroidogenesis/folliculogenesis) functions. Conversely, TP rats preserved their ovary GC endocrine function. Our results further support the high risk of developing ovarian hyperstimulation syndrome for infertile women with transient/chronic hyperandrogenemia (PCOS) subjected to assisted reproductive technologies.
publishDate 2015
dc.date.none.fl_str_mv 2015-06
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/11336/10100
Ongaro Gambino, Luisina; Salvetti, Natalia Raquel; Giovambattista, Andres; Spinedi, Eduardo Julio; Ortega, Hugo Hector; Neonatal androgenization-induced early endocrine–metabolic and ovary misprogramming in the female rat; Pergamon-elsevier Science Ltd; Life Sciences; 130; 6-2015; 66-72
0024-3205
url http://hdl.handle.net/11336/10100
identifier_str_mv Ongaro Gambino, Luisina; Salvetti, Natalia Raquel; Giovambattista, Andres; Spinedi, Eduardo Julio; Ortega, Hugo Hector; Neonatal androgenization-induced early endocrine–metabolic and ovary misprogramming in the female rat; Pergamon-elsevier Science Ltd; Life Sciences; 130; 6-2015; 66-72
0024-3205
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.lfs.2015.03.008
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
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Pergamon-elsevier Science Ltd
publisher.none.fl_str_mv Pergamon-elsevier Science Ltd
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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score 13.070432

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