Metformin improves ovarian follicle dynamics by reducing theca cell proliferation and CYP-17 expression in an androgenized rat model

Detalhes bibliográficos
Autor(a) principal: Mahamed, Roberta Rassi [UNIFESP]
Data de Publicação: 2018
Outros Autores: Maganhin, Carla Cristina, Sasso, Gisela Rodrigues Silva [UNIFESP], Simões, Manuel de Jesus [UNIFESP], Baracat, Maria Cândida Pinheiro [UNIFESP], Baracat, Edmund Chada [UNIFESP], Soares Junior, Jose Maria [UNIFESP]
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNIFESP
Texto Completo: https://repositorio.unifesp.br/handle/11600/55926
http://dx.doi.org/10.1186/s13048-018-0392-1
Resumo: Background: Metformin influences insulin receptor signaling, which might interfere with the proliferation of ovarian follicular structures and steroidogenesis. We hypothesize that reductions in glucose and insulin levels might interfere with CYP-17 expression and histomorphological changes in an androgenized rat model. The aim of this study was to analyze the effect of metformin on CYP-17 expression, follicular dynamics, and proliferative parameters in neonatally androgenized female rats. Methods: Thirty-six newborn rats were randomly allocated to the following three groups on the third day of life: control (CG, n = 12), androgenized (GA, n = 12), and androgenized + metformin (GAmet, n = 12). The GA and GAmet animals were administered 0.1 mL of testosterone propionate (1.25 mg/animal) diluted in castor oil (vehicle) in a single dose
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spelling Mahamed, Roberta Rassi [UNIFESP]Maganhin, Carla CristinaSasso, Gisela Rodrigues Silva [UNIFESP]Simões, Manuel de Jesus [UNIFESP]Baracat, Maria Cândida Pinheiro [UNIFESP]Baracat, Edmund Chada [UNIFESP]Soares Junior, Jose Maria [UNIFESP]2020-07-20T16:31:23Z2020-07-20T16:31:23Z2018Journal Of Ovarian Research. London, v. 11, p. -, 2018.1757-2215https://repositorio.unifesp.br/handle/11600/55926http://dx.doi.org/10.1186/s13048-018-0392-1WOS000426677200001.pdf10.1186/s13048-018-0392-1WOS:000426677200001Background: Metformin influences insulin receptor signaling, which might interfere with the proliferation of ovarian follicular structures and steroidogenesis. We hypothesize that reductions in glucose and insulin levels might interfere with CYP-17 expression and histomorphological changes in an androgenized rat model. The aim of this study was to analyze the effect of metformin on CYP-17 expression, follicular dynamics, and proliferative parameters in neonatally androgenized female rats. Methods: Thirty-six newborn rats were randomly allocated to the following three groups on the third day of life: control (CG, n = 12), androgenized (GA, n = 12), and androgenized + metformin (GAmet, n = 12). The GA and GAmet animals were administered 0.1 mL of testosterone propionate (1.25 mg/animal) diluted in castor oil (vehicle) in a single dosethe CG rats received a subcutaneous injection of the vehicle in the dorsum. After 90 days, gavage treatment was initiated, distilled water was administered to the CG and GA rats, and metformin (150 mg/kg) was administered to the GAmet animals. The treatment was administered daily for six weeks. Following anesthesia, blood was drawn for biochemical measurements, and the ovaries were removed for histological and immunohistochemical analyses of Ki67, VEGFA and CYP17 expression. The glucose and insulin levels were also measured. Results: The comparison of the GA and GAmet animals revealed that metformin decreased the weight as well as the glucose and insulin levels, slowed the proliferation of the theca interna and interstitial cells, as evidenced by Ki-67 and VEGF-A expression, and diminished CYP17 expression in the analyzed ovarian structures. In addition, metformin reduced the number of degenerating follicles and interstitial cells and improved angiogenesis. Conclusion: Metformin improves the carbohydrate metabolism, reduces proliferation, and decreases CYP-17 expression in the follicular structures of androgenized rats.Sao Paulo Research Foundation (FAPESP)Univ Fed Sao Paulo, Escola Paulista Med, Dept Gynecol, Sao Paulo, BrazilUniv Sao Paulo, Fac Med, Hosp Clin,Dept Obstet & Ginecol, Lab Mol & Struct Gynecol LIM 58,Disciplina Gineco, Ave Dr Arnaldo,455 Sala 2113, BR-01246903 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Escola Paulista Med, Dept Morphol & Genet, Sao Paulo, BrazilUniv Fed Sao Paulo, Escola Paulista Med, Dept Gynecol, Sao Paulo, BrazilUniv Fed Sao Paulo, Escola Paulista Med, Dept Morphol & Genet, Sao Paulo, BrazilFAPESP: 2009/54019-9Web of Science-engBiomed Central LtdJournal Of Ovarian ResearchMetforminSteroidogenesisOvaryRatMetformin improves ovarian follicle dynamics by reducing theca cell proliferation and CYP-17 expression in an androgenized rat modelinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleLondonv. 11info:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESPORIGINALWOS000426677200001.pdfapplication/pdf1504737${dspace.ui.url}/bitstream/11600/55926/1/WOS000426677200001.pdfbf41908c4cf8f79de4ba9a750c4856a5MD51open accessTEXTWOS000426677200001.pdf.txtWOS000426677200001.pdf.txtExtracted texttext/plain43499${dspace.ui.url}/bitstream/11600/55926/2/WOS000426677200001.pdf.txt761e70b1fe99b76e586c4bdc32ce8bfcMD52open accessTHUMBNAILWOS000426677200001.pdf.jpgWOS000426677200001.pdf.jpgIM Thumbnailimage/jpeg6763${dspace.ui.url}/bitstream/11600/55926/4/WOS000426677200001.pdf.jpgb120874ddcfce169d554138d215f6c8eMD54open access11600/559262022-08-01 01:50:16.052open accessoai:repositorio.unifesp.br:11600/55926Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652023-05-25T12:14:20.548565Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false
dc.title.en.fl_str_mv Metformin improves ovarian follicle dynamics by reducing theca cell proliferation and CYP-17 expression in an androgenized rat model
title Metformin improves ovarian follicle dynamics by reducing theca cell proliferation and CYP-17 expression in an androgenized rat model
spellingShingle Metformin improves ovarian follicle dynamics by reducing theca cell proliferation and CYP-17 expression in an androgenized rat model
Mahamed, Roberta Rassi [UNIFESP]
Metformin
Steroidogenesis
Ovary
Rat
title_short Metformin improves ovarian follicle dynamics by reducing theca cell proliferation and CYP-17 expression in an androgenized rat model
title_full Metformin improves ovarian follicle dynamics by reducing theca cell proliferation and CYP-17 expression in an androgenized rat model
title_fullStr Metformin improves ovarian follicle dynamics by reducing theca cell proliferation and CYP-17 expression in an androgenized rat model
title_full_unstemmed Metformin improves ovarian follicle dynamics by reducing theca cell proliferation and CYP-17 expression in an androgenized rat model
title_sort Metformin improves ovarian follicle dynamics by reducing theca cell proliferation and CYP-17 expression in an androgenized rat model
author Mahamed, Roberta Rassi [UNIFESP]
author_facet Mahamed, Roberta Rassi [UNIFESP]
Maganhin, Carla Cristina
Sasso, Gisela Rodrigues Silva [UNIFESP]
Simões, Manuel de Jesus [UNIFESP]
Baracat, Maria Cândida Pinheiro [UNIFESP]
Baracat, Edmund Chada [UNIFESP]
Soares Junior, Jose Maria [UNIFESP]
author_role author
author2 Maganhin, Carla Cristina
Sasso, Gisela Rodrigues Silva [UNIFESP]
Simões, Manuel de Jesus [UNIFESP]
Baracat, Maria Cândida Pinheiro [UNIFESP]
Baracat, Edmund Chada [UNIFESP]
Soares Junior, Jose Maria [UNIFESP]
author2_role author
author
author
author
author
author
dc.contributor.author.fl_str_mv Mahamed, Roberta Rassi [UNIFESP]
Maganhin, Carla Cristina
Sasso, Gisela Rodrigues Silva [UNIFESP]
Simões, Manuel de Jesus [UNIFESP]
Baracat, Maria Cândida Pinheiro [UNIFESP]
Baracat, Edmund Chada [UNIFESP]
Soares Junior, Jose Maria [UNIFESP]
dc.subject.eng.fl_str_mv Metformin
Steroidogenesis
Ovary
Rat
topic Metformin
Steroidogenesis
Ovary
Rat
description Background: Metformin influences insulin receptor signaling, which might interfere with the proliferation of ovarian follicular structures and steroidogenesis. We hypothesize that reductions in glucose and insulin levels might interfere with CYP-17 expression and histomorphological changes in an androgenized rat model. The aim of this study was to analyze the effect of metformin on CYP-17 expression, follicular dynamics, and proliferative parameters in neonatally androgenized female rats. Methods: Thirty-six newborn rats were randomly allocated to the following three groups on the third day of life: control (CG, n = 12), androgenized (GA, n = 12), and androgenized + metformin (GAmet, n = 12). The GA and GAmet animals were administered 0.1 mL of testosterone propionate (1.25 mg/animal) diluted in castor oil (vehicle) in a single dose
publishDate 2018
dc.date.issued.fl_str_mv 2018
dc.date.accessioned.fl_str_mv 2020-07-20T16:31:23Z
dc.date.available.fl_str_mv 2020-07-20T16:31:23Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv Journal Of Ovarian Research. London, v. 11, p. -, 2018.
dc.identifier.uri.fl_str_mv https://repositorio.unifesp.br/handle/11600/55926
http://dx.doi.org/10.1186/s13048-018-0392-1
dc.identifier.issn.none.fl_str_mv 1757-2215
dc.identifier.file.none.fl_str_mv WOS000426677200001.pdf
dc.identifier.doi.none.fl_str_mv 10.1186/s13048-018-0392-1
dc.identifier.wos.none.fl_str_mv WOS:000426677200001
identifier_str_mv Journal Of Ovarian Research. London, v. 11, p. -, 2018.
1757-2215
WOS000426677200001.pdf
10.1186/s13048-018-0392-1
WOS:000426677200001
url https://repositorio.unifesp.br/handle/11600/55926
http://dx.doi.org/10.1186/s13048-018-0392-1
dc.language.iso.fl_str_mv eng
language eng
dc.relation.ispartof.none.fl_str_mv Journal Of Ovarian Research
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv -
dc.coverage.none.fl_str_mv London
dc.publisher.none.fl_str_mv Biomed Central Ltd
publisher.none.fl_str_mv Biomed Central Ltd
dc.source.none.fl_str_mv reponame:Repositório Institucional da UNIFESP
instname:Universidade Federal de São Paulo (UNIFESP)
instacron:UNIFESP
instname_str Universidade Federal de São Paulo (UNIFESP)
instacron_str UNIFESP
institution UNIFESP
reponame_str Repositório Institucional da UNIFESP
collection Repositório Institucional da UNIFESP
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