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

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dc.citation.volumev. 11
dc.contributor.authorMahamed, Roberta Rassi [UNIFESP]
dc.contributor.authorMaganhin, Carla Cristina
dc.contributor.authorSasso, Gisela Rodrigues Silva [UNIFESP]
dc.contributor.authorSimões, Manuel de Jesus [UNIFESP]
dc.contributor.authorBaracat, Maria Cândida Pinheiro [UNIFESP]
dc.contributor.authorBaracat, Edmund Chada [UNIFESP]
dc.contributor.authorSoares Junior, Jose Maria [UNIFESP]
dc.coverageLondon
dc.date.accessioned2020-07-20T16:31:23Z
dc.date.available2020-07-20T16:31:23Z
dc.date.issued2018
dc.description.abstractBackground: 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 doseen
dc.description.abstractthe 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.en
dc.description.affiliationUniv Fed Sao Paulo, Escola Paulista Med, Dept Gynecol, Sao Paulo, Brazil
dc.description.affiliationUniv 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, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Escola Paulista Med, Dept Morphol & Genet, Sao Paulo, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Escola Paulista Med, Dept Gynecol, Sao Paulo, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Escola Paulista Med, Dept Morphol & Genet, Sao Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipSao Paulo Research Foundation (FAPESP)
dc.description.sponsorshipIDFAPESP: 2009/54019-9
dc.format.extent-
dc.identifierhttp://dx.doi.org/10.1186/s13048-018-0392-1
dc.identifier.citationJournal Of Ovarian Research. London, v. 11, p. -, 2018.
dc.identifier.doi10.1186/s13048-018-0392-1
dc.identifier.fileWOS000426677200001.pdf
dc.identifier.issn1757-2215
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/55926
dc.identifier.wosWOS:000426677200001
dc.language.isoeng
dc.publisherBiomed Central Ltd
dc.relation.ispartofJournal Of Ovarian Research
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectMetforminen
dc.subjectSteroidogenesisen
dc.subjectOvaryen
dc.subjectRaten
dc.titleMetformin improves ovarian follicle dynamics by reducing theca cell proliferation and CYP-17 expression in an androgenized rat modelen
dc.typeinfo:eu-repo/semantics/article
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