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

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

Author Mahamed, Roberta Rassi Autor UNIFESP Google Scholar
Maganhin, Carla Cristina Google Scholar
Sasso, Gisela Rodrigues Silva Autor UNIFESP Google Scholar
Simões, Manuel de Jesus Autor UNIFESP Google Scholar
Baracat, Maria Cândida Pinheiro Autor UNIFESP Google Scholar
Baracat, Edmund Chada Autor UNIFESP Google Scholar
Soares Junior, Jose Maria Autor UNIFESP Google Scholar
Abstract 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

the 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.
Keywords Metformin
Steroidogenesis
Ovary
Rat
xmlui.dri2xhtml.METS-1.0.item-coverage London
Language English
Sponsor Sao Paulo Research Foundation (FAPESP)
Grant number FAPESP: 2009/54019-9
Date 2018
Published in Journal Of Ovarian Research. London, v. 11, p. -, 2018.
ISSN 1757-2215 (Sherpa/Romeo, impact factor)
Publisher Biomed Central Ltd
Extent -
Origin http://dx.doi.org/10.1186/s13048-018-0392-1
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000426677200001
URI https://repositorio.unifesp.br/handle/11600/55926

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