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

Autor(es)

Mahamed, Roberta Rassi ^{[1, 2]} ; Maganhin, Carla Cristina ^[2] ; Silva Sasso, Gisela Rodrigues ^[3] ; Simoes, Manuel de Jesus ^[3] ; Pinheiro Baracat, Maria Candida ^[2] ; Baracat, Edmund Chada ^[2] ; Soares-, Jr., Jose Maria ^[2]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Escola Paulista Med, Dept Gynecol, Sao Paulo - Brazil

^[2] Univ 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

^[3] Univ Fed Sao Paulo, Escola Paulista Med, Dept Morphol & Genet, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF OVARIAN RESEARCH; v. 11, MAR 1 2018.
• Citações Web of Science: 5

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; 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. (AU)

• Processo FAPESP: 09/54019-9 - Efeito da metformina na resistencia insulinica e na melatonina em adolescentes com sindrome dos ovarios policisticos
• Beneficiário: José Maria Soares Junior
• Modalidade de apoio: Auxílio à Pesquisa - Regular