Análise imunoistoquímica e histológica dos efeitos da metformina no ovário em ratas androgenizadas

• Ano de defesa: 2013
• Autor(a) principal: Antonini, Moberta Rassi Mahamed [UNIFESP]
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo (UNIFESP)
• Palavras-chave em Português: polycystic ovarian syndrome; vascular endothelial growth factor; cellular proliferation; metformin; rats; síndrome do ovário policístico; fator de crescimento endotelial vascular; proliferação celular; metformina; ratos
• Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=864434; https://repositorio.unifesp.br/handle/11600/47582

Objective: To analyze immunohistochemically and morphology the ovaries of metformin-treated and neonatally androgenized female rats in permanent estrus. Materials and Methods: Forty-five newly born female albino Wistar EPM-1 rats were randomized on their third day of life to 3 groups of 15 animals each as follows: control group (CG), androgenized group (AG), and androgenized +metformin group (AGmet). The AG and AGmet animals received a single dose of 0.1 ml of testosterone propionate (1.25 mg/animal) diluted in castor oil (vehicle), and the controls, only vehicle, by subcutaneous injection in the dorsum. Nine animals died during the drug administration; 36 animals remained. After 90 days, the 6-week-long daily gavage treatment was initiated. The CG and the AG rats received distilled water, while the AGmet animals were treated with metformin (50mg/kg). Next, 12 animals from CG, 10 from AG, and 14 from AGmet were anesthetized, blood was drawn for glucose and fasting glucose measurements, and the ovaries were removed for histological and immunohistochemical analyses. The data were analyzed using the ANOVA and the Tukey tests. Results: The glucose and the HOMA-IR values were highest in the AG rats (p<0.01). Histomorphometric analysis of the ovaries showed a reduction in the area of degenerating follicles and in the number of interstitial cells and the emergence of corpora lutea in AGmet as against AG (p<0.01). Proliferation decreased in the theca interna and in the interstitial cells as evidenced by Ki-67, and VEGF-A expression diminished in the theca interna, the granulosa, and the interstitial cells in AGmet. Conclusion: Metformin led to improvement in glucose and in the HOMA-IR index, to partial reversion of histomorphometric characteristics, and to reduction in ovarian cell proliferation in previously androgenized rat ovaries as shown by Ki-67 and VEGF-A.