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Extraction, Labeling, and Purification of Lineage-Specific Cells from Human Antral Follicles
Published on: November 30, 2022
Metformin improves ovarian follicle dynamics by reducing theca cell proliferation and CYP-17 expression in an
Roberta Rassi Mahamed1,2, Carla Cristina Maganhin3, Gisela Rodrigues Silva Sasso4
1Department of Gynecology, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.
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.
Insights
Metformin treatment in androgenized rats reduced glucose and insulin levels, slowed ovarian cell proliferation, and decreased CYP-17 expression. This study highlights metformin's potential to mitigate effects of hyperandrogenism on ovarian function.
Area of Science:
- Reproductive Endocrinology
- Pharmacology
- Cell Biology
Background:
- Metformin's impact on insulin receptor signaling may affect ovarian follicular development and steroidogenesis.
- Hyperandrogenism can alter ovarian histomorphology and gene expression, including CYP-17.
- This study investigates metformin's effects in a rat model of induced hyperandrogenism.
Purpose of the Study:
- To evaluate the effect of metformin on CYP-17 expression in neonatally androgenized female rats.
- To analyze metformin's impact on follicular dynamics and cell proliferation in the ovaries.
- To assess changes in glucose and insulin levels following metformin administration.
Main Methods:
- Neonatal female rats were assigned to control, androgenized, or androgenized + metformin groups.
- Androgenization was induced using testosterone propionate; metformin was administered orally for six weeks.
- Ovarian tissues were analyzed for Ki67, VEGFA, and CYP17 expression via immunohistochemistry, alongside biochemical measurements of glucose and insulin.
Main Results:
- Metformin treatment significantly reduced body weight, glucose, and insulin levels in androgenized rats.
- The drug decreased proliferation of theca interna and interstitial cells, indicated by lower Ki-67 and VEGF-A expression.
- Metformin diminished CYP-17 expression, reduced follicle degeneration, and improved ovarian angiogenesis.
Conclusions:
- Metformin ameliorates carbohydrate metabolism disturbances in this androgenized rat model.
- The drug effectively reduces ovarian cell proliferation and CYP-17 expression.
- These findings suggest metformin's therapeutic potential for managing hyperandrogenic conditions affecting the ovaries.
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