Mouse ovarian disturbances caused by a high fat diet: the effect of metformin on ovarian function restoration

VELAZQUEZ C; CARNOVALE N; BILOTAS M; MERESMAN G; HERRERO Y; MARINONI R; PARBORELL F; ABRAMOVICH D

Mar del Plata

Congreso; Reunión Anual Conjunta de las Sociedades SAIC, SAI y SAFIS.; 2022

SAIC

Introduction: Female reproductive performance is affected by metabolic deregulations. Nowadays, many women are overweight, so understanding the impact of a high fat diet (HFD) is imperative.Folliculogenesis takes place in the ovary and depends on a correct blood supply, therefore, alterations of angiogenesis may have consequences. Metformine (MET) is a hypoglycemic drug administrated in diabetic type 2 patients that was shown to improve ovulation and pregnancy rates in women. The mechanisms underlying these effects are still unclear.Objective: To analyze the effects of HFD and MET on metabolism and reproductive function in female mice.Methodology: 21d.o. female C57BL/6 mice were fed with a HFD or a control diet for 16 weeks. One HFD and one control group received MET the last four weeks. Mice were weighted once a week. Serum, gonadal and visceral fat were obtained. Estrus cycle and metabolic parameters were evaluated. Ovaries were isolated to perform WB and histology. One-way-ANOVA was used for statistical analysis.Results: HFD-mice had higher body weight, glycemia, GTT, HOMA-IR, t-cholesterol, P4 and adipose tissue. MET improved GTT, HOMA-IR and decreased adipose tissue and P4. The estrus cycle was shorter in HFD and the number of cycles/14d was increased. However, anovulatory stages were longer in HFD. MET had no effect on estrous cycle. The follicular dynamic was altered in HFD and MET improved it, raising the percentage of corpora lutea and primary follicles. Atretic follicles were higher on HFD with no effect of MET. Ovarian VEGF and DNA damage were elevated while periendothelial cell area was decreased in HFD. MET reversed these alterations and improved the 3β-HSD increase and the periendothelial cell area decrease found in HFD. Conclusion: HFD affects metabolism, hormonal profile, estrous cycle, angiogenesis and folliculogenesis. Changes in ovarian VEGF may be one of the possible causes of the observed disturbances. MET improves some of these alterations.KEY WORDS: High fat diet, ovary, angiogenesis, metabolism