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

VELAZQUEZ C; CARNOVALE N; BILOTAS M; MARINONI R; HERRERO Y; POMPONIO V; PROST K; MERESMAN G; PARBORELL MF; ABRAMOVICH D

Congreso; LXVII reunión anual de la sociedad argentina de investigación clínica (SAIC); 2022

Introduction: Female reproductive performance is affected by metabolicderegulations. Nowadays, many women are overweight, sounderstanding the impact of a high fat diet (HFD) is imperative.Folliculogenesis takes place in the ovary and depends on a correctblood supply, therefore, alterations of angiogenesis may have consequences.Metformine (MET) is a hypoglycemic drug administratedin diabetic type 2 patients that was shown to improve ovulationand pregnancy rates in women. The mechanisms underlying theseeffects are still unclear. Objective: To analyze the effects of HFDand MET on metabolism and reproductive function in female mice.Methodology: 21d.o. female C57BL/6 mice were fed with a HFD or acontrol diet for 16 weeks. One HFD and one control group receivedMET the last four weeks. Mice were weighted once a week. Serum,gonadal and visceral fat were obtained. Estrus cycle and metabolicparameters were evaluated. Ovaries were isolated to perform WBand 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 cyclewas shorter in HFD and the number of cycles/14d was increased.However, anovulatory stages were longer in HFD. MET had no effecton estrous cycle. The follicular dynamic was altered in HFD andMET improved it, raising the percentage of corpora lutea and primaryfollicles. Atretic follicles were higher on HFD with no effect of MET.Ovarian VEGF and DNA damage were elevated while periendothelialcell area was decreased in HFD. MET reversed these alterationsand improved the 3β-HSD increase and the periendothelial cellarea 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 theobserved disturbances. MET improves some of these alterations.