Metformin and female reproduction: effects on physiological and pathological conditions.

CANDELA VELAZQUEZ; YAMILA HERRERO; MARIA SILVIA BIANCHI; DEBORAH COHEN; PATRICIA CUASNICU; KATHERINE PROST; ROCIO MARINONI; MAYRA BORDAQUIEVICH; MELANIE NEIRA

Valdivia

Congreso; V Meeting Latin American Chapter Developmental Origins of Health and Disease (DOHaD) Society - XXXIV Meeting Chilean Society of Reproduction and Development; 2023

Chilean Society of Reproduction and Development Joint Meeting.

Background: Metformin is a hypoglycemic drug used for type-2 diabetes that acts on the female reproductive system through unclear mechanisms. Since female fertility depends on energy balance and blood supply, a high-fat diet (HFD) may have detrimental consequences and metformin could improve them.Methods: A)14-weeks old C57BL/6 mice were divided into two groups. One group received metformin orally. The other, water only. After 4 weeks, animals were split into 3 subsets. In one subset, blood and the ovaries were collected to measure hormones and follicular dynamic. The other subset was mated with males and the time to pregnancy and offspring features were analyzed. The third subset underwent in vitro fertilization (IVF).B) 21-days old C57BL/6 mice were fed for 15 weeks with regular chow or HFD. Body weight was determined once a week. At week 11, some HFD animals received metformin orally, for 4 weeks. Then, animals from the three groups were split and analyzed as explained in A.Results: A)Metformin reduced primary follicles, pup’s weight, ovarian VEGF and progesterone levels. Estradiol levels and preantral follicles were higher. No differences were found after IVF. B)HFD mice had higher body weight, adipose tissue, ovarian VEGF, time to pregnancy and progesterone levels, with no differences in estradiol. We found a smaller number of pups per litter with no differences in pups’ weight. Metformin restored these alterations. The % of newly-formed corpora lutea was lower in HFD. Metformin increased this % to control values. After IVF, fewer oocytes were retrieved, with no effect of metformin. Conclusions: Metformin has an effect on ovarian performance in physiological and pathological conditions, being able to restore the majority of reproductive alterations caused by a HFD. Altered ovarian angiogenesis may be one of the possible mechanisms that explains HFD and metformin effects.