Senescência celular e efeito de tratamento com senolíticos no ovário de camundongos geneticamente obesos.

Abstract

Leptin-deficient (ob/ob) mice are obese and sterile. This experimental model is an important tool for studies of obesity and related comorbidities. Senescent cells are present in numerous tissues of the organism, in greater quantity during aging and obesity, contributing to the increase of tissue inflammation. Treatment with senolytic drugs dasatinib and quercetin (D+Q) has the ability to selectively reduce senescent cells in various organs, increasing longevity and reducing symptoms of aging. Despite this, there is no data on whether these cells are present in the female reproductive organs. In addition, the characterization of the ovarian reserve of this obese model is scarce. Therefore, the aim of the study was to characterize the ovarian reserve and its association with cellular senescence in obese mice. For this, 10 animals were used in experiment 1, where ob/ob mice (n=5) and wild type lean mice (WT) (n=5) were euthanized at 12 months to collect ovarian tissue. Experiment 2 consisted of (n=12) female ob/ob mice divided into control (n=6) and treatment (n=6) groups. The treatment group received senolytics (D+Q) starting at two months of age via gavage every two weeks, while the control group received a placebo in the same period. These mice were euthanized at 6 months of age and the ovaries were collected for analysis. In experiment 1, there was no difference in the size of the ovarian reserve between ob/ob and WT mice (P>0.05). However, there was more senescent cells in the ovary of obese females, as well as increased body weight and periovarian fat. In experiment 2, there was no difference in the size of the ovarian reserve and in insulin sensitivity (P>0.05) in control and D+Q treated females. However, there was a decrease in senescence in the ovary of treated obese mice. In conclusion, although we observed more senescence in obese females, it did not significantly affect the ovarian reserve. The treatment with D+Q reduced the senescent load but did not reflect in the ovarian reserve of ob/ob mice treated with D+Q.