A restrição calórica mantém a reserva ovariana e melhora parâmetros metabólicos independentemente da idade em camundongos

Abstract

Female reproductive aging progresses until menopause, marked by a progressive depletion of the ovarian reserve and a reduction in primordial follicles, leading to a decline in fertility and greater reproductive challenges in older women. Critical processes, such as the activation of primordial follicles, are influenced by PI3K/AKT and mTORC1 pathways, which play a central role in this loss of reserve. Oocyte quality also deteriorates over time due to DNA damage and environmental influences. Menopause, besides ending the reproductive period, brings significant hormonal changes that affect various areas beyond reproduction, such as metabolic health, and predisposition to various diseases. However, a delayed menopause can indicate greater longevity and quality of life, underlining the relevance of the ovarian reserve for the overall life expectancy. Strategies like caloric restriction (CR), which reduces calorie intake without causing malnutrition, emerge as promising methods to preserve the ovarian reserve and extend the reproductive phase, supported by benefits such as inflammation reduction, strengthening of antioxidant defenses, and improvements in metabolic health in animal models. We investigated the effects of CR on the ovarian reserve and metabolic parameters in young (3 months) and middle-aged (7 months) female mice. The animals in the CR group underwent a 30% caloric restriction, based on the food intake of the control group, over a period of 4 months (equivalent to 16 weeks). A 3-month control group was also used to observe aspects of metabolic and reproductive aging. After the intervention, an insulin tolerance test (ITT) was performed, and euthanasia was conducted for organ collection (adipose tissue and ovary). As a result of the study, CR led to a similar weight loss in the 3-7 and 7-11 month groups. CR also reduced weight gain during the intervention period and decreased abdominal adipose tissue. The glucose decay rate was significantly higher in both CR groups, regardless of age. The analysis of the ovarian reserve revealed a higher number of primordial follicles in the 3-7 and 7-11 month CR groups compared to controls. However, CR had no effect on transition, primary, and secondary follicles. Age-related reductions were observed in primordial, primary, and secondary follicles. The number of tertiary follicles showed a significant interaction, with the 3-7 CR group displaying fewer follicles compared to its control, unlike the 7-11 month groups. The total number of follicles did not differ between groups but decreased with age. Thus, our findings highlight the efficacy of CR in promoting reproductive longevity through the preservation of the ovarian reserve and improvement of metabolic aspects regardless of the age os start.