17alfa-Estradiol e restrição calórica no envelhecimento reprodutivo de machos e fêmeas

Abstract

17α-estradiol (17α-E2) is a well-established pro-longevity intervention with benefits to male mice healthspan. However, no studies assessing 17α-E2 effects on male fertility had been reported so far, hence we aimed to evaluate the effects of 17α-E2 on fertility of mice from both sexes and also ovarian aging. 17α-E2 has been shown to decrease feed intake in a similar fashion that a mild calorie restriction (CR). However, the effects of mild CR (10%) on ovarian aging had not yet been addressed. Hence, we also assessed effects of mild calorie restriction on female ovarian aging and fertility in contrast to 17α-E2 and a standard – moderate (30%) – CR. For this purpose, we subjected C57BL/6 female mice (n=9/group) to treatment with 17α-E2 or two levels of CR over a 24-week period. In these mice we evaluated ovarian reserve, embryo production, pregnancy rate and litter size. Both 10% and 30% CR elicited positive effects on the preservation of the ovarian reserve, whereas 17α-E2 did not affect parameters associated with ovarian function. Following refeeding, both 10% and 30% increased fertility as evidenced by greater pregnancy rates. 17α-E2 however, failed to improve ovarian reserve preservation or fertility. For the male fertility assessment, two cohorts of male C57BL/6 mice were supplemented with 17α-E2 (n=10 and 30) from three to seven or eight months of age. These mice were mated with non-treated previously synchronized three-month-old females for embryo collection or counting of uterine implantation sites. Plasma hormonal levels, sperm quality, testes morphology were also evaluated. Despite males treated with 17α-E2 having lower body weight gain, no differences were found for the totality of the reproductive variables, showing that 17α-E2 does not affect the fertility of adult male mice. Collectively, our data indicate that 14.4 ppm of 17α-E2, which is established as effective to improve healthspan effects in male mice, does not affect reproductive parameters in mice of both sexes, and also fails to affect ovarian aging in female mice.