Calorie restriction increases primordial follicle reserve in mature female chemotherapy-treated rats

We assessed the effects of calorie restriction (CR)-mediated protection against chemotherapy damage on ovarian reserve. Forty-eight female Sprague-Dawley rats were randomly divided into four groups: the normal control group (NC group, fed ad libitum), the CR group (fed with 65% food intake of the NC group), the CTX group (injected with cyclophosphamide (CTX) and fed ad libitum), and the CR + CTX group (injected with CTX and fed with 65% food intake of the NC group). Ovarian reserve was examined by vaginal smears and follicle counting. SIRT1 is a deacetylase that is activated by a variety of stressors and targets transcriptional regulators including p53, NF-κB, FOXO1, 3, and 4, and the transcriptional regulator PGC-1α. The expression level of SIRT1, p53 and FOXO3a in the ovary was measured by western blot. CR did not interfere with estrous cycling but maintained estrous cycling in CTX-treated CR rats. The number of primordial follicles in the CR rats was comparable to the NC group, and CR + CTX group rats had more primordial follicles and primary follicles than the CTX group. SIRT1 expression in the ovary was higher in the CR group compared to the control group, and p53 level was lower in the CR group than that in the NC group. There is no significant difference in the expression level of FOXO3a between the CR group and the NC group. Conclusions: These results indicate that CR can increase the ovarian follicular reserve and reduce the CTX-induced ovarian damage, and CR positive effects may be due to its intervention in the transition from primordial to primary follicle, and its reduction of oxidative stress.