Cycloastragenol Attenuates Cisplatin‐Induced Ovarian Toxicity in Rats: Associations With TERT Expression, Apoptotic Balance, and FOXO3a–mTOR‐Related Signaling

Cisplatin (CIS)‐induced ovarian toxicity is characterized by follicular depletion, apoptosis, and disruption of intracellular survival signaling. This study investigated whether cycloastragenol (CAG), a telomerase‐associated bioactive compound, attenuates CIS‐induced ovarian injury in rats. Forty female Sprague–Dawley rats were assigned to two vehicle‐control groups and CAG, CIS, or CIS + CAG groups for 15 days. Vehicle controls were pooled after confirming no significant differences. Ovarian morphology and follicle counts were evaluated histologically. Immunohistochemical analyses included PCNA, caspase‐3, total FOXO3a, phospho‐FOXO3a (Ser253), total mTOR, BAX, BCL‐2, and TERT. Serum anti‐Müllerian hormone and telomerase‐related measurements were assessed by ELISA, and relative telomere length was determined by quantitative real‐time PCR. CIS reduced primordial follicle numbers, increased follicular atresia, enhanced BAX expression, reduced BCL‐2 and TERT immunoreactivity, and increased the BAX/BCL‐2 ratio. CAG co‐treatment significantly attenuated the changes in BAX, BCL‐2, the BAX/BCL‐2 ratio, and TERT. Nuclear phospho‐FOXO3a was significantly lower in the CIS + CAG group than in the CIS group, whereas cytoplasmic phospho‐FOXO3a did not differ significantly. Total mTOR and caspase‐3 were numerically reduced by CAG co‐treatment but did not remain significant after multiple‐comparison correction. PCNA, total FOXO3a, and serum AMH showed partial or nonsignificant recovery. Relative telomere length did not differ among groups. CAG partially attenuated CIS‐induced ovarian injury and apoptotic imbalance and was associated with restoration of ovarian TERT immunoreactivity and modulation of phospho‐FOXO3a localization. However, these findings do not establish a causal telomerase–FOXO3a–mTOR mechanism.