Targeting a novel tamoxifen-using pathway to preserve ovarian reserve in rats with experimental chemotherapy-induced ovarian failure

Due to the increased incidence of cancer in young women, chemotherapy-induced gonad toxicity, such as that caused by cyclophosphamide (CP), is now the main cause of premature ovarian insufficiency (POI). The current work investigates how CP damages the rat ovary and whether tamoxifen (TAM) medication and pretreatment can reduce CP by restoring antioxidant and mitochondrial balance. Forty adult female albino rats were randomly allocated into four groups. The control group and CP-induced POI group were used. TAM pretreatment for four weeks prior to CP injection in the third group. A single dosage of TAM was administered concurrently with CP in the fourth group. In the group receiving CP, the following observations were observed: a reduction in the ovarian index; a decline in the numbers of primordial and primary follicles; an increase in atretic follicles; a decrease in mRNA expression of insulin-like growth factor 1 (IGF-1) and its receptor (IGF-1R); a significant reduction in anti-Müllerian hormone (AMH); an increase in serum levels of dynamin-related protein (DRP-1); a decrease in serum levels of interleukin 10 (IL-10), nitric oxide (NO), and mitofusin 1 (MFN-1); a damaged ovarian tissues that evaluated histopathologically; an decrease in the number of primordial and primary follicles; an increase in the number of atretic follicles; zona pellucida’s integrity disruption; an decrease in ovarian weights; and an increase in collagen fiber area percentages; a decrease in heme oxygenase-1 (HO-1) immunoreactivity; and an increase in the expression of immunopositive cells for cluster of differentiation 86 (CD86) compared to controls. In contrast, both treatment and pretreatment with TAM improved these effects. With concern to pretreatment with TAM that showed a superior improvement in increasing the number of primordial and primary follicles, improving cortical follicles, enhancing zona pellucida’s integrity and increasing in HO-1immunoreactivity combined with limited regions of collagen fibers. One possible explanation for the protective effects of TAM on ovarian tissue is that it increases IGF-1 mRNA expression, improves mitochondrial dynamic balance, and activates the IL-10/HO-1 pathway, all of which work together to decrease oxidative stress and increase ovarian tissue survival. Based on our research, it appears that a potentially effective regimen for POI caused by CP is pretreatment with TAM. This could lead to a higher percentage of POI disease remission.