Karaoğlan Özdem, Kuyucu Yurdun, Şaker Dilek, Dağlıoğlu Gülçin, Tap Özgül
Department of Histology and Embryology, Faculty of Medicine, Cukurova University, Adana 01170, Turkey.
Int J Mol Sci. 2025 Aug 12;26(16):7772. doi: 10.3390/ijms26167772.
In this study, we evaluated the protective effects of combined melatonin and vitamin D3 treatment on ovarian reserve and tissue architecture in a cyclophosphamide-induced premature ovarian failure (POF) rat model. Forty-nine adult female rats were randomly assigned to seven groups, including intact control (group 1), single-agent control (groups 2 and 3), POF (group 4), and POF + treatment (groups 5, 6, and 7) groups. Cyclophosphamide exposure led to elevated FSH and LH levels, reduced estradiol and progesterone levels, extensive follicular atresia, stromal fibrosis, and the marked degeneration of the ovarian ultrastructure. Additionally, the expression levels of PTEN, FOXO3a, and AMH were significantly downregulated, while caspase-3 and TNF-α immunoreactivities were increased. Notably, co-treatment with melatonin and vitamin D3 preserved primordial and growing follicle populations, restored hormonal balance, reduced stromal fibrosis, and attenuated apoptosis and inflammation markers. These findings highlight the potential of combined melatonin and vitamin D3 therapy as a fertility-preserving strategy that functions by mitigating chemotherapy-induced ovarian injury through multi-pathway modulation.
在本研究中，我们评估了褪黑素和维生素D3联合治疗对环磷酰胺诱导的大鼠卵巢早衰（POF）模型中卵巢储备和组织结构的保护作用。49只成年雌性大鼠被随机分为七组，包括完整对照组（第1组）、单药对照组（第2组和第3组）、POF组（第4组）以及POF + 治疗组（第5、6和7组）。环磷酰胺暴露导致促卵泡生成素（FSH）和促黄体生成素（LH）水平升高，雌二醇和孕酮水平降低，广泛的卵泡闭锁、间质纤维化以及卵巢超微结构的明显退化。此外，第10号染色体缺失的磷酸酶和张力蛋白同源物（PTEN）、叉头框蛋白O3a（FOXO3a）和抗缪勒管激素（AMH）的表达水平显著下调，而半胱天冬酶 - 3（caspase - 3）和肿瘤坏死因子 - α（TNF - α）的免疫反应性增加。值得注意的是，褪黑素和维生素D3联合治疗可保留原始卵泡和生长卵泡数量，恢复激素平衡，减少间质纤维化，并减轻凋亡和炎症标志物。这些发现凸显了褪黑素和维生素D3联合治疗作为一种生育保护策略的潜力，该策略通过多途径调节减轻化疗诱导的卵巢损伤来发挥作用。
