Faculty of Veterinary Medicine, Laboratory of Manipulation of Oocyte and Preantral Follicles (LAMOFOPA), State University of Ceara, Avenue Silas Munguba 1700, 60740-000, Fortaleza, CE, Brazil.
Laboratory of Biology of Reproduction, Federal University of Uberlândia, Minas Gerais, Brazil.
Reprod Toxicol. 2019 Mar;84:18-25. doi: 10.1016/j.reprotox.2018.12.007. Epub 2018 Dec 21.
The Withanolide D is a chemotherapeutic potential against the human tumor cell. However, there is no report on the effect of this compound on ovarian function, especially on preantral folliculogenesis. The aim of this study was to evaluate the toxicity of a new candidate to anticancer drug, Withanolide D (WD) on morphologic integrity, development (activation and granulosa cell proliferation) and gene expression of ABCB1 protein of caprine preantral follicles. Ovarian fragments were cultured in vitro for 2 or 6 days in α-MEM or α-MEM added with paclitaxel (PTX -0.1 μg/mL; negative control) and different concentrations of WD (WD1.5, WD3.0 or WD6.0). The higher dose of WD showed a toxic effect similar to PTX and higher (P < 0.05) than other treatments after 2 and 6 days. In addition, WD6.0 reduced the cell proliferating compared to PTX or mild dose. The expression of ABCB1 remained unchanged in the presence of the chemotherapeutic agents (PTX and WD) throughout the culture period. In conclusion, WD exerted a toxic effect observed by decreasing follicular survival and cell proliferation, on the preantral caprine follicles similar to PTX, whose negative effect on folliculogenesis is already widely known.
Withanolide D 是一种具有化疗潜力的人肿瘤细胞。然而，关于这种化合物对卵巢功能的影响，特别是对原始卵泡发生的影响，尚无报道。本研究旨在评估一种新的候选抗癌药物，即 Withanolide D（WD）对山羊原始卵泡形态完整性、发育（激活和颗粒细胞增殖）和 ABCB1 蛋白基因表达的毒性。卵巢片段在α-MEM 或添加紫杉醇（PTX-0.1μg/mL；阴性对照）和不同浓度 WD（WD1.5、WD3.0 或 WD6.0）的α-MEM 中体外培养 2 或 6 天。较高剂量的 WD 在 2 天和 6 天后表现出类似于 PTX 的毒性作用，且高于（P<0.05）其他处理组。此外，与 PTX 或低剂量相比，WD6.0 降低了细胞增殖。在整个培养期间，存在化疗药物（PTX 和 WD）时，ABCB1 的表达保持不变。总之，WD 对山羊原始卵泡的存活和细胞增殖产生了毒性作用，这与 PTX 相似，PTX 对卵泡发生的负面影响已广为人知。
