Division of Farm Animal Health, Department Population Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands; Amsterdam Institute for Life and Environment, Section Environment and Health, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
Amsterdam Institute for Life and Environment, Section Environment and Health, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
Reprod Toxicol. 2024 Sep;128:108637. doi: 10.1016/j.reprotox.2024.108637. Epub 2024 Jun 12.
Ketoconazole (KTZ) is widely used as a fungicide, but it is also known to target steroid hormone formation which may affect female reproductive health. Our study aims to investigate the effects of KTZ on in vitro matured bovine cumulus-oocyte complexes (COCs), as a model for female reproductive toxicity. Cumulus cells of in vitro maturing COCs produce progesterone and pregnenolone, but exposure to 10 M KTZ effectively blocked the synthesis of these hormones. Exposure to lower concentrations of KTZ (i.e. 10 M and 10 M) had no such effect on steroidogenesis compared to the 0.1 % v/v DMSO vehicle control. Classical parameters of in vitro COC maturation, such as oocyte nuclear maturation to the metaphase II stage and expansion of the cumulus investment, were not affected by any KTZ concentration tested. Apoptosis and necrosis levels were also not altered in cumulus cells or oocytes exposed to KTZ. Moreover, oocytes exposed to KTZ during maturation showed normal cleavage and early embryo development up to day 8 post fertilization; albeit a statistically significant decrease was observed in day 8 blastocysts produced from oocytes exposed to the lowest concentration of 10 M KTZ. When unexposed mature oocytes were fertilized, followed by embryo culture for 8 days under KTZ exposure, no adverse effects in embryo cleavage and blastocyst formation were observed. In conclusion, KTZ has no major impact on in vitro bovine oocyte maturation and blastocyst formation in our study, even at concentrations blocking steroidogenesis.
酮康唑（KTZ）被广泛用作杀菌剂，但它也被认为是靶向甾体激素形成的物质，这可能会影响女性生殖健康。我们的研究旨在研究 KTZ 对体外成熟牛卵丘-卵母细胞复合物（COC）的影响，作为女性生殖毒性的模型。体外成熟 COC 的卵丘细胞产生孕酮和孕烯醇酮，但暴露于 10 M KTZ 可有效阻断这些激素的合成。与 0.1%v/v DMSO 载体对照相比，暴露于较低浓度的 KTZ（即 10 M 和 10 M）对甾体生成没有这种作用。体外 COC 成熟的经典参数，如卵母细胞核成熟到中期 II 阶段和卵丘细胞的扩展，不受任何测试浓度的 KTZ 影响。凋亡和坏死水平在暴露于 KTZ 的卵丘细胞或卵母细胞中也没有改变。此外，在成熟过程中暴露于 KTZ 的卵母细胞显示出正常的分裂和早期胚胎发育，直到受精后第 8 天；尽管从暴露于最低浓度 10 M KTZ 的卵母细胞中产生的第 8 天囊胚的数量明显减少。当未暴露的成熟卵母细胞受精后，在 KTZ 暴露下进行胚胎培养 8 天，在胚胎分裂和囊胚形成中未观察到不良反应。总之，在我们的研究中，即使在阻断甾体生成的浓度下，KTZ 对体外牛卵母细胞成熟和囊胚形成也没有重大影响。
