Tianjin Key Laboratory of Human Development and Reproductive Regulation, Department of Gynecology, Tianjin Central Gynecology and Obstetrics Hospital Affiliated to Nankai University, Tianjin, China.
Department of Obstetrics and Gynecology, Second Xiangya Hospital of Central South University, Hunan, China.
J Cell Mol Med. 2021 Jan;25(2):1128-1139. doi: 10.1111/jcmm.16179. Epub 2020 Dec 7.
Interleukin 18 (IL-18) is a pleiotropic pro-inflammatory cytokine and is associated with arrested follicle development and anovulation which are the typical pathological changes of PCOS. Theca cells (TCs) have a key role in follicular growth and atresia. But whether IL-18 can directly affect ovarian TCs function is unknown. Therefore, the objective of this study was to determine the effect of IL-18 on proliferation and steroidogenesis of bovine TCs and to explore the biological effect of IL-18 on folliculogenesis. This work revealed that at 300-1000 pg/mL, IL-18 led to a time- and dose-dependently increase in cell proliferation (P < .05). IL-18 increased 17-hydroxyprogesterone (17OHP4) and androstenedione (A2) secretion with up-regulation of key steroidogenesis-related genes CYP11A1 and CYP17A1 (P < .05). Furthermore, our data demonstrated that the IL-18R protein is predominantly expressed in small-follicle (3-6 mm) TCs than large follicles (8-22 mm) by immunohistochemistry. We also found that the stimulation effects of IL-18 on TCs can be reversed with the addition of IL-18BP as early as at 4 hours of culture and reached the peak at 16 hours. We conclude that IL-18 appears to target TCs in bovine, and suggest an important role for this cytokine in ovarian function. Present findings further validate potential effects of IL-18 in the conditions associated with follicular dysplasia and excessive growth of ovarian TCs (such as PCOS). But additional research is needed to further understand the mechanism of action of IL-18 in theca cells as well as its precise role in folliculogenesis.
白细胞介素 18 (IL-18) 是一种多功能促炎细胞因子，与卵泡发育停滞和排卵障碍有关，这是 PCOS 的典型病理变化。卵泡膜细胞 (TCs) 在卵泡生长和闭锁中起关键作用。但是，IL-18 是否可以直接影响卵巢 TCs 的功能尚不清楚。因此，本研究旨在确定 IL-18 对牛 TCs 增殖和类固醇生成的影响，并探讨 IL-18 对卵泡发生的生物学影响。本研究表明，在 300-1000 pg/mL 时，IL-18 导致细胞增殖呈时间和剂量依赖性增加（P <.05）。IL-18 增加了 17-羟孕酮 (17OHP4) 和雄烯二酮 (A2) 的分泌，并上调了关键的类固醇生成相关基因 CYP11A1 和 CYP17A1（P <.05）。此外，我们的数据通过免疫组织化学显示，IL-18R 蛋白主要在小卵泡 (3-6mm) TCs 中表达，而在大卵泡 (8-22mm) 中表达较少。我们还发现，早在培养 4 小时后，添加 IL-18BP 即可逆转 IL-18 对 TCs 的刺激作用，16 小时达到高峰。我们得出结论，IL-18 似乎针对牛的 TCs，表明这种细胞因子在卵巢功能中起重要作用。目前的研究结果进一步验证了 IL-18 在与卵泡发育不良和卵巢 TCs 过度生长相关的条件下的潜在作用（如 PCOS）。但是，需要进一步的研究来进一步了解 IL-18 在卵泡膜细胞中的作用机制及其在卵泡发生中的精确作用。
