Chemokine Ligand 20: A Signal for Leukocyte Recruitment During Human Ovulation?
Chemokine Ligand 20: A Signal for Leukocyte Recruitment During Human Ovulation?
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DOI：
10.1210/en.2014-1874
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发表时间：
2015-09-01
期刊：
影响因子：
4.8
通讯作者：
Curry, Thomas E., Jr.
中科院分区：
文献类型：
--
作者：
Al-Alem, Linah;Puttabyatappa, Muraly;Curry, Thomas E., Jr.
排卵是女性生育能力的基石之一。排卵过程中断会导致不孕，影响大约 10% 的夫妇。使用一种独特的模型，在女性的排卵期期间收集优势卵泡，我们在人类卵巢中鉴定出了白细胞趋化剂，趋化因子配体 20 (CCL20)。在给予 hCG 后的排卵早期（12-18 小时）和排卵晚期（18-34 小时）期间收集的颗粒细胞（>10000 倍）和卵泡膜细胞（>4000 倍）中，体内人绒毛膜促性腺激素 (hCG) 刺激后，CCL20 mRNA 被大量诱导。由于 LH 激增引发以白细胞涌入为特征的炎症反应，并且已知 CCL20 会在其他系统中募集白细胞，因此在排卵前立即测定了含有 CCL20 受体 CCR6 的卵巢白细胞 (CD45+) 的组成。 CD45+/CCR6+ 细胞主要是自然杀伤细胞 (41%)，此外还有 B 细胞 (12%)、T 细胞 (11%)、中性粒细胞 (10%) 和单核细胞 (9%)。重要的是，外源性 CCL20 在 90 分钟内刺激卵巢白细胞迁移 59%。由于获得人类卵泡的困难，利用颗粒叶黄素细胞开发了体外模型来探索CCL20的调控。 hCG后6小时内CCL20表达增加40倍，部分受到上皮生长因子途径的调节，并且与孕激素的产生呈正相关。这些结果表明，hCG 显着增加人卵巢中 CCL20 的表达，卵巢白细胞含有 CCL20 受体，并且 CCL20 刺激白细胞迁移。我们的研究结果提出了这样的前景：CCL20 可能有助于最终的排卵事件并有助于女性的生育能力。
Ovulation is one of the cornerstones of female fertility. Disruption of the ovulatory process results in infertility, which affects approximately 10% of couples. Using a unique model in which the dominant follicle is collected across the periovulatory period in women, we have identified a leukocyte chemoattractant, chemokine ligand 20 (CCL20), in the human ovary. CCL20 mRNA is massively induced after an in vivo human chorionic gonadotropin (hCG) stimulus in granulosa (>10 000-fold) and theca (>4000-fold) cells collected during the early ovulatory (12-18 h) and late ovulatory (18-34 h) periods after hCG administration. Because the LH surge sets in motion an inflammatory reaction characterized by an influx of leukocytes and CCL20 is known to recruit leukocytes in other systems, the composition of ovarian leukocytes (CD45+) containing the CCL20 receptor CCR6 was determined immediately prior to ovulation. CD45+/CCR6+ cells were primarily natural killer cells (41%) along with B cells (12%), T cells (11%), neutrophils (10%), and monocytes (9%). Importantly, exogenous CCL20 stimulated ovarian leukocyte migration 59% within 90 minutes. Due to the difficulties in obtaining human follicles, an in vitro model was developed using granulosa-lutein cells to explore CCL20 regulation. CCL20 expression increased 40-fold within 6 hours after hCG, was regulated partially by the epithelial growth factor pathway, and was positively correlated with progesterone production. These results demonstrate that hCG dramatically increases CCL20 expression in the human ovary, that ovarian leukocytes contain the CCL20 receptor, and that CCL20 stimulates leukocyte migration. Our findings raise the prospect that CCL20 may aid in the final ovulatory events and contribute to fertility in women.