The interaction of sperm with the oocyte is pivotal during the process of mammalian fertilization. The limited numbers of sperm that reach the fallopian tube as well as anatomic restrictions indicate that human sperm-oocyte encounter is not a matter of chance but a directed process. Chemotaxis is the proposed mechanism for re-orientating sperm towards the source of a chemoattractant, and hence to the oocyte. Chemokines represent a superfamily of small (8-11 kDa), cytokine-like proteins that have been shown to mediate chemotaxis and tissue-specific homing of leukocytes through binding to specific chemokine receptors such as CCRs. Here we show that CCR6 is abundantly expressed on human sperms and in human testes. Furthermore, radioligand-binding experiments showed that CCL20 bound human sperm in a specific manner. Conversely, granulosa cells of the oocyte-surrounding cumulus complex as well as human oocytes represent an abundant source of the CCR6-specific ligand CCL20. In human ovaries, CCL20 shows a cycle-dependent expression pattern with peak expression in the preovulatory phase and CCL20 protein induces chemotactic responses of human sperm. Neutralization of CCL20 in ovarian follicular fluid significantly impairs sperm migratory responses. Conversely, analyses in infertile men with inflammatory conditions of the reproductive organs demonstrate a significant increase of CCL20/CCR6 expression in testis and ejaculate. Taken together, findings of the present study suggest that CCR6-CCL20 interaction may represent an important factor in directing sperm-oocyte interaction.

中文翻译：

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CCL20-CCR6 轴指导精子-卵母细胞相互作用，其失调与男性不育症相关/关联‡。

精子与卵母细胞的相互作用在哺乳动物受精过程中至关重要。到达输卵管的精子数量有限以及解剖结构限制表明，人类精子与卵母细胞的相遇不是偶然的，而是一个有针对性的过程。趋化性是建议的机制，用于将精子重新定向到化学引诱物的来源，从而重新定向到卵母细胞。趋化因子代表了一个小 (8-11 kDa) 细胞因子样蛋白的超家族，这些蛋白已被证明通过与特定的趋化因子受体（如 CCR）结合来介导白细胞的趋化性和组织特异性归巢。在这里，我们表明 CCR6 在人类精子和人类睾丸中大量表达。此外，放射性配体结合实验表明，CCL20 以特定方式结合人类精子。反过来，卵母细胞周围卵丘复合体的颗粒细胞以及人类卵母细胞代表了 CCR6 特异性配体 CCL20 的丰富来源。在人类卵巢中，CCL20 显示出周期依赖性表达模式，在排卵前阶段达到峰值，CCL20 蛋白诱导人类精子的趋化反应。中和卵巢卵泡液中的 CCL20 会显着损害精子迁移反应。相反，对患有生殖器官炎症的不育男性的分析表明，睾丸和射精中 CCL20/CCR6 的表达显着增加。总之，本研究的结果表明，CCR6-CCL20 相互作用可能是指导精子-卵母细胞相互作用的一个重要因素。