CCL20-CCR6 axis directs sperm–oocyte interaction and its dysregulation correlates/associates with male infertility‡
| Autor: | S-J Chen, U P Wehry, Holger Schrumpf, Jens Hirchenhain, H-C Schuppe, Bernhard Homey, C-F Yu, Gerhard Haidl, Anke van Lierop, J. S. Krüssel, Yonggang Duan, Zhi-Ming Cai, Anja Müller, Natalija Novak, Erich Bünemann, J.-P. Allam, Péter Oláh, Bettina Alexandra Buhren, Peter Arne Gerber |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Receptors CCR6 0301 basic medicine endocrine system Chemokine Acrosome reaction chemical and pharmacologic phenomena Biology 03 medical and health sciences Chemokine receptor 0302 clinical medicine Capacitation Testis medicine Humans Infertility Male Sperm-Ovum Interactions Chemokine CCL20 Granulosa Cells 030219 obstetrics & reproductive medicine urogenital system Chemotaxis hemic and immune systems Cell Biology General Medicine Microarray Analysis Oocyte Immunohistochemistry Spermatozoa Sperm Follicular Fluid Cell biology CCL20 030104 developmental biology medicine.anatomical_structure Follicular Phase Gene Expression Regulation Reproductive Medicine Oocytes biology.protein Female Chemokines |
| Zdroj: | Biology of Reproduction. 103:630-642 |
| ISSN: | 1529-7268 0006-3363 |
| DOI: | 10.1093/biolre/ioaa072 |
| Popis: | 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 toward 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.Graphical AbstractSummary SentenceThe chemokine CCL20 is produced by human oocytes as well as surrounding cumulus granulosa cells and induces chemotaxis of CCR6+ sperm. Infertile male donors demonstrate increased levels of CCL20 in testis and seminal fluid, which may negatively influence sperm–oocyte interaction. |
| Databáze: | OpenAIRE |
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