Human fertilization in vivo and in vitro requires the CatSper channel to initiate sperm hyperactivation
The infertility of many couples rests on an enigmatic dysfunction of the man's sperm. To gain insight into the underlying pathomechanisms, we assessed the function of the sperm-specific multisubunit CatSper-channel complex in the sperm of almost 2,300 men undergoing a fertility workup, using a...
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| Published in | The Journal of clinical investigation Vol. 134; no. 1; pp. 1 - 16 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
American Society for Clinical Investigation
01.01.2024
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| Subjects | |
| Online Access | Get full text |
| ISSN | 1558-8238 0021-9738 1558-8238 |
| DOI | 10.1172/JCI173564 |
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| Abstract | The infertility of many couples rests on an enigmatic dysfunction of the man's sperm. To gain insight into the underlying pathomechanisms, we assessed the function of the sperm-specific multisubunit CatSper-channel complex in the sperm of almost 2,300 men undergoing a fertility workup, using a simple motility-based test. We identified a group of men with normal semen parameters but defective CatSper function. These men or couples failed to conceive naturally and upon medically assisted reproduction via intrauterine insemination and in vitro fertilization. Intracytoplasmic sperm injection (ICSI) was, ultimately, required to conceive a child. We revealed that the defective CatSper function was caused by variations in CATSPER genes. Moreover, we unveiled that CatSper-deficient human sperm were unable to undergo hyperactive motility and, therefore, failed to penetrate the egg coat. Thus, our study provides the experimental evidence that sperm hyperactivation is required for human fertilization, explaining the infertility of CatSper-deficient men and the need of ICSI for medically assisted reproduction. Finally, our study also revealed that defective CatSper function and ensuing failure to hyperactivate represents the most common cause of unexplained male infertility known thus far and that this sperm channelopathy can readily be diagnosed, enabling future evidence-based treatment of affected couples. |
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| AbstractList | The infertility of many couples rests on an enigmatic dysfunction of the man's sperm. To gain insight into the underlying pathomechanisms, we assessed the function of the sperm-specific multisubunit CatSper-channel complex in the sperm of almost 2,300 men undergoing a fertility workup, using a simple motility-based test. We identified a group of men with normal semen parameters but defective CatSper function. These men or couples failed to conceive naturally and upon medically assisted reproduction via intrauterine insemination and in vitro fertilization. Intracytoplasmic sperm injection (ICSI) was, ultimately, required to conceive a child. We revealed that the defective CatSper function was caused by variations in CATSPER genes. Moreover, we unveiled that CatSper-deficient human sperm were unable to undergo hyperactive motility and, therefore, failed to penetrate the egg coat. Thus, our study provides the experimental evidence that sperm hyperactivation is required for human fertilization, explaining the infertility of CatSper-deficient men and the need of ICSI for medically assisted reproduction. Finally, our study also revealed that defective CatSper function and ensuing failure to hyperactivate represents the most common cause of unexplained male infertility known thus far and that this sperm channelopathy can readily be diagnosed, enabling future evidence-based treatment of affected couples. The infertility of many couples rests on an enigmatic dysfunction of the man's sperm. To gain insight into the underlying pathomechanisms, we assessed the function of the sperm-specific multisubunit CatSper-channel complex in the sperm of almost 2,300 men undergoing a fertility workup, using a simple motility-based test. We identified a group of men with normal semen parameters but defective CatSper function. These men or couples failed to conceive naturally and upon medically assisted reproduction via intrauterine insemination and in vitro fertilization. Intracytoplasmic sperm injection (ICSI) was, ultimately, required to conceive a child. We revealed that the defective CatSper function was caused by variations in CATSPER genes. Moreover, we unveiled that CatSper-deficient human sperm were unable to undergo hyperactive motility and, therefore, failed to penetrate the egg coat. Thus, our study provides the experimental evidence that sperm hyperactivation is required for human fertilization, explaining the infertility of CatSper-deficient men and the need of ICSI for medically assisted reproduction. Finally, our study also revealed that defective CatSper function and ensuing failure to hyperactivate represents the most common cause of unexplained male infertility known thus far and that this sperm channelopathy can readily be diagnosed, enabling future evidence-based treatment of affected couples.The infertility of many couples rests on an enigmatic dysfunction of the man's sperm. To gain insight into the underlying pathomechanisms, we assessed the function of the sperm-specific multisubunit CatSper-channel complex in the sperm of almost 2,300 men undergoing a fertility workup, using a simple motility-based test. We identified a group of men with normal semen parameters but defective CatSper function. These men or couples failed to conceive naturally and upon medically assisted reproduction via intrauterine insemination and in vitro fertilization. Intracytoplasmic sperm injection (ICSI) was, ultimately, required to conceive a child. We revealed that the defective CatSper function was caused by variations in CATSPER genes. Moreover, we unveiled that CatSper-deficient human sperm were unable to undergo hyperactive motility and, therefore, failed to penetrate the egg coat. Thus, our study provides the experimental evidence that sperm hyperactivation is required for human fertilization, explaining the infertility of CatSper-deficient men and the need of ICSI for medically assisted reproduction. Finally, our study also revealed that defective CatSper function and ensuing failure to hyperactivate represents the most common cause of unexplained male infertility known thus far and that this sperm channelopathy can readily be diagnosed, enabling future evidence-based treatment of affected couples. The infertility of many couples rests on an enigmatic dysfunction of the man’s sperm. To gain insight into the underlying pathomechanisms, we assessed the function of the sperm-specific multisubunit CatSper-channel complex in the sperm of almost 2,300 men undergoing a fertility workup, using a simple motility-based test. We identified a group of men with normal semen parameters but defective CatSper function. These men or couples failed to conceive naturally and upon medically assisted reproduction via intrauterine insemination and in vitro fertilization. Intracytoplasmic sperm injection (ICSI) was, ultimately, required to conceive a child. We revealed that the defective CatSper function was caused by variations in CATSPER genes. Moreover, we unveiled that CatSper-deficient human sperm were unable to undergo hyperactive motility and, therefore, failed to penetrate the egg coat. Thus, our study provides the experimental evidence that sperm hyperactivation is required for human fertilization, explaining the infertility of CatSper-deficient men and the need of ICSI for medically assisted reproduction. Finally, our study also revealed that defective CatSper function and ensuing failure to hyperactivate represents the most common cause of unexplained male infertility known thus far and that this sperm channelopathy can readily be diagnosed, enabling future evidence-based treatment of affected couples. Defective CatSper function represents a common channelopathy affecting male fertility |
| Audience | Academic |
| Author | Brenker, Christoph Kliesch, Sabine Schlatt, Stefan Tüttelmann, Frank Wang, Tao Wagner, Alice Behre, Hermann M. Kierzek, Michelina Biagioni, Cristina Herrmann, Leonie Risse, Benjamin Nordhoff, Verena Hansen, Jan N. Krallmann, Claudia Stallmeyer, Birgit Strünker, Timo Wachten, Dagmar Haalck, Lars Deuster, Dirk Young, Samuel Potapenko, Anton Schiffer, Christian Patz, Jannika Pock, Tim Röpke, Albrecht |
| AuthorAffiliation | 6 Department of Phoniatrics and Pedaudiology, University Hospital Münster, University of Münster, Münster, Germany 7 Institute of Innate Immunity, Department of Biophysical Imaging, Medical Faculty, University of Bonn, Bonn, Germany 2 Institute of Reproductive Genetics 10 Cells in Motion Interfaculty Centre, University of Münster, Münster, Germany 4 CiM-IMPRS Graduate School 1 Centre of Reproductive Medicine and Andrology, University Hospital Münster, University of Münster, Münster, Germany 3 Institute of Human Genetics 5 Institute of Geoinformatics, Computer Vision and Machine Learning Systems, University of Münster, Münster, Germany 8 Computer Science Department, University of Münster, Münster, Germany 9 UKM Fertility Centre, University Hospital Münster, Münster, Germany |
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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/38165034$$D View this record in MEDLINE/PubMed |
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| Copyright | COPYRIGHT 2024 American Society for Clinical Investigation Copyright American Society for Clinical Investigation Jan 2024 2024 Young et al. 2024 Young et al. |
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| Keywords | Calcium channels Fertility Reproductive Biology Cell Biology |
| Language | English |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Authorship note: SY and CS are co–first authors. FT, C Brenker, and TS are co–last authors. DD is deceased. |
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| Snippet | The infertility of many couples rests on an enigmatic dysfunction of the man's sperm. To gain insight into the underlying pathomechanisms, we assessed the... The infertility of many couples rests on an enigmatic dysfunction of the man’s sperm. To gain insight into the underlying pathomechanisms, we assessed the... |
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| SubjectTerms | Biomedical research Calcium Channels - genetics Cell biology Channelopathy Child Evidence-based medicine Fertility Fertilization - physiology Fertilization in Vitro Genes Health aspects Humans In vitro fertilization Infertility Infertility, Male Infertility, Male - genetics Infertility, Male - therapy Male Men Methods Motility Patient outcomes Prevention Reproduction Reproductive biology Risk factors Semen - physiology Sperm Sperm Motility - physiology Spermatogenesis Spermatozoa - physiology |
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| Title | Human fertilization in vivo and in vitro requires the CatSper channel to initiate sperm hyperactivation |
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