دورية أكاديمية
Inherited defects of piRNA biogenesis cause transposon de-repression, impaired spermatogenesis, and human male infertility.
العنوان: | Inherited defects of piRNA biogenesis cause transposon de-repression, impaired spermatogenesis, and human male infertility. |
---|---|
المؤلفون: | Stallmeyer B; Centre of Medical Genetics, Institute of Reproductive Genetics, University of Münster, Münster, Germany., Bühlmann C; Centre of Medical Genetics, Institute of Reproductive Genetics, University of Münster, Münster, Germany., Stakaitis R; Division of Genetics, Oregon National Primate Research Center, Oregon Health & Science University, Portland, OR, USA.; Laboratory of Molecular Neurooncology, Neuroscience Institute, Lithuanian University of Health Sciences, Kaunas, Lithuania., Dicke AK; Centre of Medical Genetics, Institute of Reproductive Genetics, University of Münster, Münster, Germany., Ghieh F; Centre of Medical Genetics, Institute of Reproductive Genetics, University of Münster, Münster, Germany., Meier L; Centre of Medical Genetics, Institute of Reproductive Genetics, University of Münster, Münster, Germany., Zoch A; Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh, UK.; Wellcome Centre for Cell Biology, School of Biological Sciences, The University of Edinburgh, Edinburgh, UK., MacKenzie MacLeod D; Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh, UK.; Wellcome Centre for Cell Biology, School of Biological Sciences, The University of Edinburgh, Edinburgh, UK., Steingröver J; Centre of Medical Genetics, Institute of Reproductive Genetics, University of Münster, Münster, Germany., Okutman Ö; Laboratoire de Génétique Médicale LGM, institut de génétique médicale d'Alsace IGMA, INSERM UMR 1112, Université de Strasbourg, Strasbourg, France.; Hôpital Universitaire de Bruxelles, Hôpital Erasme, Service de Gynécologie-Obstétrique, Clinique de Fertilité, Université libre de Bruxelles (ULB), Bruxelles, Belgium., Fietz D; Institute of Veterinary Anatomy, Histology and Embryology, Justus-Liebig-Universität Gießen, Gießen, Germany., Pilatz A; Clinic for Urology, Paediatric Urology and Andrology, Justus Liebig University Gießen, Gießen, Germany., Riera-Escamilla A; Andrology Department, Fundació Puigvert, Universitat Autònoma de Barcelona, Instituto de Investigaciones Biomédicas Sant Pau, Barcelona, Catalonia, Spain., Xavier MJ; Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK., Ruckert C; Centre of Medical Genetics, Department of Medical Genetics, University of Münster, Münster, Germany., Di Persio S; Centre of Reproductive Medicine and Andrology, Department of Clinical and Surgical Andrology, University Hospital Münster, Münster, Germany., Neuhaus N; Centre of Reproductive Medicine and Andrology, Department of Clinical and Surgical Andrology, University Hospital Münster, Münster, Germany., Gurbuz AS; Department of Gynecology and Obstetrics Novafertil IVF Center, Konya, Turkey., Şalvarci A; Department of Andrology Novafertil IVF Center, Konya, Turkey., Le May N; Laboratoire de Génétique Médicale LGM, institut de génétique médicale d'Alsace IGMA, INSERM UMR 1112, Université de Strasbourg, Strasbourg, France., McEleny K; Newcastle Fertility Centre, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK., Friedrich C; Centre of Medical Genetics, Institute of Reproductive Genetics, University of Münster, Münster, Germany., van der Heijden G; Department of Obstetrics and Gynecology, Radboud University Medical Center, Nijmegen, The Netherlands., Wyrwoll MJ; Centre of Medical Genetics, Institute of Reproductive Genetics, University of Münster, Münster, Germany.; Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh, UK., Kliesch S; Centre of Reproductive Medicine and Andrology, Department of Clinical and Surgical Andrology, University Hospital Münster, Münster, Germany., Veltman JA; Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK., Krausz C; Andrology Department, Fundació Puigvert, Universitat Autònoma de Barcelona, Instituto de Investigaciones Biomédicas Sant Pau, Barcelona, Catalonia, Spain.; Department of Experimental and Clinical Biomedical Sciences 'Mario Serio', University of Florence, University Hospital Careggi, Florence, Italy., Viville S; Laboratoire de Génétique Médicale LGM, institut de génétique médicale d'Alsace IGMA, INSERM UMR 1112, Université de Strasbourg, Strasbourg, France.; Laboratoire de Diagnostic Génétique, UF3472-génétique de l'infertilité, Hôpitaux Universitaires de Strasbourg, Strasbourg, France., Conrad DF; Division of Genetics, Oregon National Primate Research Center, Oregon Health & Science University, Portland, OR, USA., O'Carroll D; Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh, UK.; Wellcome Centre for Cell Biology, School of Biological Sciences, The University of Edinburgh, Edinburgh, UK., Tüttelmann F; Centre of Medical Genetics, Institute of Reproductive Genetics, University of Münster, Münster, Germany. frank.tuettelmann@ukmuenster.de. |
المصدر: | Nature communications [Nat Commun] 2024 Aug 09; Vol. 15 (1), pp. 6637. Date of Electronic Publication: 2024 Aug 09. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: [London] : Nature Pub. Group |
مواضيع طبية MeSH: | Spermatogenesis*/genetics , Infertility, Male*/genetics , Infertility, Male*/metabolism , Infertility, Male*/pathology , RNA, Small Interfering*/metabolism , RNA, Small Interfering*/genetics , DNA Transposable Elements*/genetics , Testis*/metabolism, Male ; Humans ; Animals ; Mice ; Adult ; Gene Silencing ; Mice, Knockout ; Argonaute Proteins/metabolism ; Argonaute Proteins/genetics ; Long Interspersed Nucleotide Elements/genetics ; Spermatogonia/metabolism ; DEAD-box RNA Helicases/genetics ; DEAD-box RNA Helicases/metabolism ; Piwi-Interacting RNA |
مستخلص: | piRNAs are crucial for transposon silencing, germ cell maturation, and fertility in male mice. Here, we report on the genetic landscape of piRNA dysfunction in humans and present 39 infertile men carrying biallelic variants in 14 different piRNA pathway genes, including PIWIL1, GTSF1, GPAT2, MAEL, TDRD1, and DDX4. In some affected men, the testicular phenotypes differ from those of the respective knockout mice and range from complete germ cell loss to the production of a few morphologically abnormal sperm. A reduced number of pachytene piRNAs was detected in the testicular tissue of variant carriers, demonstrating impaired piRNA biogenesis. Furthermore, LINE1 expression in spermatogonia links impaired piRNA biogenesis to transposon de-silencing and serves to classify variants as functionally relevant. These results establish the disrupted piRNA pathway as a major cause of human spermatogenic failure and provide insights into transposon silencing in human male germ cells. (© 2024. The Author(s).) |
References: | Science. 2007 May 4;316(5825):744-7. (PMID: 17446352) Protein Sci. 2022 Jan;31(1):8-22. (PMID: 34717010) Commun Biol. 2023 Mar 31;6(1):350. (PMID: 36997603) Hum Reprod Update. 2022 Nov 2;28(6):763-797. (PMID: 35613017) JAMA. 2013 Nov 27;310(20):2191-4. (PMID: 24141714) Mamm Genome. 2022 Jun;33(2):293-311. (PMID: 34724117) Nat Commun. 2017 Oct 10;8(1):819. (PMID: 29018194) Cell Res. 2014 Jun;24(6):680-700. (PMID: 24787618) Dev Biol. 2009 Nov 1;335(1):216-27. (PMID: 19735653) Nat Cell Biol. 2021 Sep;23(9):1013-1022. (PMID: 34489574) Nat Commun. 2020 Feb 12;11(1):858. (PMID: 32051406) PLoS Genet. 2009 Sep;5(9):e1000635. (PMID: 19730684) Mol Cell. 2012 Sep 28;47(6):970-9. (PMID: 22902560) Eur Urol. 2023 May;83(5):452-462. (PMID: 35690514) J Med Genet. 2017 Sep;54(9):633-639. (PMID: 28536242) Genes Dev. 2015 May 15;29(10):1032-44. (PMID: 25995188) Genet Med. 2020 Dec;22(12):1967-1975. (PMID: 32719396) Am J Hum Genet. 2022 Mar 3;109(3):508-517. (PMID: 35172124) Nature. 2011 Oct 23;480(7376):259-63. (PMID: 22020280) Genome Biol. 2009;10(3):R25. (PMID: 19261174) Proc Natl Acad Sci U S A. 2010 Jun 29;107(26):11847-52. (PMID: 20547853) J Reprod Fertil. 1995 Sep;105(1):25-33. (PMID: 7490711) Genome Med. 2020 Jul 14;12(1):62. (PMID: 32664994) Mol Cell. 2013 May 23;50(4):601-8. (PMID: 23706823) Nat Struct Mol Biol. 2017 Jul;24(7):604-606. (PMID: 28530707) Bioinformatics. 2010 Mar 1;26(5):589-95. (PMID: 20080505) Nature. 2020 Aug;584(7822):635-639. (PMID: 32674113) Nat Methods. 2022 Jun;19(6):679-682. (PMID: 35637307) Genome Biol. 2016 Jun 06;17(1):122. (PMID: 27268795) Hum Reprod. 2022 May 30;37(6):1334-1350. (PMID: 35413094) Genome Res. 2010 Sep;20(9):1297-303. (PMID: 20644199) RNA. 2013 Jun;19(6):803-10. (PMID: 23611983) Mol Cell. 2008 Sep 26;31(6):785-99. (PMID: 18922463) EMBO J. 2014 Sep 17;33(18):1999-2019. (PMID: 25063675) Cell. 2021 Apr 15;184(8):1941-1942. (PMID: 33861957) Nat Rev Mol Cell Biol. 2023 Feb;24(2):123-141. (PMID: 36104626) Mol Cell. 2024 Mar 21;84(6):1021-1035.e11. (PMID: 38359823) Dev Cell. 2011 Mar 15;20(3):376-87. (PMID: 21397848) Genes Dev. 2015 Mar 15;29(6):617-29. (PMID: 25762440) Nat Struct Mol Biol. 2012 Aug;19(8):773-81. (PMID: 22842725) Nature. 2006 Jul 13;442(7099):203-7. (PMID: 16751777) PLoS Genet. 2023 Nov 13;19(11):e1011031. (PMID: 37956204) Nature. 2011 Nov 27;480(7376):264-7. (PMID: 22121019) Proc Natl Acad Sci U S A. 2013 Oct 8;110(41):16492-7. (PMID: 24067652) Nat Commun. 2023 Aug 29;14(1):5267. (PMID: 37644029) Nat Genet. 2000 May;25(1):25-9. (PMID: 10802651) Cell. 2019 Dec 12;179(7):1566-1581.e16. (PMID: 31835033) Cell Res. 2017 Nov;27(11):1392-1396. (PMID: 28994417) Nat Methods. 2020 Mar;17(3):261-272. (PMID: 32015543) Nature. 2021 Aug;596(7873):583-589. (PMID: 34265844) Cell. 2017 Jun 1;169(6):1090-1104.e13. (PMID: 28552346) Crit Rev Biochem Mol Biol. 2019 Apr;54(2):119-132. (PMID: 31046474) Nature. 2020 Feb;578(7794):311-316. (PMID: 31996847) Am J Hum Genet. 2022 Oct 6;109(10):1850-1866. (PMID: 36150389) PLoS One. 2011;6(7):e21800. (PMID: 21789182) Genes Dev. 2000 Apr 1;14(7):841-53. (PMID: 10766740) PLoS One. 2017 May 17;12(5):e0177097. (PMID: 28520746) Bioinformatics. 2019 Mar 15;35(6):1033-1039. (PMID: 30668832) Mol Cell. 2013 Apr 11;50(1):67-81. (PMID: 23523368) Nat Rev Genet. 2019 Feb;20(2):89-108. (PMID: 30446728) PLoS Genet. 2009 Dec;5(12):e1000764. (PMID: 20011505) Dev Cell. 2009 Dec;17(6):775-87. (PMID: 20059948) Dev Cell. 2002 Jun;2(6):819-30. (PMID: 12062093) N Engl J Med. 2021 Aug 19;385(8):707-719. (PMID: 34347949) Nat Protoc. 2019 Mar;14(3):703-721. (PMID: 30804569) Histochem Cell Biol. 2013 Aug;140(2):169-81. (PMID: 23412502) Cells Tissues Organs. 2012;196(6):543-54. (PMID: 22739409) Dev Cell. 2008 Aug;15(2):285-97. (PMID: 18694567) Genes Dev. 2010 May;24(9):887-92. (PMID: 20439430) Nat Ecol Evol. 2020 Jan;4(1):156-168. (PMID: 31900453) Sci Adv. 2021 Jul 28;7(31):. (PMID: 34321199) Proc Natl Acad Sci U S A. 2006 Oct 24;103(43):15894-9. (PMID: 17038506) Genetics. 2023 May 4;224(1):. (PMID: 36866529) Development. 2004 Feb;131(4):839-49. (PMID: 14736746) PLoS Genet. 2015 Oct 23;11(10):e1005620. (PMID: 26496356) Biol Reprod. 2019 Jul 1;101(1):248-256. (PMID: 30951587) Nat Commun. 2022 Dec 26;13(1):7953. (PMID: 36572685) Nat Commun. 2022 Jan 10;13(1):154. (PMID: 35013161) Nature. 2006 Jul 13;442(7099):199-202. (PMID: 16751776) Dev Cell. 2011 Mar 15;20(3):364-75. (PMID: 21397847) Stem Cell Res. 2020 Jan;42:101703. (PMID: 32006804) Nature. 2022 Aug;608(7923):618-625. (PMID: 35772669) Gene. 2008 Dec 31;427(1-2):104-10. (PMID: 18930792) Genet Med. 2020 Dec;22(12):1956-1966. (PMID: 32741963) Genes Dev. 2008 Apr 1;22(7):908-17. (PMID: 18381894) BMC Bioinformatics. 2019 Feb 18;20(1):84. (PMID: 30777018) |
معلومات مُعتمدة: | CRU326, 329621271 Deutsche Forschungsgemeinschaft (German Research Foundation); 01GR2303 Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research); 01GR2303 Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research) |
المشرفين على المادة: | 0 (RNA, Small Interfering) 0 (DNA Transposable Elements) 0 (Argonaute Proteins) EC 3.6.4.13 (DEAD-box RNA Helicases) 0 (PIWIL1 protein, human) 0 (Piwi-Interacting RNA) |
تواريخ الأحداث: | Date Created: 20240809 Date Completed: 20240809 Latest Revision: 20240812 |
رمز التحديث: | 20240813 |
مُعرف محوري في PubMed: | PMC11316121 |
DOI: | 10.1038/s41467-024-50930-9 |
PMID: | 39122675 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2041-1723 |
---|---|
DOI: | 10.1038/s41467-024-50930-9 |