Cfap97d1 is important for flagellar axoneme maintenance and male mouse fertility


Autoři: Seiya Oura aff001;  Samina Kazi aff002;  Audrey Savolainen aff002;  Kaori Nozawa aff003;  Julio Castañeda aff001;  Zhifeng Yu aff003;  Haruhiko Miyata aff001;  Ryan M. Matzuk aff003;  Jan N. Hansen aff005;  Dagmar Wachten aff005;  Martin M. Matzuk aff003;  Renata Prunskaite-Hyyryläinen aff002
Působiště autorů: Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan aff001;  Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland aff002;  Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas, United States of America aff003;  Center for Drug Discovery, Baylor College of Medicine, Houston, Texas, United States of America aff004;  Institute of Innate Immunity, Biophysical Imaging, Medical Faculty, University of Bonn, Bonn, Germany aff005
Vyšlo v časopise: Cfap97d1 is important for flagellar axoneme maintenance and male mouse fertility. PLoS Genet 16(8): e32767. doi:10.1371/journal.pgen.1008954
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008954

Souhrn

The flagellum is essential for sperm motility and fertilization in vivo. The axoneme is the main component of the flagella, extending through its entire length. An axoneme is comprised of two central microtubules surrounded by nine doublets, the nexin-dynein regulatory complex, radial spokes, and dynein arms. Failure to properly assemble components of the axoneme in a sperm flagellum, leads to fertility alterations. To understand this process in detail, we have defined the function of an uncharacterized gene, Cfap97 domain containing 1 (Cfap97d1). This gene is evolutionarily conserved in mammals and multiple other species, including Chlamydomonas. We have used two independently generated Cfap97d1 knockout mouse models to study the gene function in vivo. Cfap97d1 is exclusively expressed in testes starting from post-natal day 20 and continuing throughout adulthood. Deletion of the Cfap97d1 gene in both mouse models leads to sperm motility defects (asthenozoospermia) and male subfertility. In vitro fertilization (IVF) of cumulus-intact oocytes with Cfap97d1 deficient sperm yielded few embryos whereas IVF with zona pellucida-free oocytes resulted in embryo numbers comparable to that of the control. Knockout spermatozoa showed abnormal motility characterized by frequent stalling in the anti-hook position. Uniquely, Cfap97d1 loss caused a phenotype associated with axonemal doublet heterogeneity linked with frequent loss of the fourth doublet in the sperm stored in the epididymis. This study demonstrates that Cfap97d1 is required for sperm flagellum ultra-structure maintenance, thereby playing a critical role in sperm function and male fertility in mice.

Klíčová slova:

Flagella – Flagellar motility – Genetically modified animals – Heterozygosity – Microtubules – Mouse models – Sperm – Testes


Zdroje

1. Lindemann CB, Lesich KA. Functional anatomy of the mammalian sperm flagellum. Cytoskeleton (Hoboken) 2016 Nov;73(11):652–669.

2. Lindemann CB. Functional significance of the outer dense fibers of mammalian sperm examined by computer simulations with the geometric clutch model. Cell Motil Cytoskeleton 1996;34(4):258–270. doi: 10.1002/(SICI)1097-0169(1996)34:4<258::AID-CM1>3.0.CO;2-4 8871813

3. Loreng TD, Smith EF. The Central Apparatus of Cilia and Eukaryotic Flagella. Cold Spring Harb Perspect Biol 2017 Feb 1;9(2): doi: 10.1101/cshperspect.a028118 27770014

4. Inaba K. Sperm flagella: comparative and phylogenetic perspectives of protein components. Mol Hum Reprod 2011 Aug;17(8):524–538. doi: 10.1093/molehr/gar034 21586547

5. Mohri H, Inaba K, Ishijima S, Baba SA. Tubulin-dynein system in flagellar and ciliary movement. Proc Jpn Acad Ser B Phys Biol Sci 2012;88(8):397–415. doi: 10.2183/pjab.88.397 23060230

6. Smith EF, Lefebvre PA. The role of central apparatus components in flagellar motility and microtubule assembly. Cell Motil Cytoskeleton 1997;38(1):1–8. doi: 10.1002/(SICI)1097-0169(1997)38:1<1::AID-CM1>3.0.CO;2-C 9295136

7. Friedrich BM, Riedel-Kruse IH, Howard J, Julicher F. High-precision tracking of sperm swimming fine structure provides strong test of resistive force theory. J Exp Biol 2010 Apr;213(Pt 8):1226–1234. doi: 10.1242/jeb.039800 20348333

8. Wang S, Larina IV. In vivo three-dimensional tracking of sperm behaviors in the mouse oviduct. Development 2018 Mar 19;145(6): doi: 10.1242/dev.157685 29487107

9. Curi SM, Ariagno JI, Chenlo PH, Mendeluk GR, Pugliese MN, Sardi Segovia LM, et al. Asthenozoospermia: analysis of a large population. Arch Androl 2003 Sep-Oct;49(5):343–349. doi: 10.1080/01485010390219656 12893510

10. Matsumoto AM, Bremner WJ. Textbook of Endocrinology. 2016:694–784.

11. Matzuk MM, Lamb DJ. The biology of infertility: research advances and clinical challenges. Nat Med 2008 Nov;14(11):1197–1213. doi: 10.1038/nm.f.1895 18989307

12. Roy A, Lin YN, Agno JE, DeMayo FJ, Matzuk MM. Absence of tektin 4 causes asthenozoospermia and subfertility in male mice. FASEB J 2007 Apr;21(4):1013–1025. doi: 10.1096/fj.06-7035com 17244819

13. Castaneda JM, Hua R, Miyata H, Oji A, Guo Y, Cheng Y, et al. TCTE1 is a conserved component of the dynein regulatory complex and is required for motility and metabolism in mouse spermatozoa. Proc Natl Acad Sci U S A 2017 July 03;114(27):E5378.

14. Schultz N, Hamra FK, Garbers DL. A multitude of genes expressed solely in meiotic or postmeiotic spermatogenic cells offers a myriad of contraceptive targets. Proc Natl Acad Sci U S A 2003 Oct 14;100(21):12201–12206. doi: 10.1073/pnas.1635054100 14526100

15. Djureinovic D, Fagerberg L, Hallstrom B, Danielsson A, Lindskog C, Uhlen M, et al. The human testis-specific proteome defined by transcriptomics and antibody-based profiling. Mol Hum Reprod 2014 Jun;20(6):476–488. doi: 10.1093/molehr/gau018 24598113

16. Uhlen M, Fagerberg L, Hallstrom BM, Lindskog C, Oksvold P, Mardinoglu A, et al. Proteomics. Tissue-based map of the human proteome. Science 2015 Jan 23;347(6220):1260419. doi: 10.1126/science.1260419 25613900

17. Pazour GJ, Agrin N, Leszyk J, Witman GB. Proteomic analysis of a eukaryotic cilium. J Cell Biol 2005 Jul 4;170(1):103–113. doi: 10.1083/jcb.200504008 15998802

18. Gupta GD, Coyaud E, Goncalves J, Mojarad BA, Liu Y, Wu Q, et al. A Dynamic Protein Interaction Landscape of the Human Centrosome-Cilium Interface. Cell 2015 Dec 3;163(6):1484–1499. doi: 10.1016/j.cell.2015.10.065 26638075

19. Soulavie F, Piepenbrock D, Thomas J, Vieillard J, Duteyrat JL, Cortier E, et al. hemingway is required for sperm flagella assembly and ciliary motility in Drosophila. Mol Biol Cell 2014 Apr;25(8):1276–1286. doi: 10.1091/mbc.E13-10-0616 24554765

20. Noda T, Sakurai N, Nozawa K, Kobayashi S, Devlin DJ, Matzuk MM, et al. Nine genes abundantly expressed in the epididymis are not essential for male fecundity in mice. Andrology 2019 Mar 29.

21. Takeo T, Nakagata N. Reduced glutathione enhances fertility of frozen/thawed C57BL/6 mouse sperm after exposure to methyl-beta-cyclodextrin. Biol Reprod 2011 Nov;85(5):1066–1072. doi: 10.1095/biolreprod.111.092536 21778138

22. Takeo T, Nakagata N. In Vitro Fertilization in Mice. Cold Spring Harb Protoc 2018 Jun 1;2018(6): doi: 10.1101/pdb.prot094524. 29669849

23. Miyata H, Satouh Y, Mashiko D, Muto M, Nozawa K, Shiba K, et al. Sperm calcineurin inhibition prevents mouse fertility with implications for male contraceptive. Science 2015 October 23;350(6259):442–445. doi: 10.1126/science.aad0836 26429887

24. Ren D, Navarro B, Perez G, Jackson AC, Hsu S, Shi Q, et al. A sperm ion channel required for sperm motility and male fertility. Nature 2001 Oct 11;413(6856):603–609. doi: 10.1038/35098027 11595941

25. Visconti PE, Bailey JL, Moore GD, Pan D, Olds-Clarke P, Kopf GS. Capacitation of mouse spermatozoa. I. Correlation between the capacitation state and protein tyrosine phosphorylation. Development 1995 Apr;121(4):1129–1137. 7743926

26. Visconti PE, Moore GD, Bailey JL, Leclerc P, Connors SA, Pan D, et al. Capacitation of mouse spermatozoa. II. Protein tyrosine phosphorylation and capacitation are regulated by a cAMP-dependent pathway. Development 1995 Apr;121(4):1139–1150. 7538069

27. Lindemann CB, Lesich KA. Flagellar and ciliary beating: the proven and the possible. J Cell Sci 2010 Feb 15;123(Pt 4):519–528. doi: 10.1242/jcs.051326 20145000

28. Curry AM, Williams BD, Rosenbaum JL. Sequence analysis reveals homology between two proteins of the flagellar radial spoke. Mol Cell Biol 1992 Sep;12(9):3967–3977. doi: 10.1128/mcb.12.9.3967 1508197

29. Truebestein L, Leonard TA. Coiled-coils: The long and short of it. Bioessays 2016 Sep;38(9):903–916. doi: 10.1002/bies.201600062 27492088

30. Abbasi F, Miyata H, Shimada K, Morohoshi A, Nozawa K, Matsumura T, et al. RSPH6A is required for sperm flagellum formation and male fertility in mice. J Cell Sci 2018 Oct 11;131(19): doi: 10.1242/jcs.221648 30185526

31. Paudel B, Gervasi MG, Porambo J, Caraballo DA, Tourzani DA, Mager J, et al. Sperm capacitation is associated with phosphorylation of the testis-specific radial spoke protein Rsph6adagger. Biol Reprod 2019 Feb 1;100(2):440–454. doi: 10.1093/biolre/ioy202 30239614

32. Lin J, Tritschler D, Song K, Barber CF, Cobb JS, Porter ME, et al. Building blocks of the nexin-dynein regulatory complex in Chlamydomonas flagella. J Biol Chem 2011 Aug 19;286(33):29175–29191. doi: 10.1074/jbc.M111.241760 21700706

33. Gui L, Song K, Tritschler D, Bower R, Yan S, Dai A, et al. Scaffold subunits support associated subunit assembly in the Chlamydomonas ciliary nexin-dynein regulatory complex. Proc Natl Acad Sci U S A 2019 Nov 12;116(46):23152–23162. doi: 10.1073/pnas.1910960116 31659045

34. Morohoshi A, Miyata H, Shimada K, Nozawa K, Matsumura T, Yanase R, et al. Nexin-Dynein regulatory complex component DRC7 but not FBXL13 is required for sperm flagellum formation and male fertility in mice. PLoS Genet 2020 Jan 21;16(1):e1008585. doi: 10.1371/journal.pgen.1008585 31961863

35. Bernstein M, Beech PL, Katz SG, Rosenbaum JL. A new kinesin-like protein (Klp1) localized to a single microtubule of the Chlamydomonas flagellum. J Cell Biol 1994 Jun;125(6):1313–1326. doi: 10.1083/jcb.125.6.1313 8207060

36. Demonchy R, Blisnick T, Deprez C, Toutirais G, Loussert C, Marande W, et al. Kinesin 9 family members perform separate functions in the trypanosome flagellum. J Cell Biol 2009 Nov 30;187(5):615–622. doi: 10.1083/jcb.200903139 19948486

37. Yokoyama R O'toole E, Ghosh S, Mitchell DR. Regulation of flagellar dynein activity by a central pair kinesin. Proc Natl Acad Sci U S A 2004 Dec 14;101(50):17398–17403. doi: 10.1073/pnas.0406817101 15572440

38. Miyata H, Shimada K, Morohoshi A, Oura S, Matsumura T, Xu Z, et al. Testis-enriched kinesin KIF9 is important for progressive motility in mouse spermatozoa. FASEB J 2020 Apr;34(4):5389–5400. doi: 10.1096/fj.201902755R 32072696

39. Fujihara Y, Miyata H, Ikawa M. Factors controlling sperm migration through the oviduct revealed by gene-modified mouse models. Exp Anim 2018 May 10;67(2):91–104. doi: 10.1538/expanim.17-0153 29353867

40. Hino T, Yanagimachi R. Active peristaltic movements and fluid production of the mouse oviduct: their roles in fluid and sperm transport and fertilizationdagger. Biol Reprod 2019 Jul 1;101(1):40–49. doi: 10.1093/biolre/ioz061 30977810

41. Rosenbaum JL, Witman GB. Intraflagellar transport. Nat Rev Mol Cell Biol 2002 Nov;3(11):813–825. doi: 10.1038/nrm952 12415299

42. Scholey JM. Intraflagellar transport motors in cilia: moving along the cell's antenna. J Cell Biol 2008 Jan 14;180(1):23–29. doi: 10.1083/jcb.200709133 18180368

43. Merlino GT, Stahle C, Jhappan C, Linton R, Mahon KA, Willingham MC. Inactivation of a sperm motility gene by insertion of an epidermal growth factor receptor transgene whose product is overexpressed and compartmentalized during spermatogenesis. Genes Dev 1991 Aug;5(8):1395–1406. doi: 10.1101/gad.5.8.1395 1714416

44. Sampson MJ, Decker WK, Beaudet AL, Ruitenbeek W, Armstrong D, Hicks MJ, et al. Immotile sperm and infertility in mice lacking mitochondrial voltage-dependent anion channel type 3. J Biol Chem 2001 Oct 19;276(42):39206–39212. doi: 10.1074/jbc.M104724200 11507092

45. Konno A, Ikegami K, Konishi Y, Yang HJ, Abe M, Yamazaki M, et al. Ttll9-/- mice sperm flagella show shortening of doublet 7, reduction of doublet 5 polyglutamylation and a stall in beating. J Cell Sci 2016 Jul 15;129(14):2757–2766. doi: 10.1242/jcs.185983 27257088

46. Sato H, Taketomi Y, Isogai Y, Miki Y, Yamamoto K, Masuda S, et al. Group III secreted phospholipase A2 regulates epididymal sperm maturation and fertility in mice. J Clin Invest 2010 May;120(5):1400–1414. doi: 10.1172/JCI40493 20424323

47. Zhang B, Ma H, Khan T, Ma A, Li T, Zhang H, et al. A DNAH17 missense variant causes flagella destabilization and asthenozoospermia. J Exp Med 2020 Feb 3;217(2): doi: 10.1084/jem.20182365 31658987

48. Olbrich H, Schmidts M, Werner C, Onoufriadis A, Loges NT, Raidt J, et al. Recessive HYDIN mutations cause primary ciliary dyskinesia without randomization of left-right body asymmetry. Am J Hum Genet 2012 Oct 5;91(4):672–684. doi: 10.1016/j.ajhg.2012.08.016 23022101

49. McKenzie CW, Craige B, Kroeger TV, Finn R, Wyatt TA, Sisson JH, et al. CFAP54 is required for proper ciliary motility and assembly of the central pair apparatus in mice. Mol Biol Cell 2015 Sep 15;26(18):3140–3149. doi: 10.1091/mbc.E15-02-0121 26224312

50. Oura S, Miyata H, Noda T, Shimada K, Matsumura T, Morohoshi A, et al. Chimeric analysis with newly established EGFP/DsRed2-tagged ES cells identify HYDIN as essential for spermiogenesis in mice. Exp Anim 2019 Feb 26;68(1):25–34. doi: 10.1538/expanim.18-0071 30089752

51. Tang S, Wang X, Li W, Yang X, Li Z, Liu W, et al. Biallelic Mutations in CFAP43 and CFAP44 Cause Male Infertility with Multiple Morphological Abnormalities of the Sperm Flagella. Am J Hum Genet 2017 Jun 1;100(6):854–864. doi: 10.1016/j.ajhg.2017.04.012 28552195

52. Dong FN, Amiri-Yekta A, Martinez G, Saut A, Tek J, Stouvenel L, et al. Absence of CFAP69 Causes Male Infertility due to Multiple Morphological Abnormalities of the Flagella in Human and Mouse. Am J Hum Genet 2018 Apr 5;102(4):636–648. doi: 10.1016/j.ajhg.2018.03.007 29606301

53. Coutton C, Escoffier J, Martinez G, Arnoult C, Ray PF. Teratozoospermia: spotlight on the main genetic actors in the human. Hum Reprod Update 2015 Jul-Aug;21(4):455–485. doi: 10.1093/humupd/dmv020 25888788

54. Ben Khelifa M, Coutton C, Zouari R, Karaouzene T, Rendu J, Bidart M, et al. Mutations in DNAH1, which encodes an inner arm heavy chain dynein, lead to male infertility from multiple morphological abnormalities of the sperm flagella. Am J Hum Genet 2014 Jan 2;94(1):95–104. doi: 10.1016/j.ajhg.2013.11.017 24360805

55. Merveille AC, Davis EE, Becker-Heck A, Legendre M, Amirav I, Bataille G, et al. CCDC39 is required for assembly of inner dynein arms and the dynein regulatory complex and for normal ciliary motility in humans and dogs. Nat Genet 2011 Jan;43(1):72–78. doi: 10.1038/ng.726 21131972

56. Shen Y, Zhang F, Li F, Jiang X, Yang Y, Li X, et al. Loss-of-function mutations in QRICH2 cause male infertility with multiple morphological abnormalities of the sperm flagella. Nat Commun 2019 Jan 25;doi: 10(1):433-018-08182-x

57. Wang WL, Tu CF, Tan YQ. Insight on multiple morphological abnormalities of sperm flagella in male infertility: what is new? Asian J Androl 2019 Jun 14.

58. Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, et al. A conditional knockout resource for the genome-wide study of mouse gene function. Nature 2011 Jun 15;474(7351):337–342. doi: 10.1038/nature10163 21677750

59. Ho Y, Wigglesworth K, Eppig JJ, Schultz RM. Preimplantation development of mouse embryos in KSOM: augmentation by amino acids and analysis of gene expression. Mol Reprod Dev 1995 Jun;41(2):232–238. doi: 10.1002/mrd.1080410214 7654376

60. Prunskaite-Hyyrylainen R, Shan J, Railo A, Heinonen KM, Miinalainen I, Yan W, et al. Wnt4, a pleiotropic signal for controlling cell polarity, basement membrane integrity, and antimullerian hormone expression during oocyte maturation in the female follicle. FASEB J 2014 Apr;28(4):1568–1581. doi: 10.1096/fj.13-233247 24371124

61. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 2001 Dec;25(4):402–408. doi: 10.1006/meth.2001.1262 11846609

62. Prunskaite-Hyyrylainen R, Skovorodkin I, Xu Q, Miinalainen I, Shan J, Vainio SJ. Wnt4 coordinates directional cell migration and extension of the Mullerian duct essential for ontogenesis of the female reproductive tract. Hum Mol Genet 2016 Mar 15;25(6):1059–1073. doi: 10.1093/hmg/ddv621 26721931

63. Toyoda Y, Yokoyama M, Hoshi T. Studies on the fertilization of mouse eggs in vitro. Jpn J Anim Reprod 1971;16:147–151.

64. Ikawa M, Tokuhiro K, Yamaguchi R, Benham AM, Tamura T, Wada I, et al. Calsperin is a testis-specific chaperone required for sperm fertility. J Biol Chem 2011 Feb 18;286(7):5639–5646. doi: 10.1074/jbc.M110.140152 21131354

65. Tokuhiro K, Ikawa M, Benham AM, Okabe M. Protein disulfide isomerase homolog PDILT is required for quality control of sperm membrane protein ADAM3 and male fertility [corrected. Proc Natl Acad Sci U S A 2012 Mar 6;109(10):3850–3855. doi: 10.1073/pnas.1117963109 22357757

66. Kimura Y, Yanagimachi R. Development of normal mice from oocytes injected with secondary spermatocyte nuclei. Biol Reprod 1995 Oct;53(4):855–862. doi: 10.1095/biolreprod53.4.855 8547481

67. Hansen JN, Rassmann S, Jikeli JF, Wachten D. SpermQ(-) A Simple Analysis Software to Comprehensively Study Flagellar Beating and Sperm Steering. Cells 2018 Dec 26;8(1): doi: 10.3390/cells8010010 30587820

68. Bjorkgren I, Alvarez L, Blank N, Balbach M, Turunen H, Laajala TD, et al. Targeted inactivation of the mouse epididymal beta-defensin 41 alters sperm flagellar beat pattern and zona pellucida binding. Mol Cell Endocrinol 2016 May 15;427:143–154. doi: 10.1016/j.mce.2016.03.013 26987518


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