Abstract
The acrosome, a single exocytotic vesicle on the head of sperm, has an essential role in fertilization, but the exact mechanisms by which it facilitates sperm–egg interactions remain unresolved. The acrosome contains dozens of secretory proteins that are packaged into the forming structure during spermatogenesis; many of these proteins are localized into specific topographical areas of the acrosome, while others are more diffusely distributed. Acrosomal proteins can also be biochemically classified as components of the acrosomal matrix, a large, relatively insoluble complex, or as soluble proteins. This review focuses on recent findings using genetically modified mice (gene knockouts and transgenic “green acrosome” mice) to study the effects of eliminating acrosomal matrix-associated proteins on sperm structure and function. Some gene knockouts produce infertile phenotypes with obviously missing, specific activities that affect acrosome biogenesis during spermatogenesis or interfere with acrosome function in mature sperm. Mutations that delete some components produce fertile phenotypes with subtler effects that provide useful insights into acrosomal matrix function in fertilization. In general, these studies enable the reassessment of paradigms to explain acrosome formation and function and provide novel, objective insights into the roles of acrosomal matrix proteins in fertilization. The use of genetically engineered mouse models has yielded new mechanistic information that complements recent, important in vivo imaging studies.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Adham IM, Nayernia K, Engel W (1997) Spermatozoa lacking acrosin protein show delayed fertilization. Mol Reprod Dev 46:370–376. doi:10.1002/(SICI)1098-2795(199703)46:<370::AID-MRD16>3.0.CO;2-2
Anakwe OO, Gerton GL (1990) Acrosome biogenesis begins during meiosis: Evidence from the synthesis and distribution of an acrosomal glycoprotein, acrogranin, during guinea pig spermatogenesis. Biol Reprod 42:317–328
Anakwe OO, Sharma S, Hoff HB et al (1991) Maturation of guinea pig sperm in the epididymis involves the modification of proacrosin oligosaccharide side chains. Mol Reprod Dev 29:294–301. doi:10.1002/mrd.1080290313
Arimitsu N, Kogure T, Baba T et al (2011) p125/Sec23-interacting protein (Sec23ip) is required for spermiogenesis. FEBS Lett 585:2171–2176. doi:10.1016/j.febslet.2011.05.050
Baba T, Azuma S, Kashiwabara S, Toyoda Y (1994) Sperm from mice carrying a targeted mutation of the acrosin gene can penetrate the oocyte zona pellucida and effect fertilization. J Biol Chem 269:31845–31849
Baba D, Kashiwabara S, Honda A et al (2002) Mouse sperm lacking cell surface hyaluronidase PH-20 can pass through the layer of cumulus cells and fertilize the egg. J Biol Chem 277:30310–30314. doi:10.1074/jbc.M204596200
Bedford JM (1998) Mammalian fertilization misread? Sperm penetration of the eutherian zona pellucida is unlikely to be a lytic event. Biol Reprod 59:1275–1287. doi:10.1095/biolreprod59.6.1275
Bi M, Hickox JR, Winfrey VP et al (2003) Processing, localization and binding activity of zonadhesin suggest a function in sperm adhesion to the zona pellucida during exocytosis of the acrosome. Biochem J 375:477–488. doi:10.1042/bj20030753
Bjartmar L, Huberman AD, Ullian EM et al (2006) Neuronal pentraxins mediate synaptic refinement in the developing visual system. J Neurosci 26:6269–6281. doi:10.1523/JNEUROSCI.4212-05.2006
Bleil JD, Wassarman PM (1990) Identification of a ZP3-binding protein on acrosome-intact mouse sperm by photoaffinity crosslinking. Proc Natl Acad Sci 87:5563–5567
Bloom W, Fawcett DW, Maximow AA (1975) A textbook of histology, 10th edn. Saunders, Philadelphia
Bookbinder LH, Cheng A, Bleil JD (1995) Tissue- and species-specific expression of sp56, a mouse sperm fertilization protein. Science 269:86–89
Buffone MG, Foster JA, Gerton GL (2008) The role of the acrosomal matrix in fertilization. Int J Dev Biol 52:511–522. doi:10.1387/ijdb.072532mb
Buffone MG, Kim K-S, Doak BJ et al (2009) Functional consequences of cleavage, dissociation and exocytotic release of ZP3R, a C4BP-related protein, from the mouse sperm acrosomal matrix. J Cell Sci 122:3153–3160. doi:10.1242/jcs.052977
Cheng A, Le T, Palacios M et al (1994) Sperm-egg recognition in the mouse: Characterization of sp56, a sperm protein having specific affinity for ZP3. J Cell Biol 125:867–878
Fawcett DW, Hollenberg RD (1963) Changes in the acrosome of the guinea pig spermatozoa during passage through the epididymis. Z Zellforsch Mikrosk Anat 60:276–292
Fléchon J-E (2015) The acrosome of eutherian mammals. Cell Tissue Res 363:147–157. doi: 10.1007/s00441-015-2238-0
Foster JA, Friday BB, Maulit MT et al (1997) AM67, a secretory component of the guinea pig sperm acrosomal matrix, is related to mouse sperm protein sp56 and the complement component 4-binding proteins. J Biol Chem 272:12714–12722
Fujihara Y, Murakami M, Inoue N et al (2010) Sperm equatorial segment protein 1, SPESP1, is required for fully fertile sperm in mouse. J Cell Sci 123:1531–1536. doi:10.1242/jcs.067363
Fujihara Y, Satouh Y, Inoue N et al (2012) SPACA1-deficient male mice are infertile with abnormally shaped sperm heads reminiscent of globozoospermia. Development 139:3583–3589. doi:10.1242/dev.081778
Furlong LI, Harris JD, Vazquez-Levin MH (2005) Binding of recombinant human proacrosin/acrosin to zona pellucida (ZP) glycoproteins. I. Studies with recombinant human ZPA, ZPB, and ZPC. Fertil Steril 83:1780–1790. doi:10.1016/j.fertnstert.2004.12.042
Guyonnet B, Egge N, Cornwall GA (2014) Functional amyloids in the mouse sperm acrosome. Mol Cell Biol 34:2624–2634. doi:10.1128/MCB.00073-14
Gyamera-Acheampong C, Tantibhedhyangkul J, Weerachatyanukul W et al (2006) Sperm from mice genetically deficient for the PCSK4 proteinase exhibit accelerated capacitation, precocious acrosome reaction, reduced binding to egg zona pellucida, and impaired fertilizing ability. Biol Reprod 74:666–673. doi:10.1095/biolreprod.105.046821
Hao J, Chen M, Ji S et al (2014) Equatorin is not essential for acrosome biogenesis but is required for the acrosome reaction. Biochem Biophys Res Commun 444:537–542. doi:10.1016/j.bbrc.2014.01.080
Hardy DM, Garbers DL (1995) A sperm membrane protein that binds in a species-specific manner to the egg extracellular matrix is homologous to von Willebrand factor. J Biol Chem 270:26025–26028. doi:10.1074/jbc.270.44.26025
He S, Lin Y-L, Liu Y-X (1999) Functionally inactive protein C inhibitor in seminal plasma may be associated with infertility. Mol Hum Reprod 5:513–519. doi:10.1093/molehr/5.6.513
He J, Xia M, Tsang WH et al (2015) ICA1L forms BAR-domain complexes with PICK1 and is crucial for acrosome formation in spermiogenesis. J Cell Sci 128:3822–3836. doi:10.1242/jcs.173534
Hermans JM, Jones R, Stone SR (1994) Rapid inhibition of the sperm protease acrosin by protein C inhibitor. Biochemistry (Mosc) 33:5440–5444. doi:10.1021/bi00184a012
Hirohashi N, Gerton GL, Buffone MG (2011) Video imaging of the sperm acrosome reaction during in vitro fertilization. Commun Integr Biol 4:471–476. doi:10.4161/cib.4.4.15636
Holstein AF, Roosen-Runge EC (1981) Atlas of human spermatogenesis. Grosse, Berlin
Honda A, Yamagata K, Sugiura S et al (2002) A mouse serine protease TESP5 is selectively included into lipid rafts of sperm membrane presumably as a glycosylphosphatidylinositol-anchored protein. J Biol Chem 277:16976–16984
Howes E, Pascall JC, Engel W, Jones R (2001) Interactions between mouse ZP2 glycoprotein and proacrosin; a mechanism for secondary binding of sperm to the zona pellucida during fertilization. J Cell Sci 114:4127–4136
Inoue N, Ikawa M, Nakanishi T et al (2003) Disruption of mouse CD46 causes an accelerated spontaneous acrosome reaction in sperm. Mol Cell Biol 23:2614–2622. doi:10.1128/MCB.23.7.2614-2622.2003
Jin M, Fujiwara E, Kakiuchi Y et al (2011) Most fertilizing mouse spermatozoa begin their acrosome reaction before contact with the zona pellucida during in vitro fertilization. Proc Natl Acad Sci 108:4892–4896. doi:10.1073/pnas.1018202108
Kanemori Y, Ryu J-H, Sudo M et al (2013) Two functional forms of ACRBP/sp32 are produced by pre-mRNA alternative splicing in the mouse. Biol Reprod 88:105. doi:10.1095/biolreprod.112.107425
Kang-Decker N, Mantchev GT, Juneja SC et al (2001) Lack of acrosome formation in Hrb-deficient mice. Science 294:1531–1533. doi:10.1126/science.1063665
Kawano N, Kang W, Yamashita M et al (2010) Mice lacking two sperm serine proteases, ACR and PRSS21, are subfertile, but the mutant sperm are infertile in vitro. Biol Reprod 83:359–369. doi:10.1095/biolreprod.109.083089
Kierszenbaum AL, Tres LL, Rivkin E et al (2004) The acroplaxome is the docking site of Golgi-derived myosin Va/Rab27a/b-containing proacrosomal vesicles in wild-type and Hrb mutant mouse spermatids. Biol Reprod 70:1400–1410. doi:10.1095/biolreprod.103.025346
Kim KS, Cha MC, Gerton GL (2001) Mouse sperm protein sp56 is a component of the acrosomal matrix. Biol Reprod 64:36–43
Kim K-S, Foster JA, Kvasnicka KW, Gerton GL (2011) Transitional states of acrosomal exocytosis and proteolytic processing of the acrosomal matrix in guinea pig sperm. Mol Reprod Dev 78:930–941. doi:10.1002/mrd.21387
Kimura T, Ito C, Watanabe S et al (2003) Mouse germ cell-less as an essential component for nuclear integrity. Mol Cell Biol 23:1304–1315. doi:10.1128/MCB.23.4.1304-1315.2003
Kimura M, Kim E, Kang W et al (2009) Functional roles of mouse sperm hyaluronidases, HYAL5 and SPAM1, in fertilization. Biol Reprod 81:939–947. doi:10.1095/biolreprod.109.078816
Liegel RP, Handley MT, Ronchetti A et al (2013) Loss-of-function mutations in TBC1D20 cause cataracts and male infertility in blind-sterile mice and Warburg micro syndrome in humans. Am J Hum Genet 93:1001–1014. doi:10.1016/j.ajhg.2013.10.011
Lin Y-N, Roy A, Yan W et al (2007) Loss of zona pellucida binding proteins in the acrosomal matrix disrupts acrosome biogenesis and sperm morphogenesis. Mol Cell Biol 27:6794–6805. doi:10.1128/MCB.01029-07
Litscher ES, Wassarman PM (2014) Evolution, structure, and synthesis of vertebrate egg-coat proteins. Trends Dev Biol 8:65–76
Manandhar G, Toshimori K (2001) Exposure of sperm head equatorin after acrosome reaction and its fate after fertilization in mice. Biol Reprod 65:1425–1436. doi:10.1095/biolreprod65.5.1425
Mbikay M, Tadros H, Ishida N et al (1997) Impaired fertility in mice deficient for the testicular germ-cell protease PC4. Proc Natl Acad Sci 94:6842–6846
Miyazaki T, Mori M, Yoshida CA et al (2012) Galnt3 deficiency disrupts acrosome formation and leads to oligoasthenoteratozoospermia. Histochem Cell Biol 139:339–354. doi:10.1007/s00418-012-1031-3
Moore A, Penfold LM, Johnson JL et al (1993) Human sperm–egg binding is inhibited by peptides corresponding to core region of an acrosomal serine protease inhibitor. Mol Reprod Dev 34:280–291. doi:10.1002/mrd.1080340308
Mori E, Baba T, Iwamatsu A, Mori T (1993) Purification and characterization of a 38-kDa protein, sp38, with zona pellucida-binding property from porcine epididymal sperm. Biochem Biophys Res Commun 196:196–202. doi:10.1006/bbrc.1993.2234
Muro Y, Buffone MG, Okabe M, Gerton GL (2012) Function of the acrosomal matrix: zona pellucida 3 receptor (ZP3R/sp56) is not essential for mouse fertilization. Biol Reprod 86:1–6. doi:10.1095/biolreprod.111.095877
Nayernia K, Vauti F, Meinhardt A et al (2003) Inactivation of a testis-specific Lis1 transcript in mice prevents spermatid differentiation and causes male infertility. J Biol Chem 278:48377–48385. doi:10.1074/jbc.M309583200
Netzel-Arnett S, Bugge TH, Hess RA et al (2009) The glycosylphosphatidylinositol-anchored serine protease PRSS21 (testisin) imparts murine epididymal sperm cell maturation and fertilizing ability. Biol Reprod 81:921–932. doi:10.1095/biolreprod.109.076273
Noland TD, Friday BB, Maulit MT, Gerton GL (1994) The sperm acrosomal matrix contains a novel member of the pentaxin family of calcium-dependent binding proteins. J Biol Chem 269:32607–32614
Pierre V, Martinez G, Coutton C et al (2012) Absence of Dpy19l2, a new inner nuclear membrane protein, causes globozoospermia in mice by preventing the anchoring of the acrosome to the nucleus. Development 139:2955–2965. doi:10.1242/dev.077982
Reid MS, Blobel CP (1994) Apexin, an acrosomal pentaxin. J Biol Chem 269:32615–32620
Salustri A, Garlanda C, Hirsch E et al (2004) PTX3 plays a key role in the organization of the cumulus oophorus extracellular matrix and in vivo fertilization. Development 131:1577–1586. doi:10.1242/dev.01056
Sato H, Taketomi Y, Isogai Y et al (2010) Group III secreted phospholipase A2 regulates epididymal sperm maturation and fertility in mice. J Clin Invest 120:1400–1414. doi:10.1172/JCI40493
Setiadi D, Lin M, Rodger JC (1997) Posttesticular development of spermatozoa of the tammar wallaby (Macropus eugenii). J Anat 190:275–288. doi:10.1046/j.1469-7580.1997.19020275.x
Shetty J, Wolkowicz MJ, Digilio LC et al (2003) SAMP14, a novel, acrosomal membrane-associated, glycosylphosphatidylinositol-anchored member of the Ly-6/urokinase-type plasminogen activator receptor superfamily with a role in sperm-egg Interaction. J Biol Chem 278:30506–30515. doi:10.1074/jbc.M301713200
Sotomayor RE, Handel MA (1986) Failure of acrosome assembly in a male sterile mouse mutant. Biol Reprod 34:171–182. doi:10.1095/biolreprod34.1.171
Tardif S, Wilson MD, Wagner R et al (2010) Zonadhesin is essential for species specificity of sperm adhesion to the egg’s zona pellucida. J Biol Chem 285(32):24863–24870. doi:10.1074/jbc.M110.123125
Tardif S, Guyonnet B, Cormier N, Cornwall GA (2012) Alteration in the processing of the ACRBP/sp32 protein and sperm head/acrosome malformations in proprotein convertase 4 (PCSK4) null mice. Mol Hum Reprod 18:298–307. doi:10.1093/molehr/gas009
Uhrin P, Dewerchin M, Hilpert M et al (2000) Disruption of the protein C inhibitor gene results in impaired spermatogenesis and male infertility. J Clin Invest 106:1531–1539. doi:10.1172/JCI10768
Uhrin P, Schöfer C, Zaujec J et al (2007) Male fertility and protein C inhibitor/plasminogen activator inhibitor-3 (PCI): localization of PCI in mouse testis and failure of single plasminogen activator knockout to restore spermatogenesis in PCI-deficient mice. Fertil Steril 88:1049–1057. doi:10.1016/j.fertnstert.2006.11.193
Varani S, Elvin JA, Yan C et al (2002) Knockout of pentraxin 3, a downstream target of growth differentiation factor-9, causes female subfertility. Mol Endocrinol 16:1154–1167. doi:10.1210/me.16.6.1154
Wassarman PM, Jovine L, Litscher ES et al (2004) Egg–sperm interactions at fertilization in mammals. Eur J Obstet Gynecol Reprod Biol 115(Suppl 1):S57–S60. doi:10.1016/j.ejogrb.2004.01.025
Westbrook-Case VA, Winfrey VP, Olson GE (1994) A domain-specific 50-kilodalton structural protein of the acrosomal matrix is processed and released during the acrosome reaction in the guinea pig. Biol Reprod 51:1–13. doi:10.1095/biolreprod51.1.1
Wolkowicz MJ, Shetty J, Westbrook A et al (2003) Equatorial segment protein defines a discrete acrosomal subcompartment persisting throughout acrosomal biogenesis. Biol Reprod 69:735–745. doi:10.1095/biolreprod.103.016675
Xiao N, Kam C, Shen C et al (2009) PICK1 deficiency causes male infertility in mice by disrupting acrosome formation. J Clin Invest 119:802–812. doi:10.1172/JCI36230
Xu X, Toselli PA, Russell LD, Seldin DC (1999) Globozoospermia in mice lacking the casein kinase II α′ catalytic subunit. Nat Genet 23:118–121. doi:10.1038/12729
Yamagata K, Murayama K, Okabe M et al (1998) Acrosin accelerates the dispersal of sperm acrosomal proteins during acrosome reaction. J Biol Chem 273:10470–10474. doi:10.1074/jbc.273.17.10470
Yao R, Ito C, Natsume Y et al (2002) Lack of acrosome formation in mice lacking a Golgi protein, GOPC. Proc Natl Acad Sci 99:11211–11216. doi:10.1073/pnas.162027899
Yu Y, Xu W, Yi Y-J et al (2006) The extracellular protein coat of the inner acrosomal membrane is involved in zona pellucida binding and penetration during fertilization: characterization of its most prominent polypeptide (IAM38). Dev Biol 290:32–43. doi:10.1016/j.ydbio.2005.11.003
Zheng X, Geiger M, Ecke S et al (1994) Inhibition of acrosin by protein C inhibitor and localization of protein C inhibitor to spermatozoa. Am J Physiol 267:C466–C472
Zhou C, Kang W, Baba T (2012) Functional characterization of double-knockout mouse sperm lacking SPAM1 and ACR or SPAM1 and PRSS21 in fertilization. J Reprod Dev 58:330–337. doi:10.1262/jrd.2011-006
Acknowledgments
This work was supported in part by grants R21-ES024527 and P30-ES013508 from the National Institute of Environmental Health Sciences to GLG, and Chenery and Rashkind Research Grants from Randolph-Macon College to JAF.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Foster, J.A., Gerton, G.L. (2016). The Acrosomal Matrix. In: Buffone, M. (eds) Sperm Acrosome Biogenesis and Function During Fertilization. Advances in Anatomy, Embryology and Cell Biology, vol 220. Springer, Cham. https://doi.org/10.1007/978-3-319-30567-7_2
Download citation
DOI: https://doi.org/10.1007/978-3-319-30567-7_2
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-30565-3
Online ISBN: 978-3-319-30567-7
eBook Packages: MedicineMedicine (R0)