Hostname: page-component-5b777bbd6c-gtgcz Total loading time: 0 Render date: 2025-06-18T22:30:08.925Z Has data issue: false hasContentIssue false
  • English
  • Français

The role of sperm protein in mammal fertilization: insights into gamete adhesion, membrane fusion and oocyte activation

Published online by Cambridge University Press:  13 May 2025

Kaiyue Hu Open the ORCID record for Kaiyue Hu [Opens in a new window] ,
Bo Dong ,
Yugang Wang  and
Xiangrui Meng
Kaiyue Hu*
Affiliation:
Department of Reproductive Medicine, Luoyang maternal and child health hospital, Luoyang, 471000, China Luoyang branch of the National Center for assisted reproduction and eugenics, Luoyang, China Key Laboratory of reproduction and genetics, Luoyang, China Institute of Reproductive Medicine, Luoyang, China
Bo Dong
Affiliation:
Department of Reproductive Medicine, Luoyang maternal and child health hospital, Luoyang, 471000, China Luoyang branch of the National Center for assisted reproduction and eugenics, Luoyang, China Key Laboratory of reproduction and genetics, Luoyang, China Institute of Andrology, Luoyang, China
Yugang Wang
Affiliation:
Department of Reproductive Medicine, Luoyang maternal and child health hospital, Luoyang, 471000, China Luoyang branch of the National Center for assisted reproduction and eugenics, Luoyang, China Key Laboratory of reproduction and genetics, Luoyang, China Institute of Andrology, Luoyang, China
Xiangrui Meng*
Affiliation:
The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
*
Corresponding authors: Xiangrui Meng; Email: 2201224155@qq.com, Kaiyue Hu; Email: 345233314@qq.com
Corresponding authors: Xiangrui Meng; Email: 2201224155@qq.com, Kaiyue Hu; Email: 345233314@qq.com
Get access Rights & Permissions [Opens in a new window]

Abstract

Globally, numerous infertile couples have been assisted by extensive research on mammalian fertilization and the rapid development of Assisted Reproductive Technology (ART). However, 5%–15% of the couples that are selected for in vitro fertilization (IVF) experience a total fertilization failure (TFF), where no zygotes develop despite oocytes and semen parameters appear to be normal. Notably, an essential early event in fertilization is the binding of spermatozoa to the oocyte’s external envelope, which followed by the spermatozoa-oocyte fusion. Meanwhile, oocyte activation is a crucial cellular process necessary to block polyspermy and start the development of the zygote. Improper membrane fusion of gametes has been demonstrated to be one of the mechanisms of TFF. Moreover, considering the large amount of research on sperm proteins in recent years, thus in this review, we characterize the role and molecular mechanisms of sperm proteins in the three key processes of gamete adhesion and fusion and oocyte activation, which would provide a comprehensive understanding of the role of sperm proteins in fertilization in mammals and a favourable reference for future studies in assisted reproduction due to FF.

Keywords

Fertilizationgametereproductionspermatozoa-oocyte interactionsperm protein
Type
Review Article
Information
Zygote , Volume 33 , Issue 2 , April 2025 , pp. 63 - 73
Check for updates
Copyright
© The Author(s), 2025. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Article purchase

Temporarily unavailable

References

Aarabi, M., Balakier, H., Bashar, S., Moskovtsev, S. I., Sutovsky, P., Librach, C. L., & Oko, R. (2014) Sperm-derived WW domain-binding protein, PAWP, elicits calcium oscillations and oocyte activation in humans and mice. The FASEB Journal 28(10), 4434–4440. doi: 10.1096/fj.14-256495 CrossRefGoogle ScholarPubMed
Almeida, E. A., Huovila, A. P., Sutherland, A. E., Stephens, L. E., Calarco, P. G., Shaw, L. M., … White, J. M. (1995) Mouse egg integrin alpha 6 beta 1 functions as a sperm receptor. Cell 81(7), 1095–1104. doi: 10.1016/s0092-8674(05)80014-5 CrossRefGoogle ScholarPubMed
Amdani, S. N., Yeste, M., Jones, C., & Coward, K. (2015) Sperm factors and oocyte activation: current controversies and considerations. Biology of Reproduction 93(2), 50. doi: 10.1095/biolreprod.115.130609 CrossRefGoogle Scholar
An, G., Huang, T. H., Wang, D. G., Xie, Q. D., Ma, L., & Chen, D. Y. (2009) In vitro and in vivo studies evaluating recombinant plasmid pCXN2-mIzumo as a potential immunocontraceptive antigen. American Journal of Reproductive Immunology 61(3), 227–235. doi: 10.1111/j.1600-0897.2009.00685.x CrossRefGoogle ScholarPubMed
Aydin, H., Sultana, A., Li, S., Thavalingam, A., & Lee, J. E. (2016) Molecular architecture of the human sperm IZUMO1 and egg JUNO fertilization complex. Nature 534(7608), 562–565. doi: 10.1038/nature18595 CrossRefGoogle ScholarPubMed
Backs, J., Stein, P., Backs, T., Duncan, F. E., Grueter, C. E., McAnally, J., … Olson, E. N. (2010) The gamma isoform of CaM kinase II controls mouse egg activation by regulating cell cycle resumption. Proceedings of the National Academy of Sciences of the United States of America 107(1), 81–86. doi: 10.1073/pnas.0912658106 CrossRefGoogle ScholarPubMed
Barbaux, S., Ialy-Radio, C., Chalbi, M., Dybal, E., Homps-Legrand, M., Do Cruzeiro, M., … Ziyyat, A. (2020) Sperm SPACA6 protein is required for mammalian Sperm-Egg adhesion/fusion. Scientific Reports 10(1), 5335. doi: 10.1038/s41598-020-62091-y CrossRefGoogle ScholarPubMed
Bardhi, E., & Drakopoulos, P. (2021) Update on male Infertility. Journal of Clinical Medicine 10(20), 4771. doi: 10.3390/jcm10204771 CrossRefGoogle ScholarPubMed
Baskaran, S., Agarwal, A., Leisegang, K., Pushparaj, P. N., Panner Selvam, M. K., & Henkel, R. (2021) An in-depth bibliometric analysis and current perspective on male infertility research. The World Journal of Men’s Health 39(2), 302–314. doi: 10.5534/wjmh.180114 CrossRefGoogle ScholarPubMed
Bianchi, E., Doe, B., Goulding, D., & Wright, G. J. (2014) Juno is the egg Izumo receptor and is essential for mammalian fertilization. Nature 508(7497), 483–487. doi: 10.1038/nature13203 CrossRefGoogle Scholar
Bianchi, E., & Wright, G. J. (2020) Find and fuse: unsolved mysteries in sperm-egg recognition. PLoS Biology 18(11), e3000953. doi: 10.1371/journal.pbio.3000953 CrossRefGoogle ScholarPubMed
Binner, M. I., Kogan, A., Panser, K., Schleiffer, A., Deneke, V. E., & Pauli, A. (2021) The sperm protein Spaca6 is essential for fertilization in zebrafish. Frontiers in Cell and Developmental Biology 9, 806982. doi: 10.3389/fcell.2021.806982 CrossRefGoogle ScholarPubMed
Bjerregaard, B., Lemmen, J. G., Petersen, M. R., Ostrup, E., Iversen, L. H., Almstrup, K., … Ziebe, S. (2014) Syncytin-1 and its receptor is present in human gametes. Journal of Assisted Reproduction and Genetics 31(5), 533–539. doi: 10.1007/s10815-014-0224-1 CrossRefGoogle ScholarPubMed
Black, R. A., & White, J. M. (1998) ADAMs: focus on the protease domain. Current Opinion in Cell Biology 10(5), 654–659. doi: 10.1016/s0955-0674(98)80042-2 CrossRefGoogle ScholarPubMed
Bonte, D., Ferrer-Buitrago, M., Dhaenens, L., Popovic, M., Thys, V., De Croo, I., … Heindryckx, B. (2019) Assisted oocyte activation significantly increases fertilization and pregnancy outcome in patients with low and total failed fertilization after intracytoplasmic sperm injection: a 17-year retrospective study. Fertility and Sterility 112(2), 266–274. doi: 10.1016/j.fertnstert.2019.04.006 CrossRefGoogle ScholarPubMed
Bouftas, N., Schneider, L., Halder, M., Demmig, R., Baack, M., Cladière, D., … Mayer, T. U. (2022) Cyclin B3 implements timely vertebrate oocyte arrest for fertilization. Developmental Cell 57(19), 2305–2320.e6. doi: 10.1016/j.devcel.2022.09.005 CrossRefGoogle ScholarPubMed
Bronson, R. A., Fusi, F. M., Calzi, F., Doldi, N., & Ferrari, A. (1999) Evidence that a functional fertilin-like ADAM plays a role in human sperm-oolemmal interactions. Molecular Human Reproduction 5(5), 433–440. doi: 10.1093/molehr/5.5.433 CrossRefGoogle Scholar
Brukman, N. G., Li, X., & Podbilewicz, B. (2021) Fusexins, HAP2/GCS1 and evolution of gamete fusion. Frontiers in Cell and Developmental Biology 9, 824024. doi: 10.3389/fcell.2021.824024 CrossRefGoogle ScholarPubMed
Brukman, N. G., Nakajima, K. P., Valansi, C., Flyak, K., Li, X., Higashiyama, T., & Podbilewicz, B. (2023) A novel function for the sperm adhesion protein IZUMO1 in cell-cell fusion. The Journal of Cell Biology 222(2). doi: 10.1083/jcb.202207147 CrossRefGoogle ScholarPubMed
Carvacho, I., Piesche, M., Maier, T. J., & Machaca, K. (2018) Ion channel function during oocyte maturation and fertilization. Frontiers in Cell and Developmental Biology 6, 63. doi: 10.3389/fcell.2018.00063 CrossRefGoogle ScholarPubMed
Chalbi, M., Barraud-Lange, V., Ravaux, B., Howan, K., Rodriguez, N., Soule, P., … Gourier, C. (2014) Binding of sperm protein Izumo1 and its egg receptor Juno drives Cd9 accumulation in the intercellular contact area prior to fusion during mammalian fertilization. Development (Cambridge, England) 141(19), 3732–3739. doi: 10.1242/dev.111534 CrossRefGoogle ScholarPubMed
Cheung, S., Xie, P., Parrella, A., Keating, D., Rosenwaks, Z., & Palermo, G. D. (2020) Identification and treatment of men with phospholipase Czeta-defective spermatozoa. Fertility and Sterility 114(3), 535–544. doi: 10.1016/j.fertnstert.2020.04.044 CrossRefGoogle ScholarPubMed
Cho, C., Bunch, D. O., Faure, J. E., Goulding, E. H., Eddy, E. M., Primakoff, P., & Myles, D. G. (1998) Fertilization defects in sperm from mice lacking fertilin beta. Science 281(5384), 1857–1859. doi: 10.1126/science.281.5384.1857 CrossRefGoogle ScholarPubMed
D’Cruz, O. J. (1996) Adhesion molecules in human sperm-oocyte interaction: relevance to infertility. Frontiers in Bioscience 1, d161–176. doi: 10.2741/a123 CrossRefGoogle Scholar
Dai, J., Zhang, T., Guo, J., Zhou, Q., Gu, Y., Zhang, J., … Lin, G. (2021) Homozygous pathogenic variants in ACTL9 cause fertilization failure and male infertility in humans and mice. American Journal of Human Genetics 108(3), 469–481. doi: 10.1016/j.ajhg.2021.02.004 CrossRefGoogle ScholarPubMed
Daldello, E. M., Luong, X. G., Yang, C.-R., Kuhn, J., & Conti, M. (2019) Cyclin B2 is required for progression through meiosis in mouse oocytes. Development (Cambridge, England) 146(8), dev172734. doi: 10.1242/dev.172734 CrossRefGoogle ScholarPubMed
Diaz-Gimeno, P., & Meseguer, M. (2019) Noninvasive embryo assessment: how close are we? Fertility and Sterility 112(5), 811–812. doi: 10.1016/j.fertnstert.2019.09.005 CrossRefGoogle ScholarPubMed
Duncan, F. E., Schindler, K., Schultz, R. M., Blengini, C. S., Stein, P., Stricker, S. A., … Williams, C. J. (2020) Unscrambling the oocyte and the egg: clarifying terminology of the female gamete in mammals. Molecular Human Reproduction 26(11), 797–800. doi: 10.1093/molehr/gaaa066 CrossRefGoogle ScholarPubMed
Edwards, D. R., Handsley, M. M., & Pennington, C. J. (2008) The ADAM metalloproteinases. Molecular Aspects of Medicine 29(5), 258–289. doi: 10.1016/j.mam.2008.08.001 CrossRefGoogle ScholarPubMed
Enoiu, S. I., Nygaard, M. B., Bungum, M., Ziebe, S., Petersen, M. R., & Almstrup, K. (2022) Expression of membrane fusion proteins in spermatozoa and total fertilisation failure during in vitro fertilisation. Andrology 10(7), 1317–1327. doi: 10.1111/andr.13215 CrossRefGoogle ScholarPubMed
Evans, J. P. (2012) Sperm-egg interaction. Annual Review of Physiology 74, 477–502. doi: 10.1146/annurev-physiol-020911-153339 CrossRefGoogle ScholarPubMed
Fenichel, P., & Durand-Clement, M. (1998) Role of integrins during fertilization in mammals. Human Reproduction 13(Suppl 4), 31–46. doi: 10.1093/humrep/13.suppl_4.31 CrossRefGoogle ScholarPubMed
Fujihara, Y., Lu, Y., Noda, T., Oji, A., Larasati, T., Kojima-Kita, K., … Ikawa, M. (2020) Spermatozoa lacking Fertilization Influencing Membrane Protein (FIMP) fail to fuse with oocytes in mice. Proceedings of the National Academy of Sciences of the United States of America 117(17), 9393–9400. doi: 10.1073/pnas.1917060117 CrossRefGoogle ScholarPubMed
Garner, T. B., Hester, J. M., Carothers, A., & Diaz, F. J. (2021) Role of zinc in female reproduction. Biology of Reproduction 104(5), 976–994. doi: 10.1093/biolre/ioab023 CrossRefGoogle ScholarPubMed
Gemberling, M. P., Siklenka, K., Rodriguez, E., Tonn-Eisinger, K. R., Barrera, A., Liu, F., … Gersbach, C. A. (2021) Transgenic mice for in vivo epigenome editing with CRISPR-based systems. Nature Methods 18(8), 965–974. doi: 10.1038/s41592-021-01207-2 CrossRefGoogle ScholarPubMed
Grayson, P. (2015) Izumo1 and Juno: the evolutionary origins and coevolution of essential sperm-egg binding partners. Royal Society Open Science 2(12), 150296. doi: 10.1098/rsos.150296 CrossRefGoogle ScholarPubMed
Hachem, A., Godwin, J., Ruas, M., Lee, H. C., Ferrer Buitrago, M., Ardestani, G., … Parrington, J. (2017) PLCzeta is the physiological trigger of the Ca(2+) oscillations that induce embryogenesis in mammals but conception can occur in its absence. Development (Cambridge, England) 144(16), 2914–2924. doi: 10.1242/dev.150227 CrossRefGoogle Scholar
Hamilton, L. E., Suzuki, J., Acteau, G., Shi, M., Xu, W., Meinsohn, M. C., … Oko, R. (2018) WBP2 shares a common location in mouse spermatozoa with WBP2NL/PAWP and like its descendent is a candidate mouse oocyte-activating factor. Biology of Reproduction 99(6), 1171–1183. doi: 10.1093/biolre/ioy156 Google ScholarPubMed
Han, C., Choi, E., Park, I., Lee, B., Jin, S., Kim, D. H., … Cho, C. (2009) Comprehensive analysis of reproductive ADAMs: relationship of ADAM4 and ADAM6 with an ADAM complex required for fertilization in mice. Biology of Reproduction 80(5), 1001–1008. doi: 10.1095/biolreprod.108.073700 CrossRefGoogle Scholar
Heim, A., Tischer, T., & Mayer, T. U. (2018) Calcineurin promotes APC/C activation at meiotic exit by acting on both XErp1 and Cdc20. EMBO Reports 19(12), e46433. doi: 10.15252/embr.201846433 CrossRefGoogle ScholarPubMed
Hirohashi, N., & Yanagimachi, R. (2018) Sperm acrosome reaction: its site and role in fertilization. Biology of Reproduction 99(1), 127–133. doi: 10.1093/biolre/ioy045 CrossRefGoogle ScholarPubMed
Hooft van Huijsduijnen, R. (1998) ADAM 20 and 21; two novel human testis-specific membrane metalloproteases with similarity to fertilin-alpha. Gene 206(2), 273–282. doi: 10.1016/s0378-1119(97)00597-0 CrossRefGoogle ScholarPubMed
Hu, Q., Duncan, F. E., Nowakowski, A. B., Antipova, O. A., Woodruff, T. K., O’Halloran, T. V., & Wolfner, M. F. (2020) Zinc dynamics during drosophila oocyte maturation and egg activation. iScience 23(7), 101275. doi: 10.1016/j.isci.2020.101275 CrossRefGoogle ScholarPubMed
Inoue, N., Hagihara, Y., & Wada, I. (2021) Evolutionarily conserved sperm factors, DCST1 and DCST2, are required for gamete fusion. Elife 10, e66313. doi: 10.7554/eLife.66313 CrossRefGoogle ScholarPubMed
Inoue, N., Hagihara, Y., Wright, D., Suzuki, T., & Wada, I. (2015) Oocyte-triggered dimerization of sperm IZUMO1 promotes sperm-egg fusion in mice. Nature Communications 6, 8858. doi: 10.1038/ncomms9858 CrossRefGoogle ScholarPubMed
Inoue, N., Hamada, D., Kamikubo, H., Hirata, K., Kataoka, M., Yamamoto, M., … Hagihara, Y. (2013) Molecular dissection of IZUMO1, a sperm protein essential for sperm-egg fusion. Development (Cambridge, England) 140(15), 3221–3229. doi: 10.1242/dev.094854 CrossRefGoogle ScholarPubMed
Inoue, N., Ikawa, M., Isotani, A., & Okabe, M. (2005) The immunoglobulin superfamily protein Izumo is required for sperm to fuse with eggs. Nature 434(7030), 234–238. doi: 10.1038/nature03362 CrossRefGoogle ScholarPubMed
Inoue, N., & Wada, I. (2022) Deletion of the initial methionine codon of the Tmem95 gene causes subfertility, but not complete infertility, in male mice. Biology of Reproduction 106(3), 378–381. doi: 10.1093/biolre/ioab246 CrossRefGoogle Scholar
Kaji, K., Oda, S., Shikano, T., Ohnuki, T., Uematsu, Y., Sakagami, J., … Kudo, A. (2000) The gamete fusion process is defective in eggs of Cd9-deficient mice. Nature Genetics 24(3), 279–282. doi: 10.1038/73502 CrossRefGoogle ScholarPubMed
Kashir, J., Ganesh, D., Jones, C., & Coward, K. (2022) Oocyte activation deficiency and assisted oocyte activation: mechanisms, obstacles and prospects for clinical application. Human Reproduction Open 2022(2), hoac003. doi: 10.1093/hropen/hoac003 CrossRefGoogle ScholarPubMed
Kim, A. M., Bernhardt, M. L., Kong, B. Y., Ahn, R. W., Vogt, S., Woodruff, T. K., & O’Halloran, T. V. (2011) Zinc sparks are triggered by fertilization and facilitate cell cycle resumption in mammalian eggs. ACS Chemical Biology 6(7), 716–723. doi: 10.1021/cb200084y CrossRefGoogle ScholarPubMed
Kim, E., Nishimura, H., & Baba, T. (2003) Differential localization of ADAM1a and ADAM1b in the endoplasmic reticulum of testicular germ cells and on the surface of epididymal sperm. Biochemical and Biophysical Research Communications 304(2), 313–319. doi: 10.1016/s0006-291x(03)00588-6 CrossRefGoogle ScholarPubMed
Kim, T., Oh, J., Woo, J. M., Choi, E., Im, S. H., Yoo, Y. J., … Cho, C. (2006) Expression and relationship of male reproductive ADAMs in mouse. Biology of Reproduction 74(4), 744–750. doi: 10.1095/biolreprod.105.048892 CrossRefGoogle Scholar
Kong, B. Y., Bernhardt, M. L., Kim, A. M., O’Halloran, T. V., & Woodruff, T. K. (2012) Zinc maintains prophase I arrest in mouse oocytes through regulation of the MOS-MAPK pathway. Biology of Reproduction 87(1), 11, 11-12. doi: 10.1095/biolreprod.112.099390 CrossRefGoogle ScholarPubMed
Krauchunas, A. R., Marcello, M. R., & Singson, A. (2016) The molecular complexity of fertilization: Introducing the concept of a fertilization synapse. Molecular Reproduction and Development 83(5), 376–386. doi: 10.1002/mrd.22634 CrossRefGoogle ScholarPubMed
Krauchunas, A. R., & Wolfner, M. F. (2013) Molecular changes during egg activation. Current Topics in Developmental Biology 102, 267–292. doi: 10.1016/B978-0-12-416024-8.00010-6 CrossRefGoogle ScholarPubMed
Lamas-Toranzo, I., Hamze, J. G., Bianchi, E., Fernandez-Fuertes, B., Perez-Cerezales, S., Laguna-Barraza, R., … Bermejo-Alvarez, P. (2020) TMEM95 is a sperm membrane protein essential for mammalian fertilization. Elife 9, e53913. doi: 10.7554/eLife.53913 CrossRefGoogle ScholarPubMed
Lara-Gonzalez, P., Moyle, M. W., Budrewicz, J., Mendoza-Lopez, J., Oegema, K., & Desai, A. (2019) The G2-to-M transition is ensured by a dual mechanism that protects cyclin B from degradation by Cdc20-activated APC/C. Developmental Cell 51(3), 313–325 e310. doi: 10.1016/j.devcel.2019.09.005 CrossRefGoogle ScholarPubMed
Le Naour, F., Rubinstein, E., Jasmin, C., Prenant, M., & Boucheix, C. (2000) Severely reduced female fertility in CD9-deficient mice. Science 287(5451), 319–321. doi: 10.1126/science.287.5451.319 CrossRefGoogle ScholarPubMed
Levasseur, M. D., Thomas, C., Davies, O. R., Higgins, J. M. G., & Madgwick, S. (2019) Aneuploidy in oocytes is prevented by sustained CDK1 activity through degron masking in cyclin B1. Developmental Cell 48(5), 672–684 e675. doi: 10.1016/j.devcel.2019.01.008 CrossRefGoogle ScholarPubMed
Liang, S. C., Moskalenko, M., Van Roey, M., & Jooss, K. (2013) Depletion of regulatory T cells by targeting folate receptor 4 enhances the potency of a GM-CSF-secreting tumor cell immunotherapy. Clinical Immunology 148(2), 287–298. doi: 10.1016/j.clim.2013.05.011 CrossRefGoogle ScholarPubMed
Limatola, N., Chun, J. T., & Santella, L. (2022) Regulation of the actin cytoskeleton-Linked Ca(2+) signaling by intracellular pH in fertilized eggs of sea urchin. Cells 11(9), 1496. doi: 10.3390/cells11091496 CrossRefGoogle ScholarPubMed
Lin, S., Ke, M., Zhang, Y., Yan, Z., & Wu, J. (2021) Structure of a mammalian sperm cation channel complex. Nature 595(7869), 746–750. doi: 10.1038/s41586-021-03742-6 CrossRefGoogle ScholarPubMed
Liu, L., Li, H., Labbe, B., Wang, Y., Mao, S., Cao, Y., … Deng, X. (2019) Involvement of CaMKII in regulating the release of diplotene-arrested mouse oocytes by pAkt1 (Ser473). Cell Cycle 18(21), 2986–2997. doi: 10.1080/15384101.2019.1666596 CrossRefGoogle ScholarPubMed
Lorenzetti, D., Poirier, C., Zhao, M., Overbeek, P. A., Harrison, W., & Bishop, C. E. (2014) A transgenic insertion on mouse chromosome 17 inactivates a novel immunoglobulin superfamily gene potentially involved in sperm-egg fusion. Mammalian Genome 25(3-4), 141–148. doi: 10.1007/s00335-013-9491-x CrossRefGoogle ScholarPubMed
Maniates, K. A., & Singson, A. (2023) Where are all the egg genes? Frontiers in Cell and Developmental Biology 11, 1107312. doi: 10.3389/fcell.2023.1107312 CrossRefGoogle ScholarPubMed
Marangos, P., FitzHarris, G., & Carroll, J. (2003) Ca2+ oscillations at fertilization in mammals are regulated by the formation of pronuclei. Development (Cambridge, England) 130(7), 1461–1472. doi: 10.1242/dev.00340 CrossRefGoogle ScholarPubMed
Mehregan, A., Ardestani, G., Akizawa, H., Carvacho, I., & Fissore, R. (2021) Deletion of TRPV3 and CaV3.2 T-type channels in mice undermines fertility and Ca2+ homeostasis in oocytes and eggs. Journal of Cell Science 134(13), jcs257956. doi: 10.1242/jcs.257956 CrossRefGoogle ScholarPubMed
Merc, V., Frolikova, M., & Komrskova, K. (2021) Role of integrins in sperm activation and fertilization. International Journal of Molecular Sciences 22(21), 11809. doi: 10.3390/ijms222111809 CrossRefGoogle ScholarPubMed
Miyado, K., Yamada, G., Yamada, S., Hasuwa, H., Nakamura, Y., Ryu, F., … Mekada, E. (2000) Requirement of CD9 on the egg plasma membrane for fertilization. Science 287(5451), 321–324. doi: 10.1126/science.287.5451.321 CrossRefGoogle ScholarPubMed
Miyata, H., Castaneda, J. M., Fujihara, Y., Yu, Z., Archambeault, D. R., Isotani, A., … Matzuk, M. M. (2016) Genome engineering uncovers 54 evolutionarily conserved and testis-enriched genes that are not required for male fertility in mice. Proceedings of the National Academy of Sciences of the United States of America 113(28), 7704–7710. doi: 10.1073/pnas.1608458113 CrossRefGoogle Scholar
Naz, R. K. (2009) Status of contraceptive vaccines. American Journal of Reproductive Immunology 61(1), 11–18. doi: 10.1111/j.1600-0897.2008.00663.x CrossRefGoogle ScholarPubMed
Naz, R. K. (2014) Vaccine for human contraception targeting sperm Izumo protein and YLP12 dodecamer peptide. Protein Science : A Publication of the Protein Society 23(7), 857–868. doi: 10.1002/pro.2476 CrossRefGoogle ScholarPubMed
Nishimura, H., Kim, E., Nakanishi, T., & Baba, T. (2004) Possible function of the ADAM1a/ADAM2 Fertilin complex in the appearance of ADAM3 on the sperm surface. The Journal of Biological Chemistry 279(33), 34957–34962. doi: 10.1074/jbc.M314249200 CrossRefGoogle ScholarPubMed
Noda, T., Blaha, A., Fujihara, Y., Gert, K. R., Emori, C., Deneke, V. E., … Ikawa, M. (2022) Sperm membrane proteins DCST1 and DCST2 are required for sperm-egg interaction in mice and fish. Communications Biology 5(1), 332. doi: 10.1038/s42003-022-03289-w CrossRefGoogle ScholarPubMed
Noda, T., Lu, Y., Fujihara, Y., Oura, S., Koyano, T., Kobayashi, S., … Ikawa, M. (2020) Sperm proteins SOF1, TMEM95, and SPACA6 are required for sperm-oocyte fusion in mice. Proceedings of the National Academy of Sciences of the United States of America 117(21), 11493–11502. doi: 10.1073/pnas.1922650117 CrossRefGoogle ScholarPubMed
Nomikos, M., Blayney, L. M., Larman, M. G., Campbell, K., Rossbach, A., Saunders, C. M., … Lai, F. A. (2005) Role of phospholipase C-zeta domains in Ca2+-dependent phosphatidylinositol 4,5-bisphosphate hydrolysis and cytoplasmic Ca2+ oscillations. The Journal of Biological Chemistry 280(35), 31011–31018. doi: 10.1074/jbc.M500629200 CrossRefGoogle ScholarPubMed
Nomikos, M., Elgmati, K., Theodoridou, M., Calver, B. L., Nounesis, G., Swann, K., & Lai, F. A. (2011) Phospholipase Czeta binding to PtdIns(4,5)P2 requires the XY-linker region. Journal of Cell Science 124(Pt 15), 2582–2590. doi: 10.1242/jcs.083485 CrossRefGoogle ScholarPubMed
Nomikos, M., Elgmati, K., Theodoridou, M., Georgilis, A., Gonzalez-Garcia, J. R., Nounesis, G., … Lai, F. A. (2011) Novel regulation of PLCzeta activity via its XY-linker. Biochemical Journal 438(3), 427–432. doi: 10.1042/BJ20110953 CrossRefGoogle ScholarPubMed
Nomikos, M., Kashir, J., Swann, K., & Lai, F. A. (2013) Sperm PLCzeta: from structure to Ca2+ oscillations, egg activation and therapeutic potential. FEBS Letters 587(22), 3609–3616. doi: 10.1016/j.febslet.2013.10.008 CrossRefGoogle ScholarPubMed
Nomikos, M., Sanders, J. R., Theodoridou, M., Kashir, J., Matthews, E., Nounesis, G., … Swann, K. (2014) Sperm-specific post-acrosomal WW-domain binding protein (PAWP) does not cause Ca2+ release in mouse oocytes. Molecular Human Reproduction 20(10), 938–947. doi: 10.1093/molehr/gau056 CrossRefGoogle Scholar
Oh, J. S., Han, C., & Cho, C. (2009) ADAM7 is associated with epididymosomes and integrated into sperm plasma membrane. Molecules and Cells 28(5), 441–446. doi: 10.1007/s10059-009-0140-x Google ScholarPubMed
Oh, J. S., Susor, A., & Conti, M. (2011) Protein tyrosine kinase Wee1B is essential for metaphase II exit in mouse oocytes. Science 332(6028), 462–465. doi: 10.1126/science.1199211 CrossRefGoogle ScholarPubMed
Pausch, H., Kolle, S., Wurmser, C., Schwarzenbacher, H., Emmerling, R., Jansen, S., … Fries, R. (2014) A nonsense mutation in TMEM95 encoding a nondescript transmembrane protein causes idiopathic male subfertility in cattle. PLoS Genetics 10(1), e1004044. doi: 10.1371/journal.pgen.1004044 CrossRefGoogle ScholarPubMed
Pinello, J. F., & Clark, T. G. (2021) HAP2-Mediated gamete fusion: lessons from the world of unicellular eukaryotes. Frontiers in Cell and Developmental Biology 9, 807313. doi: 10.3389/fcell.2021.807313 CrossRefGoogle ScholarPubMed
Prajapati, P., Kane, S., McBrinn, R. C., Dean, M. S., Martins da Silva, S. J., & Brown, S. G. (2022) Elevated and sustained intracellular calcium signalling is necessary for efficacious induction of the human sperm acrosome reaction. International Journal of Molecular Sciences 23(19). doi: 10.3390/ijms231911253 CrossRefGoogle ScholarPubMed
Primakoff, P., & Myles, D. G. (2007) Cell-cell membrane fusion during mammalian fertilization. FEBS Letters 581(11), 2174–2180. doi: 10.1016/j.febslet.2007.02.021 CrossRefGoogle ScholarPubMed
Que, E. L., Duncan, F. E., Lee, H. C., Hornick, J. E., Vogt, S., Fissore, R. A., … Woodruff, T. K. (2019) Bovine eggs release zinc in response to parthenogenetic and sperm-induced egg activation. Theriogenology 127, 41–48. doi: 10.1016/j.theriogenology.2018.12.031 CrossRefGoogle ScholarPubMed
Ramal-Sanchez, M., Bernabo, N., Tsikis, G., Blache, M. C., Labas, V., Druart, X., … Saint-Dizier, M. (2020) Progesterone induces sperm release from oviductal epithelial cells by modifying sperm proteomics, lipidomics and membrane fluidity. Molecular and Cellular Endocrinology 504, 110723. doi: 10.1016/j.mce.2020.110723 CrossRefGoogle ScholarPubMed
Rizo, J., & Sudhof, T. C. (1998) C2-domains, structure and function of a universal Ca2+-binding domain. The Journal of Biological Chemistry 273(26), 15879–15882. doi: 10.1074/jbc.273.26.15879 CrossRefGoogle ScholarPubMed
Roberts, T. M. (2005) Major sperm protein. Current Biology 15(5), R153. doi: 10.1016/j.cub.2005.02.036 CrossRefGoogle ScholarPubMed
Rocks, N., Paulissen, G., El Hour, M., Quesada, F., Crahay, C., Gueders, M., … Cataldo, D. (2008) Emerging roles of ADAM and ADAMTS metalloproteinases in cancer. Biochimie 90(2), 369–379. doi: 10.1016/j.biochi.2007.08.008 CrossRefGoogle ScholarPubMed
Rojas, J., Hinostroza, F., Vergara, S., Pinto-Borguero, I., Aguilera, F., Fuentes, R., & Carvacho, I. (2021) Knockin’ on egg’s door: maternal control of egg activation that influences cortical granule exocytosis in animal species. Frontiers in Cell and Developmental Biology 9, 704867. doi: 10.3389/fcell.2021.704867 CrossRefGoogle ScholarPubMed
Saito, T., Wada, I., & Inoue, N. (2019) Alternative splicing of the Izumo1 gene ensures triggering gamete fusion in mice. Scientific Reports 9(1), 3151. doi: 10.1038/s41598-019-40130-7 CrossRefGoogle ScholarPubMed
Sako, K., Suzuki, K., Isoda, M., Yoshikai, S., Senoo, C., Nakajo, N., … Sagata, N. (2014) Emi2 mediates meiotic MII arrest by competitively inhibiting the binding of Ube2S to the APC/C. Nature Communications 5, 3667. doi: 10.1038/ncomms4667 CrossRefGoogle Scholar
Sanders, J. R., Ashley, B., Moon, A., Woolley, T. E., & Swann, K. (2018) PLCzeta induced Ca(2+) oscillations in mouse eggs involve a positive feedback cycle of Ca(2+) Induced InsP(3) formation from cytoplasmic PIP(2). Frontiers in Cell and Developmental Biology 6, 36. doi: 10.3389/fcell.2018.00036 CrossRefGoogle Scholar
Satouh, Y., Inoue, N., Ikawa, M., & Okabe, M. (2012) Visualization of the moment of mouse sperm-egg fusion and dynamic localization of IZUMO1. Journal of Cell Science 125(Pt 21), 4985–4990. doi: 10.1242/jcs.100867 Google ScholarPubMed
Satouh, Y., Nozawa, K., & Ikawa, M. (2015) Sperm postacrosomal WW domain-binding protein is not required for mouse egg activation. Biology of Reproduction 93(4), 94. doi: 10.1095/biolreprod.115.131441 CrossRefGoogle Scholar
Satouh, Y. J. R. (2022) SPERM FACTORS AND EGG ACTIVATION: The phenotype of PLCZ1-deficient mice. 164(1), F21–F28. doi: 10.1530/rep-21-0438 CrossRefGoogle Scholar
Saunders, C., Larman, M., Parrington, J., Cox, L., Royse, J., Blayney, L., … Lai, F. J. D. (2002) PLC zeta: a sperm-specific trigger of Ca(2+) oscillations in eggs and embryo development. 129(15), 3533–3544. doi: 10.1242/dev.129.15.3533 Google ScholarPubMed
Seals, D. F., & Courtneidge, S. A. (2003) The ADAMs family of metalloproteases: multidomain proteins with multiple functions. Genes & Development 17(1), 7–30. doi: 10.1101/gad.1039703 CrossRefGoogle ScholarPubMed
Sharif, M., Kerns, K., Sutovsky, P., Bovin, N., & Miller, D. J. (2021) Progesterone induces porcine sperm release from oviduct glycans in a proteasome-dependent manner. Reproduction 161(4), 449–457. doi: 10.1530/REP-20-0474 CrossRefGoogle Scholar
Snell, W. J., & White, J. M. (1996) The molecules of mammalian fertilization. Cell 85(5), 629–637. doi: 10.1016/s0092-8674(00)81230-1 CrossRefGoogle ScholarPubMed
Sosnik, J., Miranda, P. V., Spiridonov, N. A., Yoon, S.-Y., Fissore, R. A., Johnson, G. R., & Visconti, P. E. (2009) Tssk6 is required for Izumo relocalization and gamete fusion in the mouse. Journal of Cell Science 122(15), 2741–2749. doi: 10.1242/jcs.047225 CrossRefGoogle ScholarPubMed
Stein, K. K., Primakoff, P., & Myles, D. (2004) Sperm-egg fusion: events at the plasma membrane. Journal of Cell Science 117(Pt 26), 6269–6274. doi: 10.1242/jcs.01598 CrossRefGoogle ScholarPubMed
Suzuki, T., Yoshida, N., Suzuki, E., Okuda, E., & Perry, A. C. (2010) Full-term mouse development by abolishing Zn2+-dependent metaphase II arrest without Ca2+ release. Development (Cambridge, England) 137(16), 2659–2669. doi: 10.1242/dev.049791 CrossRefGoogle ScholarPubMed
Swann, K., & Lai, F. A. (2016) Egg activation at fertilization by a soluble sperm protein. Physiological Reviews 96(1), 127–149. doi: 10.1152/physrev.00012.2015 CrossRefGoogle ScholarPubMed
Tang, S., Lu, Y., Skinner, W. M., Sanyal, M., Lishko, P. V., Ikawa, M., & Kim, P. S. (2022) Human sperm TMEM95 binds eggs and facilitates membrane fusion. Proceedings of the National Academy of Sciences of the United States of America 119(40), e2207805119. doi: 10.1073/pnas.2207805119 CrossRefGoogle ScholarPubMed
Tang, T. S., Dong, J. B., Huang, X. Y., & Sun, F. Z. (2000) Ca(2+) oscillations induced by a cytosolic sperm protein factor are mediated by a maternal machinery that functions only once in mammalian eggs. Development (Cambridge, England) 127(5), 1141–1150. doi: 10.1242/dev.127.5.1141 CrossRefGoogle ScholarPubMed
Tanihara, F., Nakai, M., Men, N. T., Kato, N., Kaneko, H., Noguchi, J., … Kikuchi, K. (2014) Roles of the zona pellucida and functional exposure of the sperm-egg fusion factor ’IZUMO’ during in vitro fertilization in pigs. Animal Science Journal 85(4), 395–404. doi: 10.1111/asj.12164 CrossRefGoogle ScholarPubMed
Theodoridou, M., Nomikos, M., Parthimos, D., Gonzalez-Garcia, J. R., Elgmati, K., Calver, B. L., … Lai, F. A. (2013) Chimeras of sperm PLCzeta reveal disparate protein domain functions in the generation of intracellular Ca2+ oscillations in mammalian eggs at fertilization. Molecular Human Reproduction 19(12), 852–864. doi: 10.1093/molehr/gat070 CrossRefGoogle ScholarPubMed
Van Blerkom, J., & Zimmermann, S. (2016) Ganglioside-enriched microdomains define an oolemma that is functionally polarized with respect to fertilizability in the mouse. Reprod Biomed Online 33(4), 458–475. doi: 10.1016/j.rbmo.2016.06.029 CrossRefGoogle ScholarPubMed
Vasicek, J., Balazi, A., Svoradova, A., Vozaf, J., Dujickova, L., Makarevich, A. V., … Chrenek, P. (2022) Comprehensive flow-cytometric quality assessment of ram sperm intended for gene banking using standard and novel fertility biomarkers. International Journal of Molecular Sciences 23(11), 5920. doi: 10.3390/ijms23115920 CrossRefGoogle ScholarPubMed
Voronina, V. A., Harris, F. M., Schmahl, J., Galligan, C., Oristian, D., Zamfirova, R., … Macdonald, L. E. (2019) Deletion of Adam6 in Mus musculus leads to male subfertility and deficits in sperm ascent into the oviduct. Biology of Reproduction 100(3), 686–696. doi: 10.1093/biolre/ioy210 CrossRefGoogle ScholarPubMed
Walker, L. S. (2007) Regulatory T cells: folate receptor 4: a new handle on regulation and memory? Immunology & Cell Biology 85(7), 506–507. doi: 10.1038/sj.icb.7100115 CrossRefGoogle ScholarPubMed
Wang, D. G., Huang, T. H., Xie, Q. D., & An, G. (2008) Investigation of recombinant mouse sperm protein izumo as a potential immunocontraceptive antigen. American Journal of Reproductive Immunology 59(3), 225–234. doi: 10.1111/j.1600-0897.2007.00571.x CrossRefGoogle ScholarPubMed
Wang, F., Zhang, J., Kong, S., Li, C., Zhang, Z., He, X., … Zhu, F. (2020) A homozygous nonsense mutation of PLCZ1 cause male infertility with oocyte activation deficiency. Journal of Assisted Reproduction and Genetics 37(4), 821–828. doi: 10.1007/s10815-020-01719-4 CrossRefGoogle ScholarPubMed
White, J. M. (2003) ADAMs: modulators of cell-cell and cell-matrix interactions. Current Opinion in Cell Biology 15(5), 598–606. doi: 10.1016/j.ceb.2003.08.001 CrossRefGoogle ScholarPubMed
Wu, A., Sutovsky, P., Xu, W., van der Spoel, A., Platt, F., & Oko, R. J. D. b. (2007) The postacrosomal assembly of sperm head protein, PAWP, is independent of acrosome formation and dependent on microtubular manchette transport. 312(2), 471–483. doi: 10.1016/j.ydbio.2007.08.051 Google ScholarPubMed
Wu, A. T., Sutovsky, P., Manandhar, G., Xu, W., Katayama, M., Day, B. N., … Oko, R. (2007) PAWP, a sperm-specific WW domain-binding protein, promotes meiotic resumption and pronuclear development during fertilization. The Journal of Biological Chemistry 282(16), 12164–12175. doi: 10.1074/jbc.M609132200 CrossRefGoogle ScholarPubMed
Xin, A., Qu, R., Chen, G., Zhang, L., Chen, J., Tao, C., … Sun, X. J. S. a. (2020) ACTL7ADisruption in causes acrosomal ultrastructural defects in human and mouse sperm as a novel male factor inducing early embryonic arrest. 6(35), eaaz4796. doi: 10.1126/sciadv.aaz4796 Google Scholar
Xu, Z., Yao, G., Niu, W., Fan, H., Ma, X., Shi, S., … Sun, Y. (2021) Calcium ionophore (A23187) rescues the activation of unfertilized oocytes after intracytoplasmic sperm injection and chromosome analysis of blastocyst after activation. Frontiers in Endocrinology 12, 692082. doi: 10.3389/fendo.2021.692082 CrossRefGoogle ScholarPubMed
Xue, F., Wang, L., Liu, Y., Tang, H., Xu, W., & Xu, C. (2016) Vaccination with an epitope peptide of IZUMO1 to induce contraception in female Mice. American Journal of Reproductive Immunology 75(4), 474–485. doi: 10.1111/aji.12485 CrossRefGoogle ScholarPubMed
Yamaguchi, T., Hirota, K., Nagahama, K., Ohkawa, K., Takahashi, T., Nomura, T., & Sakaguchi, S. (2007) Control of immune responses by antigen-specific regulatory T cells expressing the folate receptor. Immunity 27(1), 145–159. doi: 10.1016/j.immuni.2007.04.017 CrossRefGoogle ScholarPubMed
Yan, Z., Fan, Y., Wang, F., Yan, Z., Li, M., Ouyang, J., … Lyu, Q. (2020) Novel mutations in PLCZ1 cause male infertility due to fertilization failure or poor fertilization. Human Reproduction (Oxford, England) 35(2), 472–481. doi: 10.1093/humrep/dez282 CrossRefGoogle ScholarPubMed
Zhang, N., Duncan, F. E., Que, E. L., O’Halloran, T. V., & Woodruff, T. K. (2016) The fertilization-induced zinc spark is a novel biomarker of mouse embryo quality and early development. Scientific Reports 6, 22772. doi: 10.1038/srep22772 CrossRefGoogle ScholarPubMed
Zhang, S., Cai, H., Yang, Q., Shi, T., Pan, C., Lei, C., … Lan, X. (2016) Identification of novel alternative splicing transcript and expression analysis of bovine TMEM95 gene. Gene 575(2 Pt 2), 531–536. doi: 10.1016/j.gene.2015.09.026 CrossRefGoogle ScholarPubMed
Zhu, G. Z., Myles, D. G., & Primakoff, P. (2001) Testase 1 (ADAM 24) a plasma membrane-anchored sperm protease implicated in sperm function during epididymal maturation or fertilization. Journal of Cell Science 114(Pt 9), 1787–1794. doi: 10.1242/jcs.114.9.1787 CrossRefGoogle ScholarPubMed