Clinical and Experimental Reproductive Medicine

The Korean Society for Reproductive Medicine (대한생식의학회)
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Ovastacin: An oolemma protein that cleaves the zona pellucida to prevent polyspermy

  • Inyoung Kang (Department of Biomedical Laboratory Sciences, Eulji University) ;
  • Myoungjoo Koo (Department of Biomedical Laboratory Sciences, Eulji University) ;
  • Hyejin Yoon (Department of Senior Healthcare, Graduate School of Eulji University) ;
  • Beom Seok Park (Department of Biomedical Laboratory Sciences, Eulji University) ;
  • Jin Hyun Jun (Department of Biomedical Laboratory Sciences, Eulji University) ;
  • Jaewang Lee (Department of Biomedical Laboratory Sciences, Eulji University)
  • Received : 2023.03.29
  • Accepted : 2023.05.02
  • Published : 2023.09.30
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Abstract

Monospermy occurs in the process of normal fertilization where a single sperm fuses with the egg, resulting in the formation of a diploid zygote. During the process of fertilization, the sperm must penetrate the zona pellucida (ZP), the outer layer of the egg, to reach the egg's plasma membrane. Once a sperm binds to the ZP, it undergoes an acrosomal reaction, which involves the release of enzymes from the sperm's acrosome that help it to penetrate the ZP. Ovastacin is one of the enzymes that is involved in breaking down the ZP. Studies have shown that ovastacin is necessary for the breakdown of the ZP and for successful fertilization to occur. However, the activity of ovastacin is tightly regulated to ensure that only one sperm can fertilize the egg. One way in which ovastacin helps to prevent polyspermy (the fertilization of an egg by more than one sperm) is by rapidly degrading the ZP after a sperm has penetrated it. This makes it difficult for additional sperm to penetrate the ZP and fertilize the egg. Ovastacin is also thought to play a role in the block to polyspermy, a mechanism that prevents additional sperm from fusing with the egg's plasma membrane after fertilization has occurred. In summary, the role of ovastacin in monospermic fertilization is to help ensure that only one sperm can fertilize the egg, while preventing polyspermy and ensuring successful fertilization.

Keywords

Acknowledgement

This study was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education, Science, and Technology (2018R1D1A1B07046419 and 2020R1F1A1071918).

References

  1. Harrison D, Buskmiller C, Chireau M, Ruppersberger LA, Yeung PP Jr. Systematic review of ovarian activity and potential for embryo formation and loss during the use of hormonal contraception. Linacre Q 2018;85:453-69. https://doi.org/10.1177/0024363918815611
  2. Teal S, Edelman A. Contraception selection, effectiveness, and adverse effects: a review. JAMA 2021;326:2507-18. https://doi.org/10.1001/jama.2021.21392
  3. Casado-Espada NM, de Alarcon R, de la Iglesia-Larrad JI, Bote-Bonaechea B, Montejo AL. Hormonal contraceptives, female sexual dysfunction, and managing strategies: a review. J Clin Med 2019;8:908.
  4. Kent K, Johnston M, Strump N, Garcia TX. Toward development of the male pill: a decade of potential non-hormonal contraceptive targets. Front Cell Dev Biol 2020;8:61.
  5. Naz RK. Vaccine for human contraception targeting sperm Izumo protein and YLP12 dodecamer peptide. Protein Sci 2014;23:857-68. https://doi.org/10.1002/pro.2476
  6. Liu M. The biology and dynamics of mammalian cortical granules. Reprod Biol Endocrinol 2011;9:149.
  7. Korschgen H, Jager C, Tan K, Buchholz M, Stocker W, Ramsbeck D. A primary evaluation of potential small-molecule inhibitors of the astacin metalloproteinase ovastacin, a novel drug target in female infertility treatment. ChemMedChem 2020;15:1499-504. https://doi.org/10.1002/cmdc.202000397
  8. Duncan FE, Que EL, Zhang N, Feinberg EC, O'Halloran TV, Woodruff TK. The zinc spark is an inorganic signature of human egg activation. Sci Rep 2016;6:24737.
  9. Tokuhiro K, Dean J. Glycan-independent gamete recognition triggers egg zinc sparks and ZP2 cleavage to prevent polyspermy. Dev Cell 2018;46:627-40. https://doi.org/10.1016/j.devcel.2018.07.020
  10. Korschgen H, Kuske M, Karmilin K, Yiallouros I, Balbach M, Floehr J, et al. Intracellular activation of ovastacin mediates pre-fertilization hardening of the zona pellucida. Mol Hum Reprod 2017;23:607-16. https://doi.org/10.1093/molehr/gax040
  11. Pires ES, Hlavin C, Macnamara E, Ishola-Gbenla K, Doerwaldt C, Chamberlain C, et al. SAS1B protein [ovastacin] shows temporal and spatial restriction to oocytes in several eutherian orders and initiates translation at the primary to secondary follicle transition. Dev Dyn 2013;242:1405-26. https://doi.org/10.1002/dvdy.24040
  12. Sachdev M, Mandal A, Mulders S, Digilio LC, Panneerdoss S, Suryavathi V, et al. Oocyte specific oolemmal SAS1B involved in sperm binding through intra-acrosomal SLLP1 during fertilization. Dev Biol 2012;363:40-51. https://doi.org/10.1016/j.ydbio.2011.12.021
  13. Xiong B, Zhao Y, Beall S, Sadusky AB, Dean J. A unique egg cortical granule localization motif is required for ovastacin sequestration to prevent premature ZP2 cleavage and ensure female fertility in mice. PLoS Genet 2017;13:e1006580.
  14. Burkart AD, Xiong B, Baibakov B, Jimenez-Movilla M, Dean J. Ovastacin, a cortical granule protease, cleaves ZP2 in the zona pellucida to prevent polyspermy. J Cell Biol 2012;197:37-44. https://doi.org/10.1083/jcb.201112094
  15. Que EL, Duncan FE, Bayer AR, Philips SJ, Roth EW, Bleher R, et al. Zinc sparks induce physiochemical changes in the egg zona pellucida that prevent polyspermy. Integr Biol (Camb) 2017;9:135-44. https://doi.org/10.1039/C6IB00212A
  16. Avella MA, Xiong B, Dean J. The molecular basis of gamete recognition in mice and humans. Mol Hum Reprod 2013;19:279-89. https://doi.org/10.1093/molehr/gat004
  17. Vogt EJ, Tokuhiro K, Guo M, Dale R, Yang G, Shin SW, et al. Anchoring cortical granules in the cortex ensures trafficking to the plasma membrane for post-fertilization exocytosis. Nat Commun 2019;10:2271.
  18. de Figueiredo JR, de Lima LF, Silva JR, Santos RR. Control of growth and development of preantral follicle: insights from in vitro culture. Anim Reprod 2018;15(Suppl 1):648-59. https://doi.org/10.21451/1984-3143-AR2018-0019
  19. Dietzel E, Floehr J, Van de Leur E, Weiskirchen R, Jahnen-Dechent W. Recombinant fetuin-B protein maintains high fertilization rate in cumulus cell-free mouse oocytes. Mol Hum Reprod 2017;23:25-33. https://doi.org/10.1093/molehr/gaw067
  20. Ducibella T, Kurasawa S, Rangarajan S, Kopf GS, Schultz RM. Precocious loss of cortical granules during mouse oocyte meiotic maturation and correlation with an egg-induced modification of the zona pellucida. Dev Biol 1990;137:46-55. https://doi.org/10.1016/0012-1606(90)90006-5
  21. Schiewe MC, Araujo E Jr, Asch RH, Balmaceda JP. Enzymatic characterization of zona pellucida hardening in human eggs and embryos. J Assist Reprod Genet 1995;12:2-7. https://doi.org/10.1007/BF02214120
  22. Maddirevula S, Coskun S, Al-Qahtani M, Aboyousef O, Alhassan S, Aldeery M, et al. ASTL is mutated in female infertility. Hum Genet 2022;141:49-54. https://doi.org/10.1007/s00439-021-02388-8
  23. Wassarman PM, Litscher ES. Zona pellucida genes and proteins: essential players in mammalian oogenesis and fertility. Genes (Basel) 2021;12:1266.
  24. Wassarman PM, Litscher ES. Female fertility and the zona pellucida. Elife 2022;11:e76106.
  25. Wang J, Yang X, Sun X, Ma L, Yin Y, He G, et al. A novel homozygous nonsense mutation in zona pellucida 1 (ZP1) causes human female empty follicle syndrome. J Assist Reprod Genet 2021;38:1459-68. https://doi.org/10.1007/s10815-021-02136-x
  26. Cao Q, Zhao C, Zhang X, Zhang H, Lu Q, Wang C, et al. Heterozygous mutations in ZP1 and ZP3 cause formation disorder of ZP and female infertility in human. J Cell Mol Med 2020;24:8557-66. https://doi.org/10.1111/jcmm.15482
  27. Zhou Z, Ni C, Wu L, Chen B, Xu Y, Zhang Z, et al. Novel mutations in ZP1, ZP2, and ZP3 cause female infertility due to abnormal zona pellucida formation. Hum Genet 2019;138:327-37. https://doi.org/10.1007/s00439-019-01990-1
  28. Denecke B, Graber S, Schafer C, Heiss A, Woltje M, Jahnen-Dechent W. Tissue distribution and activity testing suggest a similar but not identical function of fetuin-B and fetuin-A. Biochem J 2003;376(Pt 1):135-45. https://doi.org/10.1042/bj20030676
  29. Fang L, Hu X, Cui L, Lv P, Ma X, Ye Y. Serum and follicular fluid fetuin-B levels are correlated with fertilization rates in conventional IVF cycles. J Assist Reprod Genet 2019;36:1101-7. https://doi.org/10.1007/s10815-019-01454-5
  30. Dietzel E, Wessling J, Floehr J, Schafer C, Ensslen S, Denecke B, et al. Fetuin-B, a liver-derived plasma protein is essential for fertilization. Dev Cell 2013;25:106-12. https://doi.org/10.1016/j.devcel.2013.03.001
  31. Karmilin K, Schmitz C, Kuske M, Korschgen H, Olf M, Meyer K, et al. Mammalian plasma fetuin-B is a selective inhibitor of ovastacin and meprin metalloproteinases. Sci Rep 2019;9:546.
  32. Chekol Abebe E, Tilahun Muche Z, Behaile T/Mariam A, Mengie Ayele T, Mekonnen Agidew M, Teshome Azezew M, et al. The structure, biosynthesis, and biological roles of fetuin-A: a review. Front Cell Dev Biol 2022;10:945287.
  33. Bourebaba L, Marycz K. Pathophysiological implication of fetuin-A glycoprotein in the development of metabolic disorders: a concise review. J Clin Med 2019;8:2033.
  34. Shim YS, Kang MJ, Oh YJ, Baek JW, Yang S, Hwang IT. Fetuin-A as an alternative marker for insulin resistance and cardiovascular risk in prepubertal children. J Atheroscler Thromb 2017;24:1031-8. https://doi.org/10.5551/jat.38323
  35. Pan X, Wen SW, Bestman PL, Kaminga AC, Acheampong K, Liu A. Fetuin-A in metabolic syndrome: a systematic review and meta-analysis. PLoS One 2020;15:e0229776.
  36. Cuppari A, Korschgen H, Fahrenkamp D, Schmitz C, Guevara T, Karmilin K, et al. Structure of mammalian plasma fetuin-B and its mechanism of selective metallopeptidase inhibition. IUCrJ 2019;6(Pt 2):317-30. https://doi.org/10.1107/S2052252519001568
  37. Stocker W, Karmilin K, Hildebrand A, Westphal H, Yiallouros I, Weiskirchen R, et al. Mammalian gamete fusion depends on the inhibition of ovastacin by fetuin-B. Biol Chem 2014;395:1195-9. https://doi.org/10.1515/hsz-2014-0189