{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T19:43:11Z","timestamp":1790883791447,"version":"4.1.0"},"reference-count":47,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,10,21]],"date-time":"2020-10-21T00:00:00Z","timestamp":1603238400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,10,21]],"date-time":"2020-10-21T00:00:00Z","timestamp":1603238400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100008732","name":"Uehara Memorial Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008732","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Promotion and Science (JSPS) KAKENHI Grant-in-Aid for Scientific Research","award":["18K06948"],"award-info":[{"award-number":["18K06948"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>PRDX4, a member of peroxiredoxin family, is largely concentrated in the endoplasmic reticulum (ER) and plays a pivotal role in the redox relay during oxidative protein folding as well as in peroxidase reactions. A testis-specific PRDX4 variant transcript (PRDX4t) lacks the conventional exon 1, which encodes the signal peptide that is required for entry into the ER lumen, but instead carries alternative exon 1, which is transcribed from the upstream promoter in a testis-specific manner and results in the PRDX4t protein being localized in the cytosol. However, the potential roles of PRDX4t in male genital action remain unknown. Using a CRISPR\/Cas9 system, we first disrupted the testis-specific promoter\/exon 1 and generated mice that were specifically deficient in PRDX4t. The resulting PRDX4t knockout (KO) mice underwent normal spermatogenesis and showed no overt abnormalities in the testis. Mating PRDX4t KO male mice with wild-type (WT) female mice produced normal numbers of offspring, indicating that a PRDX4t deficiency alone had no effect on fertility in the male mice. We then generated mice lacking both PRDX4 and PRDX4t by disrupting exon 2, which is communal to these variants. The resulting double knockout (DKO) mice were again fertile, and mature sperm isolated from the epididymis of DKO mice exhibited a normal fertilizing ability in vitro. In the meantime, the protein levels of glutathione peroxidase 4 (GPX4), which plays an essential role in the disulfide bond formation during spermatogenesis, were significantly increased in the testis and caput epididymis of the DKO mice compared with the WT mice. Based on these results, we conclude that the disruption of the function of PRDX4t in the spermatogenic process appears to be compensated by other factors including GPX4.<\/jats:p>","DOI":"10.1038\/s41598-020-74667-9","type":"journal-article","created":{"date-parts":[[2020,10,21]],"date-time":"2020-10-21T10:04:15Z","timestamp":1603274655000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Testis-specific peroxiredoxin 4 variant is not absolutely required for spermatogenesis and fertility in mice"],"prefix":"10.1038","volume":"10","author":[{"given":"Takujiro","family":"Homma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiro","family":"Kurahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Ishii","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuyuki","family":"Shirasawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junichi","family":"Fujii","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,10,21]]},"reference":[{"key":"74667_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.14348\/molcells.2016.2368","volume":"39","author":"SG Rhee","year":"2016","unstructured":"Rhee, S. G. Overview on peroxiredoxin. Mol. Cells 39, 1\u20135 (2016).","journal-title":"Mol. Cells"},{"key":"74667_CR2","doi-asserted-by":"publisher","first-page":"4403","DOI":"10.1074\/jbc.R111.283432","volume":"287","author":"SG Rhee","year":"2012","unstructured":"Rhee, S. G., Woo, H. A., Kil, I. S. & Bae, S. H. Peroxiredoxin functions as a peroxidase and a regulator and sensor of local peroxides. J. Biol. Chem. 287, 4403\u20134410 (2012).","journal-title":"J. Biol. Chem."},{"key":"74667_CR3","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1016\/S0014-5793(98)01736-0","volume":"443","author":"A Matsumoto","year":"1999","unstructured":"Matsumoto, A. et al. Cloning of the peroxiredoxin gene family in rats and characterization of the fourth member. FEBS Lett. 443, 246\u2013250 (1999).","journal-title":"FEBS Lett."},{"key":"74667_CR4","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1042\/BJ20071428","volume":"411","author":"TJ Tavender","year":"2008","unstructured":"Tavender, T. J., Sheppard, A. M. & Bulleid, N. J. Peroxiredoxin IV is an endoplasmic reticulum-localized enzyme forming oligomeric complexes in human cells. Biochem. J. 411, 191\u2013199 (2008).","journal-title":"Biochem. J."},{"key":"74667_CR5","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1146\/annurev-biochem-062209-093836","volume":"80","author":"I Braakman","year":"2011","unstructured":"Braakman, I. & Bulleid, N. J. Protein folding and modification in the mammalian endoplasmic reticulum. Annu. Rev. Biochem. 80, 71\u201399 (2011).","journal-title":"Annu. Rev. Biochem."},{"key":"74667_CR6","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1016\/j.molcel.2010.11.010","volume":"40","author":"E Zito","year":"2010","unstructured":"Zito, E. et al. Oxidative protein folding by an endoplasmic reticulum-localized peroxiredoxin. Mol. Cell 40, 787\u2013797 (2010).","journal-title":"Mol. Cell"},{"key":"74667_CR7","doi-asserted-by":"publisher","first-page":"2456","DOI":"10.1038\/srep02456","volume":"3","author":"Y Sato","year":"2013","unstructured":"Sato, Y. et al. Synergistic cooperation of PDI family members in peroxiredoxin 4-driven oxidative protein folding. Sci. Rep. 3, 2456 (2013).","journal-title":"Sci. Rep."},{"key":"74667_CR8","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.molcel.2012.08.010","volume":"48","author":"E Zito","year":"2012","unstructured":"Zito, E., Hansen, H. G., Yeo, G. S. H., Fujii, J. & Ron, D. Endoplasmic reticulum thiol oxidase deficiency leads to ascorbic acid depletion and noncanonical scurvy in mice. Mol. Cell 48, 39\u201351 (2012).","journal-title":"Mol. Cell"},{"key":"74667_CR9","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1016\/j.freeradbiomed.2015.01.025","volume":"83","author":"J Fujii","year":"2015","unstructured":"Fujii, J., Ikeda, Y., Kurahashi, T. & Homma, T. Physiological and pathological views of peroxiredoxin 4. Free Radic. Biol. Med. 83, 373\u2013379 (2015).","journal-title":"Free Radic. Biol. Med."},{"key":"74667_CR10","doi-asserted-by":"publisher","first-page":"2812904","DOI":"10.1155\/2018\/2812904","volume":"2018","author":"T Homma","year":"2018","unstructured":"Homma, T. et al. Double knockout of peroxiredoxin 4 (Prdx4) and superoxide dismutase 1 (Sod1) in mice results in severe liver failure. Oxid. Med. Cell. Longev. 2018, 2812904 (2018).","journal-title":"Oxid. Med. Cell. Longev."},{"key":"74667_CR11","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1093\/oxfordjournals.jbchem.a022632","volume":"127","author":"A Okado-Matsumoto","year":"2000","unstructured":"Okado-Matsumoto, A., Matsumoto, A., Fujii, J. & Taniguchi, N. Peroxiredoxin IV is a secretable protein with heparin-binding properties under reduced conditions. J. Biochem. 127, 493\u2013501 (2000).","journal-title":"J. Biochem."},{"key":"74667_CR12","doi-asserted-by":"publisher","first-page":"3053","DOI":"10.1046\/j.1432-1327.2001.02200.x","volume":"268","author":"I Sasagawa","year":"2001","unstructured":"Sasagawa, I. et al. Possible involvement of the membrane-bound form of peroxiredoxin 4 in acrosome formation during spermiogenesis of rats. Eur. J. Biochem. 268, 3053\u20133061 (2001).","journal-title":"Eur. J. Biochem."},{"key":"74667_CR13","doi-asserted-by":"publisher","first-page":"39002","DOI":"10.1074\/jbc.M111.257220","volume":"286","author":"SH Yim","year":"2011","unstructured":"Yim, S. H. et al. Identification and characterization of alternatively transcribed form of peroxiredoxin IV gene that is specifically expressed in spermatids of postpubertal mouse testis. J. Biol. Chem. 286, 39002\u201339012 (2011).","journal-title":"J. Biol. Chem."},{"key":"74667_CR14","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1042\/BJ20081526","volume":"419","author":"Y Iuchi","year":"2009","unstructured":"Iuchi, Y. et al. Peroxiredoxin 4 knockout results in elevated spermatogenic cell death via oxidative stress. Biochem. J. 419, 149\u2013158 (2009).","journal-title":"Biochem. J."},{"key":"74667_CR15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.pep.2010.02.001","volume":"72","author":"Y Ikeda","year":"2010","unstructured":"Ikeda, Y., Ito, R., Ihara, H., Okada, T. & Fujii, J. Expression of N-terminally truncated forms of rat peroxiredoxin-4 in insect cells. Protein Expr. Purif. 72, 1\u20137 (2010).","journal-title":"Protein Expr. Purif."},{"key":"74667_CR16","doi-asserted-by":"publisher","first-page":"156","DOI":"10.3164\/jcbn.16-96","volume":"60","author":"E Tasaki","year":"2017","unstructured":"Tasaki, E. et al. Protective role of testis-specific peroxiredoxin 4 against cellular oxidative stress. J. Clin. Biochem. Nutr. 60, 156\u2013161 (2017).","journal-title":"J. Clin. Biochem. Nutr."},{"key":"74667_CR17","doi-asserted-by":"publisher","first-page":"e24376","DOI":"10.4161\/spmg.24376","volume":"3","author":"RL Kanippayoor","year":"2013","unstructured":"Kanippayoor, R. L., Alpern, J. H. M. & Moehring, A. J. Protamines and spermatogenesis in Drosophila and Homo sapiens: A comparative analysis. Spermatogenesis 3, e24376 (2013).","journal-title":"Spermatogenesis"},{"key":"74667_CR18","first-page":"82","volume":"28","author":"C Cho","year":"2001","unstructured":"Cho, C. et al. Haploinsufficiency of protamine-1 or -2 causes infertility in mice. Nat. Genet. 28, 82\u201386 (2001).","journal-title":"Nat. Genet."},{"key":"74667_CR19","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1095\/biolreprod.102.015115","volume":"69","author":"C Cho","year":"2003","unstructured":"Cho, C. et al. Protamine 2 deficiency leads to sperm DNA damage and embryo death in mice. Biol. Reprod. 69, 211\u2013217 (2003).","journal-title":"Biol. Reprod."},{"key":"74667_CR20","doi-asserted-by":"publisher","first-page":"e979108","DOI":"10.4161\/21565562.2014.979108","volume":"4","author":"J Fujii","year":"2014","unstructured":"Fujii, J. & Imai, H. Redox reactions in mammalian spermatogenesis and the potential targets of reactive oxygen species under oxidative stress. Spermatogenesis 4, e979108 (2014).","journal-title":"Spermatogenesis"},{"key":"74667_CR21","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1080\/01926230290105721","volume":"30","author":"JR Latendresse","year":"2002","unstructured":"Latendresse, J. R., Warbrittion, A. R., Jonassen, H. & Creasy, D. M. Fixation of testes and eyes using a modified Davidson\u2019s fluid: Comparison with Bouin\u2019s fluid and conventional Davidson\u2019s fluid. Toxicol. Pathol. 30, 524\u2013533 (2002).","journal-title":"Toxicol. Pathol."},{"key":"74667_CR22","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.abb.2016.06.004","volume":"604","author":"T Kurahashi","year":"2016","unstructured":"Kurahashi, T. et al. Ascorbic acid prevents acetaminophen-induced hepatotoxicity in mice by ameliorating glutathione recovery and autophagy. Arch. Biochem. Biophys. 604, 36\u201346 (2016).","journal-title":"Arch. Biochem. Biophys."},{"key":"74667_CR23","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1080\/10715760500130517","volume":"39","author":"T Ishii","year":"2005","unstructured":"Ishii, T. et al. Accelerated impairment of spermatogenic cells in SOD1-knockout mice under heat stress. Free Radic. Res. 39, 697\u2013705 (2005).","journal-title":"Free Radic. Res."},{"key":"74667_CR24","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1042\/BJ20061386","volume":"402","author":"Y Iuchi","year":"2007","unstructured":"Iuchi, Y. et al. Elevated oxidative stress in erythrocytes due to a SOD1 deficiency causes anaemia and triggers autoantibody production. Biochem. J. 402, 219\u2013227 (2007).","journal-title":"Biochem. J."},{"key":"74667_CR25","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1093\/molehr\/gaq007","volume":"16","author":"N Kimura","year":"2010","unstructured":"Kimura, N. et al. Intrinsic oxidative stress causes either 2-cell arrest or cell death depending on developmental stage of the embryos from SOD1-deficient mice. Mol. Hum. Reprod. 16, 441\u2013451 (2010).","journal-title":"Mol. Hum. Reprod."},{"key":"74667_CR26","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1016\/j.yexcr.2016.10.006","volume":"349","author":"T Homma","year":"2016","unstructured":"Homma, T. & Fujii, J. Heat stress promotes the down-regulation of IRE1\u03b1 in cells: An atypical modulation of the UPR pathway. Exp. Cell Res. 349, 128\u2013138 (2016).","journal-title":"Exp. Cell Res."},{"key":"74667_CR27","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1016\/j.bbrc.2013.04.032","volume":"434","author":"J-H Kim","year":"2013","unstructured":"Kim, J.-H. et al. Testicular hyperthermia induces unfolded protein response signaling activation in spermatocyte. Biochem. Biophys. Res. Commun. 434, 861\u2013866 (2013).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"74667_CR28","doi-asserted-by":"publisher","first-page":"7637","DOI":"10.1128\/MCB.25.17.7637-7644.2005","volume":"25","author":"M Conrad","year":"2005","unstructured":"Conrad, M. et al. The nuclear form of phospholipid hydroperoxide glutathione peroxidase is a protein thiol peroxidase contributing to sperm chromatin stability. Mol. Cell. Biol. 25, 7637\u20137644 (2005).","journal-title":"Mol. Cell. Biol."},{"key":"74667_CR29","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1095\/biolreprod.115.137646","volume":"94","author":"B Ozkosem","year":"2016","unstructured":"Ozkosem, B., Feinstein, S. I., Fisher, A. B. & O\u2019Flaherty, C. Absence of peroxiredoxin 6 amplifies the effect of oxidant stress on mobility and SCSA\/CMA3 defined chromatin quality and impairs fertilizing ability of mouse spermatozoa. Biol. Reprod. 94, 68 (2016).","journal-title":"Biol. Reprod."},{"key":"74667_CR30","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.redox.2015.02.004","volume":"5","author":"B Ozkosem","year":"2015","unstructured":"Ozkosem, B., Feinstein, S. I., Fisher, A. B. & O\u2019Flaherty, C. Advancing age increases sperm chromatin damage and impairs fertility in peroxiredoxin 6 null mice. Redox Biol. 5, 15\u201323 (2015).","journal-title":"Redox Biol."},{"key":"74667_CR31","doi-asserted-by":"crossref","unstructured":"O\u2019Flaherty, C. Peroxiredoxin 6: The protector of male fertility. Antioxidants (Basel, Switzerland)7 (2018).","DOI":"10.3390\/antiox7120173"},{"key":"74667_CR32","doi-asserted-by":"crossref","unstructured":"Wu, P. Y., Scarlata, E. & O\u2019Flaherty, C. Long-term adverse effects of oxidative stress on rat epididymis and spermatozoa. Antioxidants (Basel, Switzerland)9 (2020).","DOI":"10.3390\/antiox9020170"},{"key":"74667_CR33","doi-asserted-by":"crossref","first-page":"73","DOI":"10.4103\/1008-682X.170863","volume":"19","author":"Y Liu","year":"2017","unstructured":"Liu, Y. & O\u2019Flaherty, C. In vivo oxidative stress alters thiol redox status of peroxiredoxin 1 and 6 and impairs rat sperm quality. Asian J. Androl. 19, 73\u201379 (2017).","journal-title":"Asian J. Androl."},{"key":"74667_CR34","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1111\/andr.12630","volume":"7","author":"C O\u2019Flaherty","year":"2019","unstructured":"O\u2019Flaherty, C. Orchestrating the antioxidant defenses in the epididymis. Andrology 7, 662\u2013668 (2019).","journal-title":"Andrology"},{"key":"74667_CR35","doi-asserted-by":"publisher","first-page":"12201","DOI":"10.1073\/pnas.1635054100","volume":"100","author":"N Schultz","year":"2003","unstructured":"Schultz, N., Hamra, F. K. & Garbers, D. L. 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. 100, 12201\u201312206 (2003).","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"74667_CR36","doi-asserted-by":"publisher","first-page":"7704","DOI":"10.1073\/pnas.1608458113","volume":"113","author":"H Miyata","year":"2016","unstructured":"Miyata, H. et al. Genome engineering uncovers 54 evolutionarily conserved and testis-enriched genes that are not required for male fertility in mice. Proc. Natl. Acad. Sci. U. S. A. 113, 7704\u20137710 (2016).","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"74667_CR37","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1093\/biolre\/ioz103","volume":"101","author":"Y Lu","year":"2019","unstructured":"Lu, Y. et al. CRISPR\/Cas9-mediated genome editing reveals 30 testis-enriched genes dispensable for male fertility in mice\u2020. Biol. Reprod. 101, 501\u2013511 (2019).","journal-title":"Biol. Reprod."},{"key":"74667_CR38","first-page":"84","volume":"102","author":"RJ Holcomb","year":"2020","unstructured":"Holcomb, R. J. et al. The testis-specific serine proteases PRSS44, PRSS46, and PRSS54 are dispensable for male mouse fertility. Biol. Reprod. 102, 84\u201391 (2020).","journal-title":"Biol. Reprod."},{"key":"74667_CR39","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-017-17765-5","volume":"8","author":"M Khan","year":"2018","unstructured":"Khan, M. et al. The evolutionarily conserved genes: Tex37, Ccdc73, Prss55 and Nxt2 are dispensable for fertility in mice. Sci. Rep. 8, 1\u20138 (2018).","journal-title":"Sci. Rep."},{"key":"74667_CR40","doi-asserted-by":"publisher","first-page":"e38565","DOI":"10.1371\/journal.pone.0038565","volume":"7","author":"A Noblanc","year":"2012","unstructured":"Noblanc, A. et al. Epididymis response partly compensates for spermatozoa oxidative defects in snGPx4 and GPx5 double mutant mice. PLoS ONE 7, e38565 (2012).","journal-title":"PLoS ONE"},{"key":"74667_CR41","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1016\/S0006-291X(03)00734-4","volume":"305","author":"H Imai","year":"2003","unstructured":"Imai, H. et al. Early embryonic lethality caused by targeted disruption of the mouse PHGPx gene. Biochem. Biophys. Res. Commun. 305, 278\u2013286 (2003).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"74667_CR42","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3164\/jcbn.09-94R","volume":"46","author":"H Imai","year":"2010","unstructured":"Imai, H. New strategy of functional analysis of PHGPx knockout mice model using transgenic rescue method and Cre-LoxP system. J. Clin. Biochem. Nutr. 46, 1\u201313 (2010).","journal-title":"J. Clin. Biochem. Nutr."},{"key":"74667_CR43","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1016\/S0891-5849(02)01360-6","volume":"34","author":"LJ Yant","year":"2003","unstructured":"Yant, L. J. et al. The selenoprotein GPX4 is essential for mouse development and protects from radiation and oxidative damage insults. Free Radic. Biol. Med. 34, 496\u2013502 (2003).","journal-title":"Free Radic. Biol. Med."},{"key":"74667_CR44","doi-asserted-by":"publisher","first-page":"3233","DOI":"10.1096\/fj.09-132795","volume":"23","author":"M Schneider","year":"2009","unstructured":"Schneider, M. et al. Mitochondrial glutathione peroxidase 4 disruption causes male infertility. FASEB J. 23, 3233\u20133242 (2009).","journal-title":"FASEB J."},{"key":"74667_CR45","doi-asserted-by":"publisher","first-page":"32522","DOI":"10.1074\/jbc.M109.016139","volume":"284","author":"H Imai","year":"2009","unstructured":"Imai, H. et al. Depletion of selenoprotein GPx4 in spermatocytes causes male infertility in mice. J. Biol. Chem. 284, 32522\u201332532 (2009).","journal-title":"J. Biol. Chem."},{"key":"74667_CR46","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1095\/biolreprod64.2.674","volume":"64","author":"H Imai","year":"2001","unstructured":"Imai, H. et al. Failure of the expression of phospholipid hydroperoxide glutathione peroxidase in the spermatozoa of human infertile males. Biol. Reprod. 64, 674\u2013683 (2001).","journal-title":"Biol. Reprod."},{"key":"74667_CR47","doi-asserted-by":"publisher","first-page":"1236","DOI":"10.1096\/fj.00-0655fje","volume":"15","author":"H Pfeifer","year":"2001","unstructured":"Pfeifer, H. et al. Identification of a specific sperm nuclei selenoenzyme necessary for protamine thiol cross-linking during sperm maturation. FASEB J. 15, 1236\u20131238 (2001).","journal-title":"FASEB J."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-74667-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-74667-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-74667-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,10]],"date-time":"2023-10-10T07:40:14Z","timestamp":1696923614000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-74667-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,21]]},"references-count":47,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["74667"],"URL":"https:\/\/doi.org\/10.1038\/s41598-020-74667-9","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,21]]},"assertion":[{"value":"6 April 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 September 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 October 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"17934"}}