The human sperm proteome-Toward a panel for male fertility testing.
biomarker
disorder
label-free quantification
male infertility
sperm motility
sperm proteome
Journal
Andrology
ISSN: 2047-2927
Titre abrégé: Andrology
Pays: England
ID NLM: 101585129
Informations de publication
Date de publication:
10 2023
10 2023
Historique:
revised:
06
02
2023
received:
07
10
2022
accepted:
05
03
2023
medline:
25
9
2023
pubmed:
11
3
2023
entrez:
10
3
2023
Statut:
ppublish
Résumé
Although male factor accounts for 40%-50% of unintended childlessness, we are far from fully understanding the detailed causes. Usually, affected men cannot even be provided with a molecular diagnosis. We aimed at a higher resolution of the human sperm proteome for better understanding of the molecular causes of male infertility. We were particularly interested in why reduced sperm count decreases fertility despite many normal-looking spermatozoa and which proteins might be involved. Applying mass spectrometry analysis, we qualitatively and quantitatively examined the proteomic profiles of spermatozoa from 76 men differing in fertility. Infertile men had abnormal semen parameters and were involuntarily childless. Fertile subjects exhibited normozoospermia and had fathered children without medical assistance. We discovered proteins from about 7000 coding genes in the human sperm proteome. These were mainly known for involvements in cellular motility, response to stimuli, adhesion, and reproduction. Numbers of sperm proteins showing at least threefold deviating abundances increased from oligozoospermia (N = 153) and oligoasthenozoospermia (N = 154) to oligoasthenoteratozoospermia (N = 368). Deregulated sperm proteins primarily engaged in flagellar assembly and sperm motility, fertilization, and male gametogenesis. Most of these participated in a larger network of male infertility genes and proteins. We expose 31 sperm proteins displaying deviant abundances under infertility, which already were known before to have fertility relevance, including ACTL9, CCIN, CFAP47, CFAP65, CFAP251 (WDR66), DNAH1, and SPEM1. We propose 18 additional sperm proteins with at least eightfold differential abundance for further testing of their diagnostic potential, such as C2orf16, CYLC1, SPATA31E1, SPATA31D1, SPATA48, EFHB (CFAP21), and FAM161A. Our results shed light on the molecular background of the dysfunctionality of the fewer spermatozoa produced in oligozoospermia and syndromes including it. The male infertility network presented may prove useful in further elucidating the molecular mechanism of male infertility.
Sections du résumé
BACKGROUND
Although male factor accounts for 40%-50% of unintended childlessness, we are far from fully understanding the detailed causes. Usually, affected men cannot even be provided with a molecular diagnosis.
OBJECTIVES
We aimed at a higher resolution of the human sperm proteome for better understanding of the molecular causes of male infertility. We were particularly interested in why reduced sperm count decreases fertility despite many normal-looking spermatozoa and which proteins might be involved.
MATERIAL AND METHODS
Applying mass spectrometry analysis, we qualitatively and quantitatively examined the proteomic profiles of spermatozoa from 76 men differing in fertility. Infertile men had abnormal semen parameters and were involuntarily childless. Fertile subjects exhibited normozoospermia and had fathered children without medical assistance.
RESULTS
We discovered proteins from about 7000 coding genes in the human sperm proteome. These were mainly known for involvements in cellular motility, response to stimuli, adhesion, and reproduction. Numbers of sperm proteins showing at least threefold deviating abundances increased from oligozoospermia (N = 153) and oligoasthenozoospermia (N = 154) to oligoasthenoteratozoospermia (N = 368). Deregulated sperm proteins primarily engaged in flagellar assembly and sperm motility, fertilization, and male gametogenesis. Most of these participated in a larger network of male infertility genes and proteins.
DISCUSSION
We expose 31 sperm proteins displaying deviant abundances under infertility, which already were known before to have fertility relevance, including ACTL9, CCIN, CFAP47, CFAP65, CFAP251 (WDR66), DNAH1, and SPEM1. We propose 18 additional sperm proteins with at least eightfold differential abundance for further testing of their diagnostic potential, such as C2orf16, CYLC1, SPATA31E1, SPATA31D1, SPATA48, EFHB (CFAP21), and FAM161A.
CONCLUSION
Our results shed light on the molecular background of the dysfunctionality of the fewer spermatozoa produced in oligozoospermia and syndromes including it. The male infertility network presented may prove useful in further elucidating the molecular mechanism of male infertility.
Substances chimiques
Proteome
0
WDR66 protein, human
0
Calcium-Binding Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1418-1436Informations de copyright
© 2023 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology.
Références
Vogt PH. Molecular genetics of human male infertility: from genes to new therapeutic perspectives. Curr Pharm Des. 2004;10(5):471-500. doi:10.2174/1381612043453261
Ji G, Long Y, Zhou Y, Huang C, Gu A, Wang X. Common variants in mismatch repair genes associated with increased risk of sperm DNA damage and male infertility. BMC Med. 2012;10:49. doi:10.1186/1741-7015-10-49
Kumar N, Singh AK. Trends of male factor infertility, an important cause of infertility: a review of literature. J Hum Reprod Sci. 2015;8(4):191-196. doi:10.4103/0974-1208.170370
Baker MA, Reeves G, Hetherington L, Müller J, Baur I, Aitken RJ. Identification of gene products present in Triton X-100 soluble and insoluble fractions of human spermatozoa lysates using LC-MS/MS analysis. Proteomics Clin Appl. 2007;1(5):524-532. doi:10.1002/prca.200601013
Wang G, Guo Y, Zhou T, et al. In-depth proteomic analysis of the human sperm reveals complex protein compositions. J Proteomics. 2013;79:114-122. doi:10.1016/j.jprot.2012.12.008
Amaral A, Castillo J, Ramalho-Santos J, Oliva R. The combined human sperm proteome: cellular pathways and implications for basic and clinical science. Hum Reprod Update. 2014;20(1):40-62. doi:10.1093/humupd/dmt046
Jodar M, Soler-Ventura A, Oliva R. Semen proteomics and male infertility. J Proteomics. 2017;162:125-134. doi:10.1016/j.jprot.2016.08.018
Castillo J, Jodar M, Oliva R. The contribution of human sperm proteins to the development and epigenome of the preimplantation embryo. Hum Reprod Update. 2018;24(5):535-555. doi:10.1093/humupd/dmy017
Bansal SK, Gupta N, Sankhwar SN, Rajender S. Differential genes expression between fertile and infertile spermatozoa revealed by transcriptome analysis. PLoS One. 2015;10(5):e0127007. doi:10.1371/journal.pone.0127007
Han B, Wang L, Yu S, et al. One potential biomarker for teratozoospermia identified by in-depth integrative analysis of multiple microarray data. Aging. 2021;13(7):10208-10224. doi:10.18632/aging.202781
Omolaoye TS, Hachim MY, Du Plessis SS. Using publicly available transcriptomic data to identify mechanistic and diagnostic biomarkers in azoospermia and overall male infertility. Sci Rep. 2022;12(1):2584. doi:10.1038/s41598-022-06476-1
O'Flynn O'Brien KL, Varghese AC, Agarwal A. The genetic causes of male factor infertility: a review. Fertil Steril. 2010;93(1):1-12. doi:10.1016/j.fertnstert.2009.10.045
Panner Selvam MK, Agarwal A. Update on the proteomics of male infertility: a systematic review. Arab J Urol. 2018;16(1):103-112. doi:10.1016/j.aju.2017.11.016
Krausz C, Riera-Escamilla A. Genetics of male infertility. Nat Rev Urol. 2018;15(6):369-384. doi:10.1038/s41585-018-0003-3
Greither T, Behre HM, Herlyn H. Genome-wide association screening determines peripheral players in male fertility maintenance. Int J Mol Sci. 2022;24(1):524. doi:10.3390/ijms24010524
Tahmasbpour E, Balasubramanian D, Agarwal A. A multi-faceted approach to understanding male infertility: gene mutations, molecular defects and assisted reproductive techniques (ART). J Assist Reprod Genet. 2014;31(9):1115-1137. doi:10.1007/s10815-014-0280-6
Leitão E, Di Persio S, Laurentino S, et al. The sperm epigenome does not display recurrent epimutations in patients with severely impaired spermatogenesis. Clin Epigenetics. 2020;12(1):61. doi:10.1186/s13148-020-00854-0
Schumacher J, Zischler H, Herlyn H. Effects of different kinds of essentiality on sequence evolution of human testis proteins. Sci Rep. 2017;7:43534. doi:10.1038/srep43534
Greither T, Schumacher J, Dejung M, et al. Fertility relevance probability analysis shortlists genetic markers for male fertility impairment. Cytogenet Genome Res. 2020;160(9):506-522. doi:10.1159/000511117
Liu X, Liu G, Liu J, et al. iTRAQ-based analysis of sperm proteome from normozoospermic men achieving the rescue-ICSI pregnancy after the IVF failure. Clin Proteomics. 2018;15:27. doi:10.1186/s12014-018-9203-3
Liang J, Zheng Y, Zeng W, et al. Proteomic profile of sperm in infertile males reveals changes in metabolic pathways. Protein J. 2021;40(6):929-939. doi:10.1007/s10930-021-10013-w
Yang J, Liu Q, Yu B, Han B, Yang B. 4D-quantitative proteomics signature of asthenozoospermia and identification of extracellular matrix protein 1 as a novel biomarker for sperm motility. Mol Omics. 2022;18(1):83-91. doi:10.1039/d1mo00257k
Bracke A, Peeters K, Punjabi U, Hoogewijs D, Dewilde S. A search for molecular mechanisms underlying male idiopathic infertility. Reprod Biomed Online. 2018;36(3):327-339. doi:10.1016/j.rbmo.2017.12.005
Deutsches IVF Register (D.I.R.). D.I.R. Jahrbuch 2009: Supplement 1. J Reproduktionsmed Endokrinol. 2010;7(6):470-497.
Cooper TG, Noonan E, von Eckardstein S, et al. World Health Organization reference values for human semen characteristics. Hum Reprod Update. 2010;16(3):231-245. doi:10.1093/humupd/dmp048
World Health Organization (WHO). WHO Laboratory Manual for the Examination and Processing of Human Semen. 6th ed. WHO; 2021.
Henkel R. Sperm preparation: state-of-the-art-physiological aspects and application of advanced sperm preparation methods. Asian J Androl. 2012;14(2):260-269. doi:10.1038/aja.2011.133
Panner Selvam MK, Agarwal A, Pushparaj PN, Baskaran S, Bendou H. Sperm proteome analysis and identification of fertility-associated biomarkers in unexplained male infertility. Genes. 2019;10(7):522. doi:10.3390/genes10070522
Parte PP, Rao P, Redij S, et al. Sperm phosphoproteome profiling by ultra performance liquid chromatography followed by data independent analysis (LC-MS(E)) reveals altered proteomic signatures in asthenozoospermia. J Proteomics. 2012;75(18):5861-5871. doi:10.1016/j.jprot.2012.07.003
Légaré C, Droit A, Fournier F, et al. Investigation of male infertility using quantitative comparative proteomics. J Proteome Res. 2014;13(12):5403-5414. doi:10.1021/pr501031x
Shevchenko A, Tomas H, Havlis J, Olsen JV, Mann M. In-gel digestion for mass spectrometric characterization of proteins and proteomes. Nat Protoc. 2006;1(6):2856-2860. doi:10.1038/nprot.2006.468
Rappsilber J, Mann M, Ishihama Y. Protocol for micro-purification, enrichment, pre-fractionation and storage of peptides for proteomics using StageTips. Nat Protoc. 2007;2(8):1896-1906. doi:10.1038/nprot.2007.261
Cox J, Mann M. MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification. Nat Biotechnol. 2008;26(12):1367-1372. doi:10.1038/nbt.1511
Ge SX, Jung D, Yao R. ShinyGO: a graphical gene-set enrichment tool for animals and plants. Bioinformatics. 2020;36(8):2628-2629. doi:10.1093/bioinformatics/btz931
Bindea G, Mlecnik B, Hackl H, et al. ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks. Bioinformatics. 2009;25(8):1091-1093. doi:10.1093/bioinformatics/btp101
Shannon P, Markiel A, Ozier O, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003;13(11):2498-2504. doi:10.1101/gr.1239303
Szklarczyk D, Gable AL, Lyon D, et al. STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res. 2019;47(D1):D607-D613. doi:10.1093/nar/gky1131
Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc. 1995;57(1):289-300.
Dai J, Zhang T, Guo J, et al. Homozygous pathogenic variants in ACTL9 cause fertilization failure and male infertility in humans and mice. Am J Hum Genet. 2021;108(3):469-481. doi:10.1016/j.ajhg.2021.02.004
Fan Y, Huang C, Chen J, et al. Mutations in CCIN cause teratozoospermia and male infertility. Sci Bull. 2022;67(20):2112-2123. doi:10.1016/j.scib.2022.09.026
Yan W. Calicin is a key sperm head-shaping factor essential for male fertility. Sci Bull. 2022;67(23):2395-2397. doi:10.1016/j.scib.2022.11.022
Liu C, Tu C, Wang L, et al. Deleterious variants in X-linked CFAP47 induce asthenoteratozoospermia and primary male infertility. Am J Hum Genet. 2021;108(2):309-323. doi:10.1016/j.ajhg.2021.01.002
Zhang X, Shen Y, Wang X, Yuan G, Zhang C, Yang Y. A novel homozygous CFAP65 mutation in humans causes male infertility with multiple morphological abnormalities of the sperm flagella. Clin Genet. 2019;96(6):541-548. doi:10.1111/cge.13644
Li W, Wu H, Li F, et al. Biallelic mutations in CFAP65 cause male infertility with multiple morphological abnormalities of the sperm flagella in humans and mice. J Med Genet. 2020;57(2):89-95. doi:10.1136/jmedgenet-2019-106344
Kherraf Z-E, Amiri-Yekta A, Dacheux D, et al. A homozygous ancestral SVA-insertion-mediated deletion in WDR66 induces multiple morphological abnormalities of the sperm flagellum and male infertility. Am J Hum Genet. 2018;103(3):400-412. doi:10.1016/j.ajhg.2018.07.014
Auguste Y, Delague V, Desvignes J-P, et al. Loss of calmodulin- and radial-spoke-associated complex protein CFAP251 leads to immotile spermatozoa lacking mitochondria and infertility in men. Am J Hum Genet. 2018;103(3):413-420. doi:10.1016/j.ajhg.2018.07.013
Zhuang B-J, Xu S-Y, Dong L, et al. Novel DNAH1 mutation loci lead to multiple morphological abnormalities of the sperm flagella and literature review. World J Mens Health. 2022;40(4):551-560. doi:10.5534/wjmh.210119
Hashemi M-S, Mozdarani H, Ghaedi K, Nasr-Esfahani MH. Among seven testis-specific molecular markers, SPEM1 appears to have a significant clinical value for prediction of sperm retrieval in azoospermic men. Andrology. 2018;6(6):890-895. doi:10.1111/andr.12528
Zheng H, Stratton CJ, Morozumi K, Jin J, Yanagimachi R, Yan W. Lack of Spem1 causes aberrant cytoplasm removal, sperm deformation, and male infertility. Proc Natl Acad Sci U S A. 2007;104(16):6852-6857. doi:10.1073/pnas.0701669104
Xin A, Qu R, Chen G, et al. Disruption in ACTL7A causes acrosomal ultrastructural defects in human and mouse sperm as a novel male factor inducing early embryonic arrest. Sci Adv. 2020;6(35):eaaz4796. doi:10.1126/sciadv.aaz4796
Wang J, Zhang J, Sun X, et al. Novel bi-allelic variants in ACTL7A are associated with male infertility and total fertilization failure. Hum Reprod. 2021;36(12):3161-3169. doi:10.1093/humrep/deab228
Ta-Shma A, Hjeij R, Perles Z, et al. Homozygous loss-of-function mutations in MNS1 cause laterality defects and likely male infertility. PLoS Genet. 2018;14(8):e1007602. doi:10.1371/journal.pgen.1007602
Leslie JS, Rawlins LE, Chioza BA, et al. MNS1 variant associated with situs inversus and male infertility. Eur J Hum Genet. 2020;28(1):50-55. doi:10.1038/s41431-019-0489-z
Wang F, Zhang J, Kong S, et al. A homozygous nonsense mutation of PLCZ1 cause male infertility with oocyte activation deficiency. J Assist Reprod Genet. 2020;37(4):821-828. doi:10.1007/s10815-020-01719-4
Zhu F, Liu C, Wang F, et al. Mutations in PMFBP1 cause acephalic spermatozoa syndrome. Am J Hum Genet. 2018;103(2):188-199. doi:10.1016/j.ajhg.2018.06.010
Nie H, Tang Y, Zhang X, Tan Y, Qin W. Novel mutations of PMFBP1 in a man with acephalic spermatozoa defects. Mol Genet Genomic Med. 2022;10(9):e2020. doi:10.1002/mgg3.2020
Deng T-Q, Xie Y-L, Pu J-B, Xuan J, Li X-M. Compound heterozygous mutations in PMFBP1 cause acephalic spermatozoa syndrome: a case report. World J Clin Cases. 2022;10(34):12761-12767. doi:10.12998/wjcc.v10.i34.12761
Kherraf Z-E, Cazin C, Coutton C, et al. Whole exome sequencing of men with multiple morphological abnormalities of the sperm flagella reveals novel homozygous QRICH2 mutations. Clin Genet. 2019;96(5):394-401. doi:10.1111/cge.13604
Shen Y, Zhang F, Li F, et al. Loss-of-function mutations in QRICH2 cause male infertility with multiple morphological abnormalities of the sperm flagella. Nat Commun. 2019;10(1):433. doi:10.1038/s41467-018-08182-x
Xu X, Sha Y-W, Mei L-B, et al. A familial study of twins with severe asthenozoospermia identified a homozygous SPAG17 mutation by whole-exome sequencing. Clin Genet. 2018;93(2):345-349. doi:10.1111/cge.13059
Zhou S, Wu H, Zhang J, et al. Bi-allelic variants in human TCTE1/DRC5 cause asthenospermia and male infertility. Eur J Hum Genet. 2022;30(6):721-729. doi:10.1038/s41431-022-01095-w
Tang S, Wang X, Li 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;100(6):854-864. doi:10.1016/j.ajhg.2017.04.012
Khan I, Shah B, Dil S, et al. Novel biallelic loss-of-function mutations in CFAP43 cause multiple morphological abnormalities of the sperm flagellum in Pakistani families. Asian J Androl. 2021;23(6):627-632. doi:10.4103/aja.aja_26_21
Lorès P, Coutton C, El Khouri E, et al. Homozygous missense mutation L673P in adenylate kinase 7 (AK7) leads to primary male infertility and multiple morphological anomalies of the flagella but not to primary ciliary dyskinesia. Hum Mol Genet. 2018;27(7):1196-1211. doi:10.1093/hmg/ddy034
Cavalcanti MCO, Steilmann C, Failing K, et al. Apoptotic gene expression in potentially fertile and subfertile men. Mol Hum Reprod. 2011;17(7):415-420. doi:10.1093/molehr/gar011
Arafat M, Harlev A, Har-Vardi I, et al. Mutation in CATIP (C2orf62) causes oligoteratoasthenozoospermia by affecting actin dynamics. J Med Genet. 2020. doi:10.1136/jmedgenet-2019-106825
Avidan N, Tamary H, Dgany O, et al. CATSPER2, a human autosomal nonsyndromic male infertility gene. Eur J Hum Genet. 2003;11(7):497-502. doi:10.1038/sj.ejhg.5200991
Luo T, Chen H-Y, Zou Q-X, et al. A novel copy number variation in CATSPER2 causes idiopathic male infertility with normal semen parameters. Hum Reprod. 2019;34(3):414-423. doi:10.1093/humrep/dey377
Kamel A, Saberiyan M, Mirfakhraie R, Teimori H. Reduced expression of CFAP44 and CFAP44-AS1 may affect sperm motility and morphology. Andrologia. 2022;54(7):e14447. doi:10.1111/and.14447
Ta-Shma A, Perles Z, Yaacov B, et al. A human laterality disorder associated with a homozygous WDR16 deletion. Eur J Hum Genet. 2015;23(9):1262-1265. doi:10.1038/ejhg.2014.265
Dougherty GW, Mizuno K, Nöthe-Menchen T, et al. CFAP45 deficiency causes situs abnormalities and asthenospermia by disrupting an axonemal adenine nucleotide homeostasis module. Nat Commun. 2020;11(1):5520. doi:10.1038/s41467-020-19113-0
He X, Liu C, Yang X, et al. Bi-allelic loss-of-function variants in CFAP58 cause flagellar axoneme and mitochondrial sheath defects and asthenoteratozoospermia in humans and mice. Am J Hum Genet. 2020;107(3):514-526. doi:10.1016/j.ajhg.2020.07.010
Dong FN, Amiri-Yekta A, Martinez G, 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;102(4):636-648. doi:10.1016/j.ajhg.2018.03.007
Beurois J, Martinez G, Cazin C, et al. CFAP70 mutations lead to male infertility due to severe astheno-teratozoospermia. A case report. Hum Reprod. 2019;34(10):2071-2079. doi:10.1093/humrep/dez166
Tu C, Cong J, Zhang Q, et al. Bi-allelic mutations of DNAH10 cause primary male infertility with asthenoteratozoospermia in humans and mice. Am J Hum Genet. 2021;108(8):1466-1477. doi:10.1016/j.ajhg.2021.06.010
Li K, Wang G, Lv M, et al. Bi-allelic variants in DNAH10 cause asthenoteratozoospermia and male infertility. J Assist Reprod Genet. 2022;39(1):251-259. doi:10.1007/s10815-021-02306-x
Whitfield M, Thomas L, Bequignon E, et al. Mutations in DNAH17, encoding a sperm-specific axonemal outer dynein arm heavy chain, cause isolated male infertility due to asthenozoospermia. Am J Hum Genet. 2019;105(1):198-212. doi:10.1016/j.ajhg.2019.04.015
Zhang B, Ma H, Khan T, et al. A DNAH17 missense variant causes flagella destabilization and asthenozoospermia. J Exp Med. 2020;217(2):e20182365. doi:10.1084/jem.20182365
Nosková A, Hiltpold M, Janett F, et al. Infertility due to defective sperm flagella caused by an intronic deletion in DNAH17 that perturbs splicing. Genetics. 2021;217(2):iyaa033. doi:10.1093/genetics/iyaa033
Martinez G, Kherraf Z-E, Zouari R, et al. Whole-exome sequencing identifies mutations in FSIP2 as a recurrent cause of multiple morphological abnormalities of the sperm flagella. Hum Reprod. 2018;33(10):1973-1984. doi:10.1093/humrep/dey264
Liu M, Sun Y, Li Y, Sun J, Yang Y, Shen Y. Novel mutations in FSIP2 lead to multiple morphological abnormalities of the sperm flagella and poor ICSI prognosis. Gene. 2021;781:145536. doi:10.1016/j.gene.2021.145536
Omolaoye TS, Omolaoye VA, Kandasamy RK, Hachim MY, Du Plessis SS. Omics and male infertility: highlighting the application of transcriptomic data. Life. 2022;12(2):280. doi:10.3390/life12020280
Nayernia K, Adham IM, Burkhardt-Göttges E, et al. Asthenozoospermia in mice with targeted deletion of the sperm mitochondrion-associated cysteine-rich protein (Smcp) gene. Mol Cell Biol. 2002;22(9):3046-3052. doi:10.1128/MCB.22.9.3046-3052.2002
Tu C, Nie H, Meng L, et al. Novel mutations in SPEF2 causing different defects between flagella and cilia bridge: the phenotypic link between MMAF and PCD. Hum Genet. 2020;139(2):257-271. doi:10.1007/s00439-020-02110-0
Lehti MS, Zhang F-P, Kotaja N, Sironen A. SPEF2 functions in microtubule-mediated transport in elongating spermatids to ensure proper male germ cell differentiation. Development. 2017;144(14):2683-2693. doi:10.1242/dev.152108
Zhu F, Wang F, Yang X, et al. Biallelic SUN5 mutations cause autosomal-recessive acephalic spermatozoa syndrome. Am J Hum Genet. 2016;99(6):1405. doi:10.1016/j.ajhg.2016.11.002
Xiang M, Wang Y, Wang K, et al. Novel mutation and deletion in SUN5 cause male infertility with acephalic spermatozoa syndrome. Reprod Sci. 2022;29(2):646-651. doi:10.1007/s43032-021-00665-5
Lorès P, Dacheux D, Kherraf Z-E, et al. Mutations in TTC29, encoding an evolutionarily conserved axonemal protein, result in asthenozoospermia and male infertility. Am J Hum Genet. 2019;105(6):1148-1167. doi:10.1016/j.ajhg.2019.10.007
Xu Y, Han Q, Ma C, et al. Comparative proteomics and phosphoproteomics analysis reveal the possible breed difference in yorkshire and duroc boar spermatozoa. Front Cell Dev Biol. 2021;9:652809. doi:10.3389/fcell.2021.652809
Dias TR, Agarwal A, Pushparaj PN, Ahmad G, Sharma R. Reduced semen quality in patients with testicular cancer seminoma is associated with alterations in the expression of sperm proteins. Asian J Androl. 2020;22(1):88-93. doi:10.4103/aja.aja_17_19
Wang Z, Ding Z, Guan Y, et al. Altered gene expression in the testis of infertile patients with nonobstructive azoospermia. Comput Math Methods Med. 2021;2021:5533483. doi:10.1155/2021/5533483
Hu T, Luo S, Xi Y, et al. Integrative bioinformatics approaches for identifying potential biomarkers and pathways involved in non-obstructive azoospermia. Transl Androl Urol. 2021;10(1):243-257. doi:10.21037/tau-20-1029
Platts AE, Dix DJ, Chemes HE, et al. Success and failure in human spermatogenesis as revealed by teratozoospermic RNAs. Hum Mol Genet. 2007;16(7):763-773. doi:10.1093/hmg/ddm012
Kui F, Ye H, Chen X-L, Zhang J. Microarray meta-analysis identifies candidate genes for human spermatogenic arrest. Andrologia. 2019;51(8):e13301. doi:10.1111/and.13301
Ing NH, Konganti K, Ghaffari N, et al. Identification and quantification of coding and long non-coding RNAs in stallion spermatozoa separated by density. Andrology. 2020;8(5):1409-1418. doi:10.1111/andr.12791
Zhang J, Yan R, Wu C, et al. Spermatogenesis-associated 48 is essential for spermatogenesis in mice. Andrologia. 2018;50(6):e13027. doi:10.1111/and.13027
Alvarez-Rodriguez M, Martinez C, Wright D, Barranco I, Roca J, Rodriguez-Martinez H. The transcriptome of pig spermatozoa, and its role in fertility. Int J Mol Sci. 2020;21(5):1572. doi:10.3390/ijms21051572
Schumacher J, Ramljak S, Asif AR, Schaffrath M, Zischler H, Herlyn H. Evolutionary conservation of mammalian sperm proteins associates with overall, not tyrosine, phosphorylation in human spermatozoa. J Proteome Res. 2013;12(12):5370-5382. doi:10.1021/pr400228c
Xin M, You S, Xu Y, et al. Precision glycoproteomics reveals distinctive N-glycosylation in human spermatozoa. Mol Cell Proteomics. 2022;21(4):100214. doi:10.1016/j.mcpro.2022.100214
LaMunyon CW, Ward S. Evolution of larger sperm in response to experimentally increased sperm competition in Caenorhabditis elegans. Proc Biol Sci. 2002;269(1496):1125-1128. doi:10.1098/rspb.2002.1996
Tourmente M, Gomendio M, Roldan ERS. Sperm competition and the evolution of sperm design in mammals. BMC Evol Biol. 2011;11:12. doi:10.1186/1471-2148-11-12
Lüke L, Vicens A, Tourmente M, Roldan ERS. Evolution of protamine genes and changes in sperm head phenotype in rodents. Biol Reprod. 2014;90(3):67. doi:10.1095/biolreprod.113.115956
Cohen-Dayag A, Ralt D, Tur-Kaspa I, et al. Sequential acquisition of chemotactic responsiveness by human spermatozoa. Biol Reprod. 1994;50(4):786-790. doi:10.1095/biolreprod50.4.786
Primakoff P, Myles DG. Penetration, adhesion, and fusion in mammalian sperm-egg interaction. Science. 2002;296(5576):2183-2185. doi:10.1126/science.1072029
Chakradhar S. Puzzling over privilege: how the immune system protects-and fails-the testes. Nat Med. 2018;24(1):2-5. doi:10.1038/nm0118-2
Wang X, Jiang C, Dai S, Shen G, Yang Y, Shen Y. Identification of nonfunctional SPATA20 causing acephalic spermatozoa syndrome in humans. Clin Genet. 2023;103(3):310-319. doi:10.1111/cge.14268
Lin Y-N, Roy A, Yan W, Burns KH, Matzuk MM. Loss of zona pellucida binding proteins in the acrosomal matrix disrupts acrosome biogenesis and sperm morphogenesis. Mol Cell Biol. 2007;27(19):6794-6805. doi:10.1128/MCB.01029-07
Yeh C-H, Kuo P-L, Wang Y-Y, et al. SEPT12/SPAG4/LAMINB1 complexes are required for maintaining the integrity of the nuclear envelope in postmeiotic male germ cells. PLoS One. 2015;10(3):e0120722. doi:10.1371/journal.pone.0120722
Gilany K, Lakpour N, Vafakhah M, Sadeghi MR. The profile of human sperm proteome; a mini-review. J Reprod Infertil. 2011;12(3):193-199.
Balbach M, Beckert V, Hansen JN, Wachten D. Shedding light on the role of cAMP in mammalian sperm physiology. Mol Cell Endocrinol. 2018;468:111-120. doi:10.1016/j.mce.2017.11.008
Jimenez T, McDermott JP, Sánchez G, Blanco G. Na,K-ATPase alpha4 isoform is essential for sperm fertility. Proc Natl Acad Sci U S A. 2011;108(2):644-649. doi:10.1073/pnas.1016902108
Curi SM, Ariagno JI, Chenlo PH, et al. Asthenozoospermia: analysis of a large population. Arch Androl. 2003;49(5):343-349. doi:10.1080/01485010390219656
Oseguera-López I, Ruiz-Díaz S, Ramos-Ibeas P, Pérez-Cerezales S. Novel techniques of sperm selection for improving IVF and ICSI outcomes. Front Cell Dev Biol. 2019;7:298. doi:10.3389/fcell.2019.00298
Villani MT, Morini D, Spaggiari G, et al. Are sperm parameters able to predict the success of assisted reproductive technology? A retrospective analysis of over 22,000 assisted reproductive technology cycles. Andrology. 2022;10(2):310-321. doi:10.1111/andr.13123
Ferlin A, Raicu F, Gatta V, Zuccarello D, Palka G, Foresta C. Male infertility: role of genetic background. Reprod Biomed Online. 2007;14(6):734-745. doi:10.1016/s1472-6483(10)60677-3
Cox LJ, Larman MG, Saunders CM, Hashimoto K, Swann K, Lai FA. Sperm phospholipase Czeta from humans and cynomolgus monkeys triggers Ca2+ oscillations, activation and development of mouse oocytes. Reproduction. 2002;124(5):611-623. doi:10.1530/rep.0.1240611
Rogers NT, Hobson E, Pickering S, Lai FA, Braude P, Swann K. Phospholipase Czeta causes Ca2+ oscillations and parthenogenetic activation of human oocytes. Reproduction. 2004;128(6):697-702. doi:10.1530/rep.1.00484
Escoffier J, Lee HC, Yassine S, et al. Homozygous mutation of PLCZ1 leads to defective human oocyte activation and infertility that is not rescued by the WW-binding protein PAWP. Hum Mol Genet. 2016;25(5):878-891. doi:10.1093/hmg/ddv617
Govindaraju A, Dogan S, Rodriguez-Osorio N, Grant K, Kaya A, Memili E. Delivering value from sperm proteomics for fertility. Cell Tissue Res. 2012;349(3):783-793. doi:10.1007/s00441-012-1452-2
Hu Y, Benedict MA, Ding L, Núñez G. Role of cytochrome c and dATP/ATP hydrolysis in Apaf-1-mediated caspase-9 activation and apoptosis. EMBO J. 1999;18(13):3586-3595. doi:10.1093/emboj/18.13.3586
Lécuyer C, Dacheux JL, Hermand E, Mazeman E, Rousseaux J, Rousseaux-Prévost R. Actin-binding properties and colocalization with actin during spermiogenesis of mammalian sperm calicin. Biol Reprod. 2000;63(6):1801-1810. doi:10.1095/biolreprod63.6.1801
von Bülow M, Heid H, Hess H, Franke WW. Molecular nature of calicin, a major basic protein of the mammalian sperm head cytoskeleton. Exp Cell Res. 1995;219(2):407-413. doi:10.1006/excr.1995.1246
Ben Khelifa M, Coutton C, Zouari R, 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;94(1):95-104. doi:10.1016/j.ajhg.2013.11.017
Levkova M, Radanova M, Angelova L. Potential role of dynein-related genes in the etiology of male infertility: a systematic review and a meta-analysis. Andrology. 2022;10(8):1484-1499. doi:10.1111/andr.13287
Davis FM, Goulding EH, D'Agostin DM, et al. Male infertility in mice lacking the store-operated Ca(2+) channel Orai1. Cell Calcium. 2016;59(4):189-197. doi:10.1016/j.ceca.2016.02.007
Albarran L, Lopez JJ, Jardin I, et al. EFHB is a novel cytosolic Ca2+ sensor that modulates STIM1-SARAF interaction. Cell Physiol Biochem. 2018;51(3):1164-1178. doi:10.1159/000495494
Di Gioia SA, Letteboer SJF, Kostic C, et al. FAM161A, associated with retinitis pigmentosa, is a component of the cilia-basal body complex and interacts with proteins involved in ciliopathies. Hum Mol Genet. 2012;21(23):5174-5184. doi:10.1093/hmg/dds368
Khanal S, Leung MR, Royfman A, et al. A dynamic basal complex modulates mammalian sperm movement. Nat Commun. 2021;12(1):3808. doi:10.1038/s41467-021-24011-0
Hess H, Heid H, Franke WW. Molecular characterization of mammalian cylicin, a basic protein of the sperm head cytoskeleton. J Cell Biol. 1993;122(5):1043-1052. doi:10.1083/jcb.122.5.1043
Panner Selvam MK, Agarwal A. Update on the proteomics of male infertility: a systematic review. Arab J Urol. 2018;16(1):103-112. doi:10.1016/j.aju.2017.11.016
Gilany K, Minai-Tehrani A, Savadi-Shiraz E, Rezadoost H, Lakpour N. Exploring the human seminal plasma proteome: an unexplored gold mine of biomarker for male infertility and male reproduction disorder. J Reprod Infertil. 2015;16(2):61-71.
Martins AD, Panner Selvam MK, Agarwal A, Alves MG, Baskaran S. Alterations in seminal plasma proteomic profile in men with primary and secondary infertility. Sci Rep. 2020;10(1):7539. doi:10.1038/s41598-020-64434-1
Agarwal A, Bertolla RP, Samanta L. Sperm proteomics: potential impact on male infertility treatment. Expert Rev Proteomics. 2016;13(3):285-296. doi:10.1586/14789450.2016.1151357