{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T17:26:43Z","timestamp":1785346003381,"version":"3.55.0"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2022,12,26]],"date-time":"2022-12-26T00:00:00Z","timestamp":1672012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Clinical Medical Technology Innovation Guidance Project of Hunan Province","award":["2021SK53716"],"award-info":[{"award-number":["2021SK53716"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,12,28]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Spermatogenesis is a complex process that includes spermatogonia self-renewal, spermatocyte meiosis and spermatozoa assembly. Recent studies have revealed that WD40-repeat domain-containing (WDR) proteins play important roles in spermatocyte division, spermatozoa flagella assembly and head shaping. In this study, we investigated the expression pattern of WDR87 and found that it was highly expressed in the testis of both humans and mice. Immunofluorescence staining revealed that mouse WDR87 was distributed in the perinuclear cytoplasm of primary spermatocytes, secondary spermatocytes and round spermatids. In the spermiogenesis stage, with extension of the nucleus, WDR87 migrated to the manchette and finally localized to the middle piece of the spermatozoa tail. Furthermore, we identified a cilia- and flagella-associated protein, CFAP47, which interacted with WDR87 in the flagellar midpiece of the spermatozoa, suggesting that WDR87 may be associated with multiple morphological abnormalities of the flagella (MMAF). Subsequently, we screened gene mutations in seven MMAF individuals and found two novel mutations in CFAP47 (c.706G&amp;gt;A, Val236Met; c.1337C&amp;gt;T, Thr446Met) in one case. Immunoblotting and immunofluorescence revealed that CFAP47 was dramatically reduced in spermatozoa from the CFAP47-mutated man. Meanwhile, the expression of WDR87 was also significantly decreased, and weak signals were detected adjacent to the spermatozoa nuclei, indicating that CFAP47 was necessary for WDR87 transportation during spermatozoa flagella biogenesis. These data indicate that WDR87 is located in the middle piece of the sperm tail and interacts with CFAP47 to form a complex which is involved in spermatozoa tail assembly.<\/jats:p>","DOI":"10.1093\/molehr\/gaac042","type":"journal-article","created":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T23:46:27Z","timestamp":1671839187000},"source":"Crossref","is-referenced-by-count":16,"title":["WDR87 interacts with CFAP47 protein in the middle piece of spermatozoa flagella to participate in sperm tail assembly"],"prefix":"10.1093","volume":"29","author":[{"given":"Hong-qing","family":"Liao","sequence":"first","affiliation":[{"name":"The Second Affiliated Hospital, Hengyang Medical School, University of South China , Hengyang, China"},{"name":"Hengyang Nanhua-Xinghui Reproductive Health Hospital , Hengyang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4713-1094","authenticated-orcid":false,"given":"Zi-yi","family":"Guo","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital, Hengyang Medical School, University of South China , Hengyang, China"},{"name":"Hengyang Nanhua-Xinghui Reproductive Health Hospital , Hengyang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-hua","family":"Huang","sequence":"additional","affiliation":[{"name":"Center for Experimental Medicine, Third Xiangya Hospital, Central South University , Changsha, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Liu","sequence":"additional","affiliation":[{"name":"The Institute of Reproduction and Stem Cell Engineering, School of Basic Medical Science, Central South University , Changsha, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-feng","family":"Lu","sequence":"additional","affiliation":[{"name":"Hengyang Nanhua-Xinghui Reproductive Health Hospital , Hengyang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun-fei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center for Experimental Medicine, Third Xiangya Hospital, Central South University , Changsha, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5648-8864","authenticated-orcid":false,"given":"Xiao-wei","family":"Xing","sequence":"additional","affiliation":[{"name":"Center for Experimental Medicine, Third Xiangya Hospital, Central South University , Changsha, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,12,26]]},"reference":[{"key":"2023010806124643700_gaac042-B1","doi-asserted-by":"crossref","DOI":"10.1002\/0471142905.hg0720s76","article-title":"Predicting functional effect of human missense mutations using PolyPhen-2","author":"Adzhubei","year":"2013","journal-title":"Curr Protoc Hum Genet"},{"key":"2023010806124643700_gaac042-B2","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/S0140-6736(20)32667-2","article-title":"Male infertility","volume":"397","author":"Agarwal","year":"2021","journal-title":"Lancet"},{"key":"2023010806124643700_gaac042-B3","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.ajhg.2018.07.013","article-title":"Loss of calmodulin- and radial-spoke-associated complex protein CFAP251 leads to immotile spermatozoa lacking mitochondria and infertility in men","volume":"103","author":"Auguste","year":"2018","journal-title":"Am J Hum Genet"},{"key":"2023010806124643700_gaac042-B4","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.ajhg.2013.11.017","article-title":"Mutations in DNAH1, which encodes an inner arm heavy chain dynein, lead to male infertility from multiple morphological abnormalities of the sperm flagella","volume":"94","author":"Ben Khelifa","year":"2014","journal-title":"Am J Hum Genet"},{"key":"2023010806124643700_gaac042-B5","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.3390\/ijms21051728","article-title":"Molecular biology of spermatogenesis: novel targets of apparently idiopathic male infertility","volume":"21","author":"Cannarella","year":"2020","journal-title":"Int J Mol Sci"},{"key":"2023010806124643700_gaac042-B6","first-page":"626","article-title":"Whole-exome enrichment with the Agilent SureSelect Human All Exon Platform","volume":"2015","author":"Chen","year":"2015","journal-title":"Cold Spring Harb Protoc"},{"key":"2023010806124643700_gaac042-B7","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1038\/s41467-017-02792-7","article-title":"Mutations in CFAP43 and CFAP44 cause male infertility and flagellum defects in Trypanosoma and human","volume":"9","author":"Coutton","year":"2018","journal-title":"Nat Commun"},{"key":"2023010806124643700_gaac042-B8","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1093\/molehr\/gau018","article-title":"The human testis-specific proteome defined by transcriptomics and antibody-based profiling","volume":"20","author":"Djureinovic","year":"2014","journal-title":"Mol Hum Reprod"},{"key":"2023010806124643700_gaac042-B9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1152\/physrev.00013.2015","article-title":"Spermatogenesis: the commitment to meiosis","volume":"96","author":"Griswold","year":"2016","journal-title":"Physiol Rev"},{"key":"2023010806124643700_gaac042-B10","doi-asserted-by":"crossref","first-page":"e202007171","DOI":"10.1083\/jcb.202007171","article-title":"WDR62 localizes katanin at spindle poles to ensure synchronous chromosome segregation","volume":"220","author":"Guerreiro","year":"2021","journal-title":"J Cell Biol"},{"key":"2023010806124643700_gaac042-B11","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1093\/molehr\/gah163","article-title":"Patterns of expression of sperm flagellar genes: early expression of genes encoding axonemal proteins during the spermatogenic cycle and shared features of promoters of genes encoding central apparatus proteins","volume":"11","author":"Horowitz","year":"2005","journal-title":"Mol Hum Reprod"},{"key":"2023010806124643700_gaac042-B12","doi-asserted-by":"crossref","first-page":"e202007167","DOI":"10.1083\/jcb.202007167","article-title":"WDR62 regulates spindle dynamics as an adaptor protein between TPX2\/Aurora A and katanin","volume":"220","author":"Huang","year":"2021","journal-title":"J Cell Biol"},{"key":"2023010806124643700_gaac042-B13","doi-asserted-by":"crossref","first-page":"662903","DOI":"10.3389\/fcell.2021.662903","article-title":"Genetic defects in DNAH2 underlie male infertility with multiple morphological abnormalities of the sperm flagella in humans and mice","volume":"9","author":"Hwang","year":"2021","journal-title":"Front Cell Dev Biol"},{"key":"2023010806124643700_gaac042-B14","doi-asserted-by":"crossref","first-page":"3659","DOI":"10.1242\/dev.152413","article-title":"Unraveling transcriptome dynamics in human spermatogenesis","volume":"144","author":"Jan","year":"2017","journal-title":"Development (Cambridge, England)"},{"key":"2023010806124643700_gaac042-B15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/mrd.10179","article-title":"Intramanchette transport (IMT): managing the making of the spermatid head, centrosome, and tail","volume":"63","author":"Kierszenbaum","year":"2002","journal-title":"Mol Reprod Dev"},{"key":"2023010806124643700_gaac042-B16","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1038\/nprot.2009.86","article-title":"Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm","volume":"4","author":"Kumar","year":"2009","journal-title":"Nat Protoc"},{"key":"2023010806124643700_gaac042-B17","doi-asserted-by":"crossref","first-page":"R43","DOI":"10.1530\/REP-15-0310","article-title":"Formation and function of the manchette and flagellum during spermatogenesis","volume":"151","author":"Lehti","year":"2016","journal-title":"Reproduction"},{"key":"2023010806124643700_gaac042-B18","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/s10038-021-00985-z","article-title":"DRC1 deficiency caused primary ciliary dyskinesia and MMAF in a Chinese patient","volume":"67","author":"Lei","year":"2022","journal-title":"J Hum Genet"},{"key":"2023010806124643700_gaac042-B19","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1007\/s10815-021-02306-x","article-title":"Bi-allelic variants in DNAH10 cause asthenoteratozoospermia and male infertility","volume":"39","author":"Li","year":"2022","journal-title":"J Assist Reprod Genet"},{"key":"2023010806124643700_gaac042-B20","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/s10038-018-0520-1","article-title":"Biallelic mutations of CFAP251 cause sperm flagellar defects and human male infertility","volume":"64","author":"Li","year":"2019","journal-title":"J Hum Genet"},{"key":"2023010806124643700_gaac042-B21","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1093\/abbs\/gmz051","article-title":"SPAG4L\/SPAG4Lbeta interacts with Nesprin2 to participate in the meiosis of spermatogenesis","volume":"51","author":"Li","year":"2019","journal-title":"Acta Biochim Biophys Sin (Shanghai)"},{"key":"2023010806124643700_gaac042-B22","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.ajhg.2021.01.002","article-title":"Deleterious variants in X-linked CFAP47 induce asthenoteratozoospermia and primary male infertility","volume":"108","author":"Liu","year":"2021","journal-title":"Am J Hum Genet"},{"key":"2023010806124643700_gaac042-B23","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1038\/s41419-021-03755-z","article-title":"Loss of CEP70 function affects acrosome biogenesis and flagella formation during spermiogenesis","volume":"12","author":"Liu","year":"2021","journal-title":"Cell Death Dis"},{"key":"2023010806124643700_gaac042-B24","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1038\/s41421-021-00327-5","article-title":"Bi-allelic variants in human WDR63 cause male infertility via abnormal inner dynein arms assembly","volume":"7","author":"Lu","year":"2021","journal-title":"Cell Discov"},{"key":"2023010806124643700_gaac042-B25","doi-asserted-by":"crossref","first-page":"803818","DOI":"10.3389\/fcell.2021.803818","article-title":"Biallelic variants in CFAP61 cause multiple morphological abnormalities of the flagella and male infertility","volume":"9","author":"Ma","year":"2021","journal-title":"Front Cell Dev Biol"},{"key":"2023010806124643700_gaac042-B26","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/aja.2009.14","article-title":"Clinical significance of the low normal sperm morphology value as proposed in the fifth edition of the WHO Laboratory Manual for the Examination and Processing of Human Semen","volume":"12","author":"Menkveld","year":"2010","journal-title":"Asian J Androl"},{"key":"2023010806124643700_gaac042-B27","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1186\/s12864-020-07016-9","article-title":"Expression profiling of WD40 family genes including DDB1- and CUL4- associated factor (DCAF) genes in mice and human suggests important regulatory roles in testicular development and spermatogenesis","volume":"21","author":"Mistry","year":"2020","journal-title":"BMC Genomics"},{"key":"2023010806124643700_gaac042-B28","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.semcdb.2016.04.009","article-title":"Spermatogenesis in humans and its affecting factors","volume":"59","author":"Neto","year":"2016","journal-title":"Semin Cell Dev Biol"},{"key":"2023010806124643700_gaac042-B29","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1007\/s10815-020-01770-1","article-title":"A novel homozygous mutation in WDR19 induces disorganization of microtubules in sperm flagella and nonsyndromic asthenoteratospermia","volume":"37","author":"Ni","year":"2020","journal-title":"J Assist Reprod Genet"},{"key":"2023010806124643700_gaac042-B30","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/s00439-016-1747-6","article-title":"Novel phenotypes and loci identified through clinical genomics approaches to pediatric cataract","volume":"136","author":"Patel","year":"2017","journal-title":"Hum Genet"},{"key":"2023010806124643700_gaac042-B31","doi-asserted-by":"crossref","first-page":"dev174128","DOI":"10.1242\/dev.174128","article-title":"WDR62 is involved in spindle assembly by interacting with CEP170 in spermatogenesis","volume":"146","author":"Qin","year":"2019","journal-title":"Development"},{"key":"2023010806124643700_gaac042-B32","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1038\/nrm952","article-title":"Intraflagellar transport","volume":"3","author":"Rosenbaum","year":"2002","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2023010806124643700_gaac042-B33","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1038\/nrd.2017.179","article-title":"WD40 repeat domain proteins: a novel target class?","volume":"16","author":"Schapira","year":"2017","journal-title":"Nat Rev Drug Discov"},{"key":"2023010806124643700_gaac042-B34","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/nmeth.2890","article-title":"MutationTaster2: mutation prediction for the deep-sequencing age","volume":"11","author":"Schwarz","year":"2014","journal-title":"Nat Methods"},{"key":"2023010806124643700_gaac042-B35","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1038\/s10038-020-0790-2","article-title":"Biallelic mutations of CFAP74 may cause human primary ciliary dyskinesia and MMAF phenotype","volume":"65","author":"Sha","year":"2020","journal-title":"J Hum Genet"},{"key":"2023010806124643700_gaac042-B36","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1016\/j.ajhg.2017.04.012","article-title":"Biallelic mutations in CFAP43 and CFAP44 cause male infertility with multiple morphological abnormalities of the sperm flagella","volume":"100","author":"Tang","year":"2017","journal-title":"Am J Hum Genet"},{"key":"2023010806124643700_gaac042-B37","doi-asserted-by":"crossref","first-page":"14240","DOI":"10.1038\/s41598-020-71120-9","article-title":"The WD40-protein CFAP52\/WDR16 is a centrosome\/basal body protein and localizes to the manchette and the flagellum in male germ cells","volume":"10","author":"Tapia Contreras","year":"2020","journal-title":"Sci Rep"},{"key":"2023010806124643700_gaac042-B38","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1016\/S2213-8587(16)30040-7","article-title":"Novel concepts in the aetiology of male reproductive impairment","volume":"5","author":"Tournaye","year":"2017","journal-title":"Lancet Diabetes Endocrinol"},{"key":"2023010806124643700_gaac042-B39","doi-asserted-by":"crossref","first-page":"e164","DOI":"10.1093\/nar\/gkq603","article-title":"ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data","volume":"38","author":"Wang","year":"2010","journal-title":"Nucleic Acids Res"},{"key":"2023010806124643700_gaac042-B40","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/j.stem.2018.08.007","article-title":"Single-cell RNA sequencing analysis reveals sequential cell fate transition during human spermatogenesis","volume":"23","author":"Wang","year":"2018","journal-title":"Cell Stem Cell"},{"key":"2023010806124643700_gaac042-B41","doi-asserted-by":"crossref","first-page":"676910","DOI":"10.3389\/fcell.2021.676910","article-title":"Essential role of CFAP53 in sperm flagellum biogenesis","volume":"9","author":"Wu","year":"2021","journal-title":"Front Cell Dev Biol"},{"key":"2023010806124643700_gaac042-B42","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1007\/s10815-021-02363-2","article-title":"A novel homozygous missense mutation in AK7 causes multiple morphological anomalies of the flagella and oligoasthenoteratozoospermia","volume":"39","author":"Xiang","year":"2022","journal-title":"J Assist Reprod Genet"},{"key":"2023010806124643700_gaac042-B43","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1007\/s13238-011-1018-1","article-title":"Structure and function of WD40 domain proteins","volume":"2","author":"Xu","year":"2011","journal-title":"Protein Cell"},{"key":"2023010806124643700_gaac042-B44","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/s12958-022-00916-3","article-title":"Homozygous SPAG6 variants can induce nonsyndromic asthenoteratozoospermia with severe MMAF","volume":"20","author":"Xu","year":"2022","journal-title":"Reprod Biol Endocrinol"},{"key":"2023010806124643700_gaac042-B45","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1007\/s11684-021-0851-8","article-title":"DDB1- and CUL4-associated factor 8 plays a critical role in spermatogenesis","volume":"15","author":"Zhang","year":"2021","journal-title":"Front Med"},{"key":"2023010806124643700_gaac042-B46","doi-asserted-by":"crossref","first-page":"684826","DOI":"10.3389\/fcell.2021.684826","article-title":"SUN5 interacting with Nesprin3 plays an essential role in sperm head-to-tail linkage: research on Sun5 gene knockout mice","volume":"9","author":"Zhang","year":"2021","journal-title":"Front Cell Dev Biol"},{"key":"2023010806124643700_gaac042-B47","doi-asserted-by":"crossref","first-page":"463","DOI":"10.4103\/aja202183","article-title":"Novel mutation in ODF2 causes multiple morphological abnormalities of the sperm flagella in an infertile male","volume":"24","author":"Zhu","year":"2022","journal-title":"Asian J Androl"}],"container-title":["Molecular Human Reproduction"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/molehr\/advance-article-pdf\/doi\/10.1093\/molehr\/gaac042\/48416523\/gaac042.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/molehr\/article-pdf\/29\/1\/gaac042\/48521682\/gaac042.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/molehr\/article-pdf\/29\/1\/gaac042\/48521682\/gaac042.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,10]],"date-time":"2024-10-10T23:23:16Z","timestamp":1728602596000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/molehr\/article\/doi\/10.1093\/molehr\/gaac042\/6960929"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,26]]},"references-count":47,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,12,28]]}},"URL":"https:\/\/doi.org\/10.1093\/molehr\/gaac042","relation":{},"ISSN":["1460-2407"],"issn-type":[{"value":"1460-2407","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,1,1]]},"published":{"date-parts":[[2022,12,26]]},"article-number":"gaac042"}}