{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T23:38:45Z","timestamp":1789169925900,"version":"build-2803163510"},"reference-count":74,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,11,17]],"date-time":"2017-11-17T00:00:00Z","timestamp":1510876800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,11,17]],"date-time":"2017-11-17T00:00:00Z","timestamp":1510876800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Spermatogenesis is a multifactorial process that forms differentiated sperm cells in a complex microenvironment. This process involves the genome, epigenome, transcriptome, and proteome to ensure the stability of the spermatogonia and supporting cells. The identification of signaling pathways linked to infertility has been hampered by the inherent complexity and multifactorial aspects of spermatogenesis. Systems biology is a promising approach to unveil underlying signaling pathways and genes and identify putative biomarkers. In this study, we analyzed thirteen microarray libraries of infertile humans and mice, and different classes of male infertility were compared using differentially expressed genes and functional enrichment analysis. We found regulatory processes, immune response, glutathione transferase and muscle tissue development to be among the most common biological processes in up-regulated genes, and genes involved in spermatogenesis were down-regulated in maturation arrest (MArrest) and oligospermia cases. We also observed the overexpression of genes involved in steroid metabolism in post-meiotic and meiotic arrest. Furthermore, we found that the infertile mouse model most similar to human MArrest was the <jats:italic>Dazap1<\/jats:italic> mutant mouse. The results of this study could help elucidate features of infertility etiology and provide the basis for diagnostic markers.<\/jats:p>","DOI":"10.1038\/s41598-017-16005-0","type":"journal-article","created":{"date-parts":[[2017,11,13]],"date-time":"2017-11-13T10:23:36Z","timestamp":1510568616000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Comprehensive functional enrichment analysis of male infertility"],"prefix":"10.1038","volume":"7","author":[{"given":"Seyed Morteza","family":"Razavi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjan","family":"Sabbaghian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahdi","family":"Jalili","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adeleh","family":"Divsalar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olaf","family":"Wolkenhauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Salehzadeh-Yazdi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,11,17]]},"reference":[{"key":"16005_CR1","doi-asserted-by":"publisher","first-page":"1144","DOI":"10.1093\/humrep\/deh870","volume":"20","author":"C Gnoth","year":"2005","unstructured":"Gnoth, C. et al. Definition and prevalence of subfertility and infertility. Hum Reprod \n                           20, 1144\u20131147, https:\/\/doi.org\/10.1093\/humrep\/deh870 (2005).","journal-title":"Hum Reprod"},{"key":"16005_CR2","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1038\/aja.2011.67","volume":"14","author":"A Massart","year":"2012","unstructured":"Massart, A., Lissens, W., Tournaye, H. & Stouffs, K. Genetic causes of spermatogenic failure. Asian journal of andrology \n                           14, 40\u201348, https:\/\/doi.org\/10.1038\/aja.2011.67 (2012).","journal-title":"Asian journal of andrology"},{"key":"16005_CR3","doi-asserted-by":"publisher","first-page":"1115","DOI":"10.1007\/s10815-014-0280-6","volume":"31","author":"E Tahmasbpour","year":"2014","unstructured":"Tahmasbpour, E., Balasubramanian, D. & Agarwal, A. A multi-faceted approach to understanding male infertility: gene mutations, molecular defects and assisted reproductive techniques (ART). Journal of assisted reproduction and genetics \n                           31, 1115\u20131137, https:\/\/doi.org\/10.1007\/s10815-014-0280-6 (2014).","journal-title":"Journal of assisted reproduction and genetics"},{"key":"16005_CR4","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1111\/j.1745-7262.2006.00123.x","volume":"8","author":"G Cavallini","year":"2006","unstructured":"Cavallini, G. Male idiopathic oligoasthenoteratozoospermia. Asian journal of andrology \n                           8, 143\u2013157, https:\/\/doi.org\/10.1111\/j.1745-7262.2006.00123.x (2006).","journal-title":"Asian journal of andrology"},{"key":"16005_CR5","first-page":"336","volume":"50","author":"J Poongothai","year":"2009","unstructured":"Poongothai, J., Gopenath, T. S. & Manonayaki, S. Genetics of human male infertility. Singapore medical journal \n                           50, 336\u2013347 (2009).","journal-title":"Singapore medical journal"},{"key":"16005_CR6","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1093\/humupd\/dmp048","volume":"16","author":"TG Cooper","year":"2010","unstructured":"Cooper, T. G. et al. World Health Organization reference values for human semen characteristics. Human reproduction update \n                           16, 231\u2013245, https:\/\/doi.org\/10.1093\/humupd\/dmp048 (2010).","journal-title":"Human reproduction update"},{"key":"16005_CR7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ucl.2013.08.009","volume":"41","author":"JM Hotaling","year":"2014","unstructured":"Hotaling, J. M. Genetics of male infertility. The Urologic clinics of North America \n                           41, 1\u201317, https:\/\/doi.org\/10.1016\/j.ucl.2013.08.009 (2014).","journal-title":"The Urologic clinics of North America"},{"key":"16005_CR8","doi-asserted-by":"publisher","first-page":"R159","DOI":"10.1530\/REP-15-0261","volume":"150","author":"C Krausz","year":"2015","unstructured":"Krausz, C., Escamilla, A. R. & Chianese, C. Genetics of male infertility: from research to clinic. Reproduction \n                           150, R159\u2013174, https:\/\/doi.org\/10.1530\/REP-15-0261 (2015).","journal-title":"Reproduction"},{"key":"16005_CR9","doi-asserted-by":"publisher","first-page":"176","DOI":"10.4103\/0974-1208.121419","volume":"6","author":"SC Esteves","year":"2013","unstructured":"Esteves, S. C. A clinical appraisal of the genetic basis in unexplained male infertility. Journal of human reproductive sciences \n                           6, 176\u2013182, https:\/\/doi.org\/10.4103\/0974-1208.121419 (2013).","journal-title":"Journal of human reproductive sciences"},{"issue":"Suppl 1","key":"16005_CR10","doi-asserted-by":"publisher","first-page":"39","DOI":"10.6061\/clinics\/2013(Sup01)06","volume":"68","author":"AJ Hamada","year":"2013","unstructured":"Hamada, A. J., Esteves, S. C. & Agarwal, A. A comprehensive review of genetics and genetic testing in azoospermia. Clinics (Sao Paulo) \n                           68(Suppl 1), 39\u201360 (2013).","journal-title":"Clinics (Sao Paulo)"},{"key":"16005_CR11","doi-asserted-by":"publisher","first-page":"1501","DOI":"10.1098\/rstb.2009.0124","volume":"365","author":"C Shaha","year":"2010","unstructured":"Shaha, C., Tripathi, R. & Mishra, D. P. Male germ cell apoptosis: regulation and biology. Philosophical transactions of the Royal Society of London. Series B, Biological sciences \n                           365, 1501\u20131515, https:\/\/doi.org\/10.1098\/rstb.2009.0124 (2010).","journal-title":"Philosophical transactions of the Royal Society of London. Series B, Biological sciences"},{"key":"16005_CR12","doi-asserted-by":"publisher","first-page":"1197","DOI":"10.1038\/nm.f.1895","volume":"14","author":"MM Matzuk","year":"2008","unstructured":"Matzuk, M. M. & Lamb, D. J. The biology of infertility: research advances and clinical challenges. Nature medicine \n                           14, 1197\u20131213, https:\/\/doi.org\/10.1038\/nm.f.1895 (2008).","journal-title":"Nature medicine"},{"key":"16005_CR13","doi-asserted-by":"publisher","first-page":"e28218","DOI":"10.4161\/spmg.28218","volume":"4","author":"M Wosnitzer","year":"2014","unstructured":"Wosnitzer, M., Goldstein, M. & Hardy, M. P. Review of Azoospermia. Spermatogenesis \n                           4, e28218, https:\/\/doi.org\/10.4161\/spmg.28218 (2014).","journal-title":"Spermatogenesis"},{"key":"16005_CR14","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1007\/s10815-015-0433-2","volume":"32","author":"M De Braekeleer","year":"2015","unstructured":"De Braekeleer, M., Nguyen, M. H., Morel, F. & Perrin, A. Genetic aspects of monomorphic teratozoospermia: a review. Journal of assisted reproduction and genetics \n                           32, 615\u2013623, https:\/\/doi.org\/10.1007\/s10815-015-0433-2 (2015).","journal-title":"Journal of assisted reproduction and genetics"},{"key":"16005_CR15","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1007\/s00441-015-2320-7","volume":"363","author":"DT Carrell","year":"2016","unstructured":"Carrell, D. T., Aston, K. I., Oliva, R., Emery, B. R. & De Jonge, C. J. The \u201comics\u201d of human male infertility: integrating big data in a systems biology approach. Cell and tissue research \n                           363, 295\u2013312, https:\/\/doi.org\/10.1007\/s00441-015-2320-7 (2016).","journal-title":"Cell and tissue research"},{"key":"16005_CR16","doi-asserted-by":"publisher","first-page":"734","DOI":"10.1016\/S1472-6483(10)60677-3","volume":"14","author":"A Ferlin","year":"2007","unstructured":"Ferlin, A. et al. Male infertility: role of genetic background. Reproductive biomedicine online \n                           14, 734\u2013745 (2007).","journal-title":"Reproductive biomedicine online"},{"key":"16005_CR17","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-15-341","volume":"15","author":"G Rallapalli","year":"2014","unstructured":"Rallapalli, G. et al. EXPRSS: an Illumina based high-throughput expression-profiling method to reveal transcriptional dynamics. BMC genomics \n                           15, 341, https:\/\/doi.org\/10.1186\/1471-2164-15-341 (2014).","journal-title":"BMC genomics"},{"key":"16005_CR18","doi-asserted-by":"publisher","first-page":"1650","DOI":"10.1016\/j.fertnstert.2006.04.039","volume":"86","author":"YH Lin","year":"2006","unstructured":"Lin, Y. H. et al. Identification of ten novel genes involved in human spermatogenesis by microarray analysis of testicular tissue. Fertility and sterility \n                           86, 1650\u20131658, https:\/\/doi.org\/10.1016\/j.fertnstert.2006.04.039 (2006).","journal-title":"Fertility and sterility"},{"key":"16005_CR19","doi-asserted-by":"publisher","first-page":"e26","DOI":"10.1371\/journal.pgen.0040026","volume":"4","author":"H Okada","year":"2008","unstructured":"Okada, H. et al. Genome-wide expression of azoospermia testes demonstrates a specific profile and implicates ART3 in genetic susceptibility. PLoS genetics \n                           4, e26, https:\/\/doi.org\/10.1371\/journal.pgen.0040026 (2008).","journal-title":"PLoS genetics"},{"key":"16005_CR20","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-11-401","volume":"11","author":"V Gatta","year":"2010","unstructured":"Gatta, V. et al. Testis transcriptome analysis in male infertility: new insight on the pathogenesis of oligo-azoospermia in cases with and without AZFc microdeletion. BMC genomics \n                           11, 401, https:\/\/doi.org\/10.1186\/1471-2164-11-401 (2010).","journal-title":"BMC genomics"},{"key":"16005_CR21","doi-asserted-by":"publisher","first-page":"e15541","DOI":"10.1371\/journal.pone.0015541","volume":"5","author":"M Saito","year":"2010","unstructured":"Saito, M. et al. Targeted disruption of Ing2 results in defective spermatogenesis and development of soft-tissue sarcomas. PloS one \n                           5, e15541, https:\/\/doi.org\/10.1371\/journal.pone.0015541 (2010).","journal-title":"PloS one"},{"issue":"1686-1694","key":"16005_CR22","doi-asserted-by":"publisher","first-page":"e1681","DOI":"10.1016\/j.fertnstert.2013.07.1999","volume":"100","author":"A Malcher","year":"2013","unstructured":"Malcher, A. et al. Potential biomarkers of nonobstructive azoospermia identified in microarray gene expression analysis. Fertility and sterility \n                           100(1686\u20131694), e1681\u20131687, https:\/\/doi.org\/10.1016\/j.fertnstert.2013.07.1999 (2013).","journal-title":"Fertility and sterility"},{"key":"16005_CR23","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1111\/aji.12149","volume":"70","author":"A Malcher","year":"2013","unstructured":"Malcher, A. et al. The gene expression analysis of paracrine\/autocrine factors in patients with spermatogenetic failure compared with normal spermatogenesis. Am J Reprod Immunol \n                           70, 522\u2013528, https:\/\/doi.org\/10.1111\/aji.12149 (2013).","journal-title":"Am J Reprod Immunol"},{"key":"16005_CR24","doi-asserted-by":"publisher","first-page":"e0127007","DOI":"10.1371\/journal.pone.0127007","volume":"10","author":"SK Bansal","year":"2015","unstructured":"Bansal, S. K., Gupta, N., Sankhwar, S. N. & Rajender, S. Differential Genes Expression between Fertile and Infertile Spermatozoa Revealed by Transcriptome Analysis. PloS one \n                           10, e0127007, https:\/\/doi.org\/10.1371\/journal.pone.0127007 (2015).","journal-title":"PloS one"},{"key":"16005_CR25","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.1021\/acs.jproteome.5b01080","volume":"15","author":"N Ansari-Pour","year":"2016","unstructured":"Ansari-Pour, N., Razaghi-Moghadam, Z., Barneh, F. & Jafari, M. Testis-Specific Y-Centric Protein-Protein Interaction Network Provides Clues to the Etiology of Severe Spermatogenic Failure. Journal of proteome research \n                           15, 1011\u20131022, https:\/\/doi.org\/10.1021\/acs.jproteome.5b01080 (2016).","journal-title":"Journal of proteome research"},{"key":"16005_CR26","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-15-515","volume":"15","author":"MM Croken","year":"2014","unstructured":"Croken, M. M., Qiu, W., White, M. W. & Kim, K. Gene Set Enrichment Analysis (GSEA) of Toxoplasma gondii expression datasets links cell cycle progression and the bradyzoite developmental program. BMC genomics \n                           15, 515, https:\/\/doi.org\/10.1186\/1471-2164-15-515 (2014).","journal-title":"BMC genomics"},{"key":"16005_CR27","doi-asserted-by":"publisher","first-page":"R47","DOI":"10.1530\/EJE-15-0080","volume":"173","author":"E Nieschlag","year":"2015","unstructured":"Nieschlag, E. & Vorona, E. MECHANISMS IN ENDOCRINOLOGY: Medical consequences of doping with anabolic androgenic steroids: effects on reproductive functions. European journal of endocrinology \n                           173, R47\u201358, https:\/\/doi.org\/10.1530\/EJE-15-0080 (2015).","journal-title":"European journal of endocrinology"},{"key":"16005_CR28","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1016\/j.contraception.2010.03.020","volume":"82","author":"E Nieschlag","year":"2010","unstructured":"Nieschlag, E. Clinical trials in male hormonal contraception. Contraception \n                           82, 457\u2013470, https:\/\/doi.org\/10.1016\/j.contraception.2010.03.020 (2010).","journal-title":"Contraception"},{"key":"16005_CR29","doi-asserted-by":"publisher","first-page":"1891","DOI":"10.1096\/fj.13-245480","volume":"28","author":"K Sato","year":"2014","unstructured":"Sato, K. et al. Resistance training restores muscle sex steroid hormone steroidogenesis in older men. FASEB journal: official publication of the Federation of American Societies for Experimental Biology \n                           28, 1891\u20131897, https:\/\/doi.org\/10.1096\/fj.13-245480 (2014).","journal-title":"FASEB journal: official publication of the Federation of American Societies for Experimental Biology"},{"key":"16005_CR30","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1038\/nature08195","volume":"460","author":"KR Cordes","year":"2009","unstructured":"Cordes, K. R. et al. miR-145 and miR-143 regulate smooth muscle cell fate and plasticity. Nature \n                           460, 705\u2013710, https:\/\/doi.org\/10.1038\/nature08195 (2009).","journal-title":"Nature"},{"key":"16005_CR31","doi-asserted-by":"publisher","first-page":"6569","DOI":"10.1038\/onc.2010.386","volume":"29","author":"M Gotte","year":"2010","unstructured":"Gotte, M. et al. miR-145-dependent targeting of junctional adhesion molecule A and modulation of fascin expression are associated with reduced breast cancer cell motility and invasiveness. Oncogene \n                           29, 6569\u20136580, https:\/\/doi.org\/10.1038\/onc.2010.386 (2010).","journal-title":"Oncogene"},{"key":"16005_CR32","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1111\/and.12484","volume":"48","author":"G Fu","year":"2016","unstructured":"Fu, G., Wei, Y., Wang, X. & Yu, L. Identification of candidate causal genes and their associated pathogenic mechanisms underlying teratozoospermia based on the spermatozoa transcript profiles. Andrologia \n                           48, 576\u2013583, https:\/\/doi.org\/10.1111\/and.12484 (2016).","journal-title":"Andrologia"},{"key":"16005_CR33","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1111\/j.1439-0272.1999.tb02848.x","volume":"31","author":"M Szczygiel","year":"1999","unstructured":"Szczygiel, M. & Kurpisz, M. Teratozoospermia and its effect on male fertility potential. Andrologia \n                           31, 63\u201375 (1999).","journal-title":"Andrologia"},{"key":"16005_CR34","doi-asserted-by":"publisher","first-page":"481","DOI":"10.4103\/1008-682X.143737","volume":"17","author":"DK Xiong","year":"2015","unstructured":"Xiong, D. K., Chen, H. H., Ding, X. P., Zhang, S. H. & Zhang, J. H. Association of polymorphisms in glutathione S-transferase genes (GSTM1, GSTT1, GSTP1) with idiopathic azoospermia or oligospermia in Sichuan, China. Asian journal of andrology \n                           17, 481\u2013486, https:\/\/doi.org\/10.4103\/1008-682X.143737 (2015).","journal-title":"Asian journal of andrology"},{"key":"16005_CR35","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2490-12-6","volume":"12","author":"F Atig","year":"2012","unstructured":"Atig, F. et al. Impact of seminal trace element and glutathione levels on semen quality of Tunisian infertile men. BMC urology \n                           12, 6, https:\/\/doi.org\/10.1186\/1471-2490-12-6 (2012).","journal-title":"BMC urology"},{"key":"16005_CR36","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1111\/j.1745-7262.2008.00347.x","volume":"10","author":"QF Wu","year":"2008","unstructured":"Wu, Q. F. et al. Genetic polymorphism of glutathione S-transferase T1 gene and susceptibility to idiopathic azoospermia or oligospermia in northwestern China. Asian journal of andrology \n                           10, 266\u2013270, https:\/\/doi.org\/10.1111\/j.1745-7262.2008.00347.x (2008).","journal-title":"Asian journal of andrology"},{"key":"16005_CR37","first-page":"225","volume":"2","author":"A Bhardwaj","year":"2000","unstructured":"Bhardwaj, A., Verma, A., Majumdar, S. & Khanduja, K. L. Status of vitamin E and reduced glutathione in semen of oligozoospermic and azoospermic patients. Asian journal of andrology \n                           2, 225\u2013228 (2000).","journal-title":"Asian journal of andrology"},{"key":"16005_CR38","doi-asserted-by":"publisher","DOI":"10.1186\/s12014-015-9094-5","volume":"12","author":"A Agarwal","year":"2015","unstructured":"Agarwal, A. et al. Comparative proteomic network signatures in seminal plasma of infertile men as a function of reactive oxygen species. Clinical proteomics \n                           12, 23, https:\/\/doi.org\/10.1186\/s12014-015-9094-5 (2015).","journal-title":"Clinical proteomics"},{"key":"16005_CR39","doi-asserted-by":"publisher","first-page":"529271","DOI":"10.1155\/2014\/529271","volume":"2014","author":"H Hu","year":"2014","unstructured":"Hu, H. et al. RNA-Seq identifies key reproductive gene expression alterations in response to cadmium exposure. BioMed research international \n                           2014, 529271, https:\/\/doi.org\/10.1155\/2014\/529271 (2014).","journal-title":"BioMed research international"},{"key":"16005_CR40","doi-asserted-by":"publisher","first-page":"206","DOI":"10.3109\/19396368.2014.918675","volume":"60","author":"A Agarwal","year":"2014","unstructured":"Agarwal, A., Mulgund, A., Sharma, R. & Sabanegh, E. Mechanisms of oligozoospermia: an oxidative stress perspective. Systems biology in reproductive medicine \n                           60, 206\u2013216, https:\/\/doi.org\/10.3109\/19396368.2014.918675 (2014).","journal-title":"Systems biology in reproductive medicine"},{"key":"16005_CR41","doi-asserted-by":"publisher","first-page":"1447","DOI":"10.1016\/j.fertnstert.2004.11.062","volume":"83","author":"MR Hussein","year":"2005","unstructured":"Hussein, M. R. et al. Phenotypic characterization of the immune and mast cell infiltrates in the human testis shows normal and abnormal spermatogenesis. Fertility and sterility \n                           83, 1447\u20131453, https:\/\/doi.org\/10.1016\/j.fertnstert.2004.11.062 (2005).","journal-title":"Fertility and sterility"},{"key":"16005_CR42","doi-asserted-by":"publisher","first-page":"1020","DOI":"10.1111\/andr.12246","volume":"4","author":"P Noveski","year":"2016","unstructured":"Noveski, P. et al. MicroRNA expression profiles in testicular biopsies of patients with impaired spermatogenesis. Andrology \n                           4, 1020\u20131027, https:\/\/doi.org\/10.1111\/andr.12246 (2016).","journal-title":"Andrology"},{"key":"16005_CR43","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/1477-7827-7-13","volume":"7","author":"J Lian","year":"2009","unstructured":"Lian, J. et al. Altered microRNA expression in patients with non-obstructive azoospermia. Reproductive biology and endocrinology: RB&E \n                           7, 13, https:\/\/doi.org\/10.1186\/1477-7827-7-13 (2009).","journal-title":"Reproductive biology and endocrinology: RB&E"},{"key":"16005_CR44","doi-asserted-by":"publisher","first-page":"4365","DOI":"10.3892\/mmr.2015.3273","volume":"11","author":"L Zhang","year":"2015","unstructured":"Zhang, L. et al. Association of hsa-miR145 overexpression in human testicular cells with male infertility. Molecular medicine reports \n                           11, 4365\u20134372, https:\/\/doi.org\/10.3892\/mmr.2015.3273 (2015).","journal-title":"Molecular medicine reports"},{"key":"16005_CR45","doi-asserted-by":"publisher","first-page":"810","DOI":"10.1006\/bbrc.1999.1322","volume":"263","author":"DP Cerretti","year":"1999","unstructured":"Cerretti, D. P., DuBose, R. F., Black, R. A. & Nelson, N. Isolation of two novel metalloproteinase-disintegrin (ADAM) cDNAs that show testis-specific gene expression. Biochemical and biophysical research communications \n                           263, 810\u2013815, https:\/\/doi.org\/10.1006\/bbrc.1999.1322 (1999).","journal-title":"Biochemical and biophysical research communications"},{"key":"16005_CR46","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/S0378-1119(97)00417-4","volume":"200","author":"J Neesen","year":"1997","unstructured":"Neesen, J. et al. Identification of dynein heavy chain genes expressed in human and mouse testis: chromosomal localization of an axonemal dynein gene. Gene \n                           200, 193\u2013202 (1997).","journal-title":"Gene"},{"key":"16005_CR47","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1002\/pmic.201300225","volume":"14","author":"S Wang","year":"2014","unstructured":"Wang, S. et al. Proteomic characteristics of human sperm cryopreservation. Proteomics \n                           14, 298\u2013310, https:\/\/doi.org\/10.1002\/pmic.201300225 (2014).","journal-title":"Proteomics"},{"key":"16005_CR48","doi-asserted-by":"publisher","first-page":"2081","DOI":"10.1101\/gad.1951010","volume":"24","author":"Y Wang","year":"2010","unstructured":"Wang, Y., Stary, J. M., Wilhelm, J. E. & Newmark, P. A. A functional genomic screen in planarians identifies novel regulators of germ cell development. Genes & development \n                           24, 2081\u20132092, https:\/\/doi.org\/10.1101\/gad.1951010 (2010).","journal-title":"Genes & development"},{"key":"16005_CR49","doi-asserted-by":"publisher","first-page":"824","DOI":"10.1038\/aja.2013.93","volume":"15","author":"J Wei","year":"2013","unstructured":"Wei, J. et al. Characterisation of Lyzls in mice and antibacterial properties of human LYZL6. Asian journal of andrology \n                           15, 824\u2013830, https:\/\/doi.org\/10.1038\/aja.2013.93 (2013).","journal-title":"Asian journal of andrology"},{"key":"16005_CR50","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1530\/REP-14-0394","volume":"149","author":"DL Cullinane","year":"2015","unstructured":"Cullinane, D. L., Chowdhury, T. A. & Kleene, K. C. Mechanisms of translational repression of the Smcp mRNA in round spermatids. Reproduction \n                           149, 43\u201354, https:\/\/doi.org\/10.1530\/REP-14-0394 (2015).","journal-title":"Reproduction"},{"key":"16005_CR51","doi-asserted-by":"publisher","first-page":"16289","DOI":"10.1074\/jbc.M211023200","volume":"278","author":"B Lu","year":"2003","unstructured":"Lu, B. & Bishop, C. E. Mouse GGN1 and GGN3, two germ cell-specific proteins from the single gene Ggn, interact with mouse POG and play a role in spermatogenesis. The Journal of biological chemistry \n                           278, 16289\u201316296, https:\/\/doi.org\/10.1074\/jbc.M211023200 (2003).","journal-title":"The Journal of biological chemistry"},{"key":"16005_CR52","doi-asserted-by":"publisher","first-page":"11131","DOI":"10.1073\/pnas.0812789106","volume":"106","author":"P Grimaldi","year":"2009","unstructured":"Grimaldi, P. et al. The endocannabinoid system and pivotal role of the CB2 receptor in mouse spermatogenesis. Proceedings of the National Academy of Sciences of the United States of America \n                           106, 11131\u201311136, https:\/\/doi.org\/10.1073\/pnas.0812789106 (2009).","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"16005_CR53","doi-asserted-by":"publisher","first-page":"1200","DOI":"10.1002\/pmic.201200489","volume":"13","author":"M Liu","year":"2013","unstructured":"Liu, M. et al. Scanning of novel cancer\/testis proteins by human testis proteomic analysis. Proteomics \n                           13, 1200\u20131210, https:\/\/doi.org\/10.1002\/pmic.201200489 (2013).","journal-title":"Proteomics"},{"key":"16005_CR54","doi-asserted-by":"publisher","DOI":"10.1038\/srep07922","volume":"5","author":"X Zhuang","year":"2015","unstructured":"Zhuang, X. et al. Integrated miRNA and mRNA expression profiling to identify mRNA targets of dysregulated miRNAs in non-obstructive azoospermia. Scientific reports \n                           5, 7922, https:\/\/doi.org\/10.1038\/srep07922 (2015).","journal-title":"Scientific reports"},{"key":"16005_CR55","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1089\/104454901317094990","volume":"20","author":"MP Cuajungco","year":"2001","unstructured":"Cuajungco, M. P. et al. Cloning, characterization, and genomic structure of the mouse Ikbkap gene. DNA and cell biology \n                           20, 579\u2013586, https:\/\/doi.org\/10.1089\/104454901317094990 (2001).","journal-title":"DNA and cell biology"},{"key":"16005_CR56","doi-asserted-by":"publisher","first-page":"5132","DOI":"10.1158\/1078-0432.CCR-11-0072","volume":"17","author":"S Modi","year":"2011","unstructured":"Modi, S. et al. HSP90 inhibition is effective in breast cancer: a phase II trial of tanespimycin (17-AAG) plus trastuzumab in patients with HER2-positive metastatic breast cancer progressing on trastuzumab. Clinical cancer research: an official journal of the American Association for Cancer Research \n                           17, 5132\u20135139, https:\/\/doi.org\/10.1158\/1078-0432.CCR-11-0072 (2011).","journal-title":"Clinical cancer research: an official journal of the American Association for Cancer Research"},{"key":"16005_CR57","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1093\/nar\/30.1.207","volume":"30","author":"R Edgar","year":"2002","unstructured":"Edgar, R., Domrachev, M. & Lash, A. E. Gene Expression Omnibus: NCBI gene expression and hybridization array data repository. Nucleic acids research \n                           30, 207\u2013210 (2002).","journal-title":"Nucleic acids research"},{"key":"16005_CR58","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-14-128","volume":"14","author":"EY Chen","year":"2013","unstructured":"Chen, E. Y. et al. Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool. BMC bioinformatics \n                           14, 128, https:\/\/doi.org\/10.1186\/1471-2105-14-128 (2013).","journal-title":"BMC bioinformatics"},{"key":"16005_CR59","doi-asserted-by":"publisher","first-page":"20130950","DOI":"10.1098\/rsif.2013.0950","volume":"11","author":"G Hong","year":"2014","unstructured":"Hong, G., Zhang, W., Li, H., Shen, X. & Guo, Z. Separate enrichment analysis of pathways for up- and downregulated genes. Journal of the Royal Society, Interface \n                           11, 20130950, https:\/\/doi.org\/10.1098\/rsif.2013.0950 (2014).","journal-title":"Journal of the Royal Society, Interface"},{"key":"16005_CR60","doi-asserted-by":"publisher","first-page":"e1002347","DOI":"10.1371\/journal.pcbi.1002347","volume":"8","author":"D Shigemizu","year":"2012","unstructured":"Shigemizu, D. et al. Using functional signatures to identify repositioned drugs for breast, myelogenous leukemia and prostate cancer. PLoS computational biology \n                           8, e1002347, https:\/\/doi.org\/10.1371\/journal.pcbi.1002347 (2012).","journal-title":"PLoS computational biology"},{"key":"16005_CR61","doi-asserted-by":"publisher","first-page":"W84","DOI":"10.1093\/nar\/gkt516","volume":"41","author":"D D\u2019Andrea","year":"2013","unstructured":"D\u2019Andrea, D., Grassi, L., Mazzapioda, M. & Tramontano, A. FIDEA: a server for the functional interpretation of differential expression analysis. Nucleic acids research \n                           41, W84\u201388, https:\/\/doi.org\/10.1093\/nar\/gkt516 (2013).","journal-title":"Nucleic acids research"},{"key":"16005_CR62","doi-asserted-by":"publisher","DOI":"10.1038\/srep33262","volume":"6","author":"C Feng","year":"2016","unstructured":"Feng, C. et al. Subpathway-CorSP: Identification of metabolic subpathways via integrating expression correlations and topological features between metabolites and genes of interest within pathways. Scientific reports \n                           6, 33262, https:\/\/doi.org\/10.1038\/srep33262 (2016).","journal-title":"Scientific reports"},{"key":"16005_CR63","doi-asserted-by":"publisher","DOI":"10.1038\/srep35322","volume":"6","author":"U Golla","year":"2016","unstructured":"Golla, U., Joseph, D. & Tomar, R. S. Combined Transcriptomics and Chemical-Genetics Reveal Molecular Mode of Action of Valproic acid, an Anticancer Molecule using Budding Yeast Model. Scientific reports \n                           6, 35322, https:\/\/doi.org\/10.1038\/srep35322 (2016).","journal-title":"Scientific reports"},{"key":"16005_CR64","doi-asserted-by":"publisher","DOI":"10.1038\/srep24869","volume":"6","author":"M Li","year":"2016","unstructured":"Li, M. et al. Identifying Reproducible Molecular Biomarkers for Gastric Cancer Metastasis with the Aid of Recurrence Information. Scientific reports \n                           6, 24869, https:\/\/doi.org\/10.1038\/srep24869 (2016).","journal-title":"Scientific reports"},{"key":"16005_CR65","doi-asserted-by":"publisher","first-page":"1831","DOI":"10.1634\/stemcells.2007-1033","volume":"26","author":"J Synnergren","year":"2008","unstructured":"Synnergren, J. et al. Molecular signature of cardiomyocyte clusters derived from human embryonic stem cells. Stem Cells \n                           26, 1831\u20131840, https:\/\/doi.org\/10.1634\/stemcells.2007-1033 (2008).","journal-title":"Stem Cells"},{"issue":"2904","key":"16005_CR66","doi-asserted-by":"publisher","first-page":"e2901","DOI":"10.1016\/j.neurobiolaging.2015.06.006","volume":"36","author":"X Bao","year":"2015","unstructured":"Bao, X. et al. Cell adhesion molecule pathway genes are regulated by cis-regulatory SNPs and show significantly altered expression in Alzheimer\u2019s disease brains. Neurobiology of aging \n                           36(2904), e2901\u20132907, https:\/\/doi.org\/10.1016\/j.neurobiolaging.2015.06.006 (2015).","journal-title":"Neurobiology of aging"},{"key":"16005_CR67","doi-asserted-by":"publisher","first-page":"e0170441","DOI":"10.1371\/journal.pone.0170441","volume":"12","author":"L Stenz","year":"2017","unstructured":"Stenz, L., Escoffier, J., Rahban, R., Nef, S. & Paoloni-Giacobino, A. Testicular Dysgenesis Syndrome and Long-Lasting Epigenetic Silencing of Mouse Sperm Genes Involved in the Reproductive System after Prenatal Exposure to DEHP. PloS one \n                           12, e0170441, https:\/\/doi.org\/10.1371\/journal.pone.0170441 (2017).","journal-title":"PloS one"},{"key":"16005_CR68","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1007\/s12079-017-0387-5","volume":"11","author":"M Talkhabi","year":"2017","unstructured":"Talkhabi, M., Razavi, S. M. & Salari, A. Global transcriptomic analysis of induced cardiomyocytes predicts novel regulators for direct cardiac reprogramming. Journal of cell communication and signaling \n                           11, 193\u2013204, https:\/\/doi.org\/10.1007\/s12079-017-0387-5 (2017).","journal-title":"Journal of cell communication and signaling"},{"key":"16005_CR69","doi-asserted-by":"publisher","first-page":"15545","DOI":"10.1073\/pnas.0506580102","volume":"102","author":"A Subramanian","year":"2005","unstructured":"Subramanian, A. et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proceedings of the National Academy of Sciences of the United States of America \n                           102, 15545\u201315550, https:\/\/doi.org\/10.1073\/pnas.0506580102 (2005).","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"16005_CR70","doi-asserted-by":"publisher","first-page":"20150202","DOI":"10.1098\/rsta.2015.0202","volume":"374","author":"IT Jolliffe","year":"2016","unstructured":"Jolliffe, I. T. & Cadima, J. Principal component analysis: a review and recent developments. Philosophical transactions. Series A, Mathematical, physical, and engineering sciences \n                           374, 20150202, https:\/\/doi.org\/10.1098\/rsta.2015.0202 (2016).","journal-title":"Series A, Mathematical, physical, and engineering sciences"},{"key":"16005_CR71","doi-asserted-by":"publisher","first-page":"e20280","DOI":"10.1371\/journal.pone.0020280","volume":"6","author":"SE Pacheco","year":"2011","unstructured":"Pacheco, S. E. et al. Integrative DNA methylation and gene expression analyses identify DNA packaging and epigenetic regulatory genes associated with low motility sperm. PloS one \n                           6, e20280, https:\/\/doi.org\/10.1371\/journal.pone.0020280 (2011).","journal-title":"PloS one"},{"key":"16005_CR72","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1093\/hmg\/ddm012","volume":"16","author":"AE Platts","year":"2007","unstructured":"Platts, A. E. et al. Success and failure in human spermatogenesis as revealed by teratozoospermic RNAs. Human molecular genetics \n                           16, 763\u2013773, https:\/\/doi.org\/10.1093\/hmg\/ddm012 (2007).","journal-title":"Human molecular genetics"},{"key":"16005_CR73","doi-asserted-by":"publisher","first-page":"1114","DOI":"10.1095\/biolreprod.111.091793","volume":"85","author":"X Wu","year":"2011","unstructured":"Wu, X., Goodyear, S. M., Tobias, J. W., Avarbock, M. R. & Brinster, R. L. Spermatogonial stem cell self-renewal requires ETV5-mediated downstream activation of Brachyury in mice. Biology of reproduction \n                           85, 1114\u20131123, https:\/\/doi.org\/10.1095\/biolreprod.111.091793 (2011).","journal-title":"Biology of reproduction"},{"key":"16005_CR74","doi-asserted-by":"publisher","first-page":"9858","DOI":"10.1093\/nar\/gkt746","volume":"41","author":"HY Chen","year":"2013","unstructured":"Chen, H. Y., Yu, Y. H. & Yen, P. H. DAZAP1 regulates the splicing of Crem, Crisp2 and Pot1a transcripts. Nucleic acids research \n                           41, 9858\u20139869, https:\/\/doi.org\/10.1093\/nar\/gkt746 (2013).","journal-title":"Nucleic acids research"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-16005-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-16005-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-16005-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T13:43:59Z","timestamp":1671803039000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-16005-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,11,17]]},"references-count":74,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["16005"],"URL":"https:\/\/doi.org\/10.1038\/s41598-017-16005-0","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,11,17]]},"assertion":[{"value":"19 April 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 November 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 November 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"15778"}}