{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T15:28:02Z","timestamp":1790782082132,"version":"4.1.0"},"reference-count":109,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,4,16]],"date-time":"2020-04-16T00:00:00Z","timestamp":1586995200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R03 HD098314"],"award-info":[{"award-number":["R03 HD098314"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R21 HD092700"],"award-info":[{"award-number":["R21 HD092700"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Infertility is a devastating experience for both partners as they try to conceive. Historically, when a couple could not conceive, the woman has carried the stigma of infertility; however, men and women are just as likely to contribute to the couple\u2019s infertility. With the development of assisted reproductive technology (ART), the treatment burden for male and unexplained infertility has fallen mainly on women. Equalizing this burden requires reviving research on male infertility to both improve treatment options and enable natural conception. Despite many scientific efforts, infertility in men due to sperm dysfunction is mainly diagnosed by a semen analysis. The semen analysis is limited as it only examines general sperm properties such as concentration, motility, and morphology. A diagnosis of male infertility rarely includes an assessment of internal sperm components such as DNA, which is well documented to have an impact on infertility, or other components such as RNA and centrioles, which are beginning to be adopted. Assessment of these components is not typically included in current diagnostic testing because available treatments are limited. Recent research has expanded our understanding of sperm biology and suggests that these components may also contribute to the failure to achieve pregnancy. Understanding the sperm\u2019s internal components, and how they contribute to male infertility, would provide avenues for new therapies that are based on treating men directly for male infertility, which may enable less invasive treatments and even natural conception.<\/jats:p>","DOI":"10.3390\/cells9040990","type":"journal-article","created":{"date-parts":[[2020,4,16]],"date-time":"2020-04-16T13:01:39Z","timestamp":1587042099000},"page":"990","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":105,"title":["Male Infertility is a Women\u2019s Health Issue\u2014Research and Clinical Evaluation of Male Infertility Is Needed"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9530-6595","authenticated-orcid":false,"given":"Katerina A.","family":"Turner","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, University of Toledo, Toledo, OH 43606, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amarnath","family":"Rambhatla","sequence":"additional","affiliation":[{"name":"Department of Urology, Vattikuti Urology Institute, Henry Ford Health System, Detroit, MI 48202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Schon","sequence":"additional","affiliation":[{"name":"Division of Reproductive Endocrinology &amp; Infertility, Department of Obstetrics and Gynecology, University of Michigan Medical School, L4000 UH-South, 1500 E. Medical Center Drive, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0585-1026","authenticated-orcid":false,"given":"Ashok","family":"Agarwal","sequence":"additional","affiliation":[{"name":"American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen A.","family":"Krawetz","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Center for Molecular Medicine and Genetics, C.S. Mott Center for Human Growth and Development, Wayne State University School of Medicine, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4290-9648","authenticated-orcid":false,"given":"James M.","family":"Dupree","sequence":"additional","affiliation":[{"name":"Department of Urology and Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI 48019, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0918-526X","authenticated-orcid":false,"given":"Tomer","family":"Avidor-Reiss","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Toledo, Toledo, OH 43606, USA"},{"name":"Department of Urology, College of Medicine and Life Sciences, University of Toledo, Toledo, OH 43614, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,16]]},"reference":[{"key":"ref_1","first-page":"287","article-title":"Not every sperm is sacred; a perspective on male infertility","volume":"24","author":"Aitken","year":"2018","journal-title":"Mol. Hum. Reprod."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1093\/humupd\/dmu042","article-title":"Ultrasound of the male genital tract in relation to male reproductive health","volume":"21","author":"Lotti","year":"2015","journal-title":"Hum. Reprod. Update"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"426","DOI":"10.4103\/1008-682X.175781","article-title":"Seminal biomarkers for the evaluation of male infertility","volume":"18","author":"Bieniek","year":"2016","journal-title":"Asian J. Androl."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.jprot.2016.08.018","article-title":"Semen proteomics and male infertility","volume":"162","author":"Jodar","year":"2017","journal-title":"J. Proteom."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1111\/j.1365-2605.2004.00502.x","article-title":"Hormonal regulation of spermatogenesis","volume":"27","author":"Holdcraft","year":"2004","journal-title":"Int. J. Androl."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1007\/s00345-003-0365-9","article-title":"Androgens and male fertility","volume":"21","author":"Dohle","year":"2003","journal-title":"World J. Urol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2681","DOI":"10.1007\/s00018-019-03101-9","article-title":"The roles and mechanisms of Leydig cells and myoid cells in regulating spermatogenesis","volume":"76","author":"Zhou","year":"2019","journal-title":"Cell Mol. Life Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1007\/s00441-017-2667-z","article-title":"MicroRNAs in Sertoli cells: Implications for spermatogenesis and fertility","volume":"370","author":"Costa","year":"2017","journal-title":"Cell Tissue Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1080\/14737159.2018.1453358","article-title":"Testing for genetic contributions to infertility: Potential clinical impact","volume":"18","author":"Krausz","year":"2018","journal-title":"Expert Rev. Mol. Diagn."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1038\/nrurol.2018.20","article-title":"Sexual dysfunction and male infertility","volume":"15","author":"Lotti","year":"2018","journal-title":"Nat. Rev. Urol."},{"key":"ref_11","unstructured":"Chandra, A., Copen, C.E., and Stephen, E.H. (2013). Infertility and impaired fecundity in the United States, 1982-2010: Data from the National Survey of Family Growth. Natl. Health Stat. Rep., 1\u201318. 11 p following 19."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1016\/j.fertnstert.2019.04.044","article-title":"Disparities in accessing infertility care in the United States: Results from the National Health and Nutrition Examination Survey, 2013-16","volume":"112","author":"Kelley","year":"2019","journal-title":"Fertil. Steril."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1016\/S1472-6483(10)61082-6","article-title":"Medical treatment to improve sperm quality","volume":"12","author":"Isidori","year":"2006","journal-title":"Reprod. Biomed. Online"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1093\/oxfordjournals.humrep.a137433","article-title":"Incidence and main causes of infertility in a resident population (1 850 000) of three French regions (1988\u20131989)*","volume":"6","author":"Thonneau","year":"1991","journal-title":"Hum. Reprod."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/S1521-6934(02)00146-3","article-title":"Subfertility: Causes, treatment and outcome","volume":"17","author":"Adamson","year":"2003","journal-title":"Best Pract. Res. Clin. Obs. Gynaecol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1093\/humrep\/deh870","article-title":"Definition and prevalence of subfertility and infertility","volume":"20","author":"Gnoth","year":"2005","journal-title":"Hum. Reprod."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1016\/j.fertnstert.2015.01.029","article-title":"Fluorescence in situ hybridization detects increased sperm aneuploidy in men with recurrent pregnancy loss","volume":"103","author":"Ramasamy","year":"2015","journal-title":"Fertil. Steril."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s12610-018-0070-6","article-title":"Sperm aneuploidy and DNA fragmentation in unexplained recurrent pregnancy loss: A multicenter case-control study","volume":"28","author":"Walschaerts","year":"2018","journal-title":"Basic Clin."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4","DOI":"10.21037\/amj.2019.01.01","article-title":"Practice Patterns for the Treatment of Idiopathic Infertility: Is There a Role for Advanced Semen Testing?","volume":"4","author":"Patel","year":"2019","journal-title":"AME Med. J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s12958-015-0032-1","article-title":"A unique view on male infertility around the globe","volume":"13","author":"Agarwal","year":"2015","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_21","first-page":"42","article-title":"Gender differences in psychological reactions to infertility among couples seeking IVF-and ICSI-treatment","volume":"78","author":"Hjelmstedt","year":"1999","journal-title":"Acta Obstet. Gynecol. Scand."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"(2015). Diagnostic evaluation of the infertile female: A committee opinion. Fertil. Steril., 103, e44\u2013e50.","DOI":"10.1016\/j.fertnstert.2015.03.019"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1001\/jama.281.6.537","article-title":"Sexual dysfunction in the United States: Prevalence and predictors","volume":"281","author":"Laumann","year":"1999","journal-title":"JAMA"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2665","DOI":"10.1093\/humrep\/dew241","article-title":"IUI and IVF for unexplained subfertility: Where did we go wrong?","volume":"31","author":"Bensdorp","year":"2016","journal-title":"Hum. Reprod."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"70","DOI":"10.4103\/0974-1208.86080","article-title":"Ovarian hyperstimulation syndrome","volume":"4","author":"Kumar","year":"2011","journal-title":"J. Hum. Reprod. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1080\/19396368.2017.1382608","article-title":"Donor sperm insemination after failed intra-couple intracytoplasmic sperm injection","volume":"64","author":"Hennebicq","year":"2018","journal-title":"Syst. Biol. Reprod. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/0140-6736(92)92425-F","article-title":"Pregnancies after intracytoplasmic injection of single spermatozoon into an oocyte","volume":"340","author":"Palermo","year":"1992","journal-title":"Lancet"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/humrep\/der447","article-title":"Celebrating ICSI\u2019s twentieth anniversary and the birth of more than 2.5 million children\u2014The \u2018how, why, when and where\u2019","volume":"27","year":"2012","journal-title":"Hum. Reprod."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1093\/humrep\/dey020","article-title":"\u2018Man Up\u2019: The importance and strategy for placing male reproductive health centre stage in the political and research agenda","volume":"33","author":"Barratt","year":"2018","journal-title":"Hum. Reprod. (Oxf. Engl.)"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Marzano, G., Chiriaco, M.S., Primiceri, E., Dell\u2019Aquila, M.E., Ramalho-Santos, J., Zara, V., Ferramosca, A., and Maruccio, G. (2019). Sperm selection in assisted reproduction: A review of established methods and cutting-edge possibilities. Biotechnol. Adv., 107498.","DOI":"10.1016\/j.biotechadv.2019.107498"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/S1701-2163(16)32112-0","article-title":"Pregnancy outcomes after assisted reproductive technology","volume":"28","author":"Allen","year":"2006","journal-title":"J. Obs. Gynaecol. Can."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1186\/s12958-018-0390-6","article-title":"Influencing factors of pregnancy loss and survival probability of clinical pregnancies conceived through assisted reproductive technology","volume":"16","author":"Hu","year":"2018","journal-title":"Reprod. Biol. Endocrinol. RBE"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1002\/bdr2.1055","article-title":"Assisted Reproductive Technology and Birth Defects: Effects of Subfertility and Multiple Births","volume":"109","author":"Liberman","year":"2017","journal-title":"Birth Defects Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1016\/j.fertnstert.2018.06.039","article-title":"International Committee for Monitoring Assisted Reproductive Technology: World report on assisted reproductive technology, 2011","volume":"110","author":"Adamson","year":"2018","journal-title":"Fertil. Steril."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1016\/j.fertnstert.2010.11.026","article-title":"Costs of infertility treatment: Results from an 18-month prospective cohort study","volume":"95","author":"Katz","year":"2011","journal-title":"Fertil. Steril."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1111\/1471-0528.15668","article-title":"Risk of severe maternal morbidity associated with in vitro fertilisation: A population-based study","volume":"126","author":"Pelage","year":"2019","journal-title":"BJOG"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1016\/j.fertnstert.2016.03.023","article-title":"Limitations and barriers in access to care for male factor infertility","volume":"105","author":"Mehta","year":"2016","journal-title":"Fertil. Steril."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/j.fertnstert.2009.02.012","article-title":"Distribution of male infertility specialists in relation to the male population and assisted reproductive technology centers in the United States","volume":"94","author":"Nangia","year":"2010","journal-title":"Fertil. Steril."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1093\/humrep\/deh269","article-title":"Clinical andrology\u2014still a major problem in the treatment of infertility","volume":"19","author":"Jequier","year":"2004","journal-title":"Hum. Reprod."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1111\/j.1610-0387.2007.06526.x","article-title":"Andrology","volume":"5","author":"Glander","year":"2007","journal-title":"JDDG: J. Dtsch. Dermatol. Ges."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"De Jonge, C., and Barratt, C.L.R. (2019). The present crisis in male reproductive health: An urgent need for a political, social, and research roadmap. Andrology, 7.","DOI":"10.1111\/andr.12673"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e27","DOI":"10.1016\/j.fertnstert.2018.07.093","article-title":"Total motile sperm count trend over time across two continents: Evaluation of semen analyses from 119,972 infertile men","volume":"110","author":"Tiegs","year":"2018","journal-title":"Fertil. Steril."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.1016\/S0140-6736(19)30690-7","article-title":"Populations, decreasing fertility, and reproductive health","volume":"393","author":"Skakkebaek","year":"2019","journal-title":"Lancet"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1093\/humupd\/dmx022","article-title":"Temporal trends in sperm count: A systematic review and meta-regression analysis","volume":"23","author":"Levine","year":"2017","journal-title":"Hum. Reprod. Update"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1016\/j.juro.2012.08.239","article-title":"Frequency of the Male Infertility Evaluation: Data from the National Survey of Family Growth","volume":"189","year":"2013","journal-title":"J. Urol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/S1472-6483(10)60442-7","article-title":"Demographics of infertility","volume":"18","author":"Ledger","year":"2009","journal-title":"Reprod. Biomed. Online"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/S1701-2163(15)30312-1","article-title":"An integrated approach to male-factor subfertility: Bridging the gap between fertility specialists trained in urology and gynaecology","volume":"37","author":"Hughes","year":"2015","journal-title":"J. Obs. Gynaecol. Can."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2807","DOI":"10.1093\/oxfordjournals.humrep.a019217","article-title":"Infertile male patients are patients, not numbers","volume":"11","author":"Canale","year":"1996","journal-title":"Hum. Reprod."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.bpobgyn.2006.12.003","article-title":"Psychological impact of infertility","volume":"21","author":"Cousineau","year":"2007","journal-title":"Best Pract. Res. Clin. Obstet. Gynaecol."},{"key":"ref_50","first-page":"131","article-title":"The emotional-psychological consequences of infertility among infertile women seeking treatment: Results of a qualitative study","volume":"12","author":"Simbar","year":"2014","journal-title":"Iran. J. Reprod. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1177\/1097184X02238525","article-title":"\u201cThe Worms Are Weak\u201d: Male Infertility and Patriarchal Paradoxes in Egypt","volume":"5","author":"Inhorn","year":"2003","journal-title":"Men Masc."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1111\/andr.12160","article-title":"Male infertility: An obstacle to sexuality?","volume":"4","author":"Bechoua","year":"2016","journal-title":"Andrology"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e1204499","DOI":"10.1080\/19420889.2016.1204499","article-title":"Why so many sperm cells? Not only a possible means of mitigating the hazards inherent to human reproduction but also an indicator of an exaptation","volume":"9","author":"Barlow","year":"2016","journal-title":"Commun. Integr. Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e1017156","DOI":"10.1080\/19420889.2015.1017156","article-title":"Why so many sperm cells?","volume":"8","author":"Reynaud","year":"2015","journal-title":"Commun. Integr. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1016\/j.fertnstert.2014.10.021","article-title":"Limitations of semen analysis as a test of male fertility and anticipated needs from newer tests","volume":"102","author":"Wang","year":"2014","journal-title":"Fertil. Steril."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1093\/humupd\/dmp048","article-title":"World Health Organization reference values for human semen characteristics","volume":"16","author":"Cooper","year":"2010","journal-title":"Hum. Reprod. Update"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1111\/j.2047-2927.2012.00042.x","article-title":"High variability in results of semen analysis in andrology laboratories in Tuscany (Italy): The experience of an external quality control (EQC) programme","volume":"1","author":"Filimberti","year":"2013","journal-title":"Andrology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/S0074-7696(03)32004-2","article-title":"Unresolved issues in mammalian fertilization","volume":"232","year":"2003","journal-title":"Int. Rev. Cytol."},{"key":"ref_59","first-page":"567","article-title":"The functional anatomy of the human spermatozoon: Relating ultrastructure and function","volume":"24","author":"Mortimer","year":"2018","journal-title":"Mol. Hum. Reprod."},{"key":"ref_60","first-page":"139","article-title":"Sperm DNA damage and its clinical relevance in assessing reproductive outcome","volume":"6","author":"Sharma","year":"2004","journal-title":"Asian J."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1080\/19396360801957739","article-title":"Sperm DNA Tests as Useful Adjuncts to Semen Analysis","volume":"54","author":"Lewis","year":"2008","journal-title":"Syst. Biol. Reprod. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1007\/s10815-013-9962-8","article-title":"Sperm selection using magnetic activated cell sorting (MACS) in assisted reproduction: A systematic review and meta-analysis","volume":"30","author":"Gil","year":"2013","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1111\/andr.12591","article-title":"ICSI outcomes using testicular spermatozoa in non-azoospermic couples with recurrent ICSI failure and no previous live births","volume":"7","author":"Herrero","year":"2019","journal-title":"Andrology"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Arafa, M., AlMalki, A., AlBadr, M., Burjaq, H., Majzoub, A., AlSaid, S., and Elbardisi, H. (2018). ICSI outcome in patients with high DNA fragmentation: Testicular versus ejaculated spermatozoa. Andrologia, 50.","DOI":"10.1111\/and.12835"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1093\/humupd\/dmn004","article-title":"Oxidative stress and male infertility--a clinical perspective","volume":"14","author":"Tremellen","year":"2008","journal-title":"Hum. Reprod. Update"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Agarwal, A., Panner Selvam, M.K., Arafa, M., Okada, H., Homa, S., Killeen, A., Balaban, B., Saleh, R., Armagan, A., and Roychoudhury, S. (2019). Multi-center evaluation of oxidation-reduction potential by the MiOXSYS in males with abnormal semen. Asian J.","DOI":"10.4103\/aja.aja_5_19"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1071\/RD15325","article-title":"Causes and consequences of oxidative stress in spermatozoa","volume":"28","author":"Aitken","year":"2016","journal-title":"Reprod. Fertil. Dev."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"S697","DOI":"10.21037\/tau.2017.05.25","article-title":"Sperm DNA fragmentation testing: Where we stand in 2017","volume":"6","author":"Tandon","year":"2017","journal-title":"Transl. Urol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1002\/mrd.22072","article-title":"Chromosomal aberrations, Yq microdeletion, and sperm DNA fragmentation in infertile men opting for assisted reproduction","volume":"79","author":"Shamsi","year":"2012","journal-title":"Mol. Reprod. Dev."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.ucl.2013.08.002","article-title":"The office visit","volume":"41","author":"Smith","year":"2014","journal-title":"Urol. Clin. N. Am."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"935","DOI":"10.21037\/tau.2016.10.03","article-title":"Clinical utility of sperm DNA fragmentation testing: Practice recommendations based on clinical scenarios","volume":"5","author":"Agarwal","year":"2016","journal-title":"Transl. Urol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1016\/j.fertnstert.2019.12.015","article-title":"MOXI trial-is it time to stop routinely recommending antioxidant therapy to infertile men?","volume":"113","author":"Kathrins","year":"2020","journal-title":"Fertil. Steril."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"6847","DOI":"10.1093\/nar\/gkv591","article-title":"Chromatin and extracellular vesicle associated sperm RNAs","volume":"43","author":"Johnson","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1530\/REP-10-0322","article-title":"The sperm nucleus: Chromatin, RNA, and the nuclear matrix","volume":"141","author":"Johnson","year":"2011","journal-title":"Reproduction"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1570","DOI":"10.1002\/jcb.21756","article-title":"Paternal contributions: New functional insights for spermatozoal RNA","volume":"104","author":"Lalancette","year":"2008","journal-title":"J. Cell Biochem."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1080\/15592294.2019.1644880","article-title":"Human chromatin remodeler cofactor, RNA interactor, eraser and writer sperm RNAs responding to obesity","volume":"15","author":"Swanson","year":"2019","journal-title":"Epigenetics"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2263","DOI":"10.1093\/nar\/gky1223","article-title":"RNA element discovery from germ cell to blastocyst","volume":"47","author":"Estill","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"295re296","DOI":"10.1126\/scitranslmed.aab1287","article-title":"Absence of sperm RNA elements correlates with idiopathic male infertility","volume":"7","author":"Jodar","year":"2015","journal-title":"Sci. Transl. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1093\/hmg\/ddm012","article-title":"Success and failure in human spermatogenesis as revealed by teratozoospermic RNAs","volume":"16","author":"Platts","year":"2007","journal-title":"Hum. Mol. Genet."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1080\/19396368.2017.1393583","article-title":"Sperm RNA elements as markers of health","volume":"64","author":"Burl","year":"2018","journal-title":"Syst. Biol. Reprod. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"12397","DOI":"10.1038\/s41598-019-48441-5","article-title":"The effects of di-butyl phthalate exposure from medications on human sperm RNA among men","volume":"9","author":"Estill","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.aju.2017.11.016","article-title":"Update on the proteomics of male infertility: A systematic review","volume":"16","author":"Agarwal","year":"2018","journal-title":"Arab. J. Urol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"5426","DOI":"10.1016\/j.jprot.2012.06.021","article-title":"Proteomic characteristics of spermatozoa in normozoospermic patients with infertility","volume":"75","author":"Xu","year":"2012","journal-title":"J. Proteom."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1093\/humrep\/deu073","article-title":"High-throughput sperm differential proteomics suggests that epigenetic alterations contribute to failed assisted reproduction","volume":"29","author":"Azpiazu","year":"2014","journal-title":"Hum. Reprod."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"5403","DOI":"10.1021\/pr501031x","article-title":"Investigation of male infertility using quantitative comparative proteomics","volume":"13","author":"Legare","year":"2014","journal-title":"J. Proteome Res."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Panner Selvam, M.K., Agarwal, A., Pushparaj, P.N., Baskaran, S., and Bendou, H. (2019). Sperm Proteome Analysis and Identification of Fertility-Associated Biomarkers in Unexplained Male Infertility. Genes, 10.","DOI":"10.3390\/genes10070522"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.jbior.2013.07.005","article-title":"Phospholipase C zeta (PLCzeta): Oocyte activation and clinical links to male factor infertility","volume":"53","author":"Amdani","year":"2013","journal-title":"Adv. Biol. Regul."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.jbior.2015.11.009","article-title":"Phospholipase C zeta (PLCzeta) and male infertility: Clinical update and topical developments","volume":"61","author":"Amdani","year":"2016","journal-title":"Adv. Biol. Regul."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1007\/s10815-015-0531-1","article-title":"Phospholipase C-zeta deficiency as a cause for repetitive oocyte fertilization failure during ovarian stimulation for in vitro fertilization with ICSI: A case report","volume":"32","author":"Chithiwala","year":"2015","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1093\/molehr\/gav042","article-title":"Rescue of failed oocyte activation after ICSI in a mouse model of male factor infertility by recombinant phospholipase Czeta","volume":"21","author":"Sanusi","year":"2015","journal-title":"Mol. Hum. Reprod."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2210","DOI":"10.1038\/s41467-018-04678-8","article-title":"A novel atypical sperm centriole is functional during human fertilization","volume":"9","author":"Fishman","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Avidor-Reiss, T. (2018). Rapid Evolution of Sperm Produces Diverse Centriole Structures that Reveal the Most Rudimentary Structure Needed for Function. Cells, 7.","DOI":"10.3390\/cells7070067"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1007\/s00441-010-1007-3","article-title":"The making of abnormal spermatozoa: Cellular and molecular mechanisms underlying pathological spermiogenesis","volume":"341","author":"Chemes","year":"2010","journal-title":"Cell Tissue Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1006\/dbio.1994.1256","article-title":"The centrosome and its mode of inheritance: The reduction of the centrosome during gametogenesis and its restoration during fertilization","volume":"165","author":"Schatten","year":"1994","journal-title":"Dev. Biol."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Avidor-Reiss, T., Mazur, M., Fishman, E.L., and Sindhwani, P. (2019). The Role of Sperm Centrioles in Human Reproduction\u2014The Known and the Unknown. Front. Cell Dev. Biol., 7.","DOI":"10.3389\/fcell.2019.00188"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"b94","DOI":"10.1136\/bmj.b94","article-title":"Preventing transmission of maternally inherited mitochondrial DNA diseases","volume":"338","author":"Poulton","year":"2009","journal-title":"BMJ"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"R1178","DOI":"10.1016\/j.cub.2015.11.015","article-title":"Sperm Centrosomes: Kiss Your Asterless Goodbye, for Fertility\u2019s Sake","volume":"25","author":"Schatten","year":"2015","journal-title":"Curr. Biol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"179","DOI":"10.5468\/ogs.2018.61.2.179","article-title":"Clinical assessment of the male fertility","volume":"61","author":"Khatun","year":"2018","journal-title":"Obs. Gynecol. Sci."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1016\/j.fertnstert.2019.03.005","article-title":"Limits of current male fertility testing","volume":"111","author":"Oehninger","year":"2019","journal-title":"Fertil. Steril."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1136\/jclinpath-2018-205579","article-title":"Investigation and management of subfertility","volume":"72","author":"Thurston","year":"2019","journal-title":"J. Clin. Pathol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1111\/andr.12379","article-title":"Impairment of sperm DNA methylation in male infertility: A meta-analytic study","volume":"5","author":"Santi","year":"2017","journal-title":"Andrology"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.aju.2017.12.001","article-title":"A systematic review on sperm DNA fragmentation in male factor infertility: Laboratory assessment","volume":"16","author":"Agarwal","year":"2018","journal-title":"Arab. J. Urol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"296","DOI":"10.5534\/wjmh.190055","article-title":"Male Oxidative Stress Infertility (MOSI): Proposed Terminology and Clinical Practice Guidelines for Management of Idiopathic Male Infertility","volume":"37","author":"Agarwal","year":"2019","journal-title":"World J. Men\u2019s Health"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1046\/j.1439-0531.2003.00436.x","article-title":"Laboratory semen assessment and prediction of fertility: Still utopia?","volume":"38","year":"2003","journal-title":"Reprod. Domest. Anim. = Zuchthyg."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1111\/j.1439-0531.2006.00764.x","article-title":"Can we increase the estimated value of semen assessment?","volume":"41","year":"2006","journal-title":"Reprod. Domest. Anim. = Zuchthyg."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1002\/j.1939-4640.1993.tb03247.x","article-title":"In vitro evaluation of sperm quality: An opinion","volume":"14","author":"Amann","year":"1993","journal-title":"J. Androl."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1071\/RD17479","article-title":"Implementation of novel statistical procedures and other advanced approaches to improve analysis of CASA data","volume":"30","year":"2018","journal-title":"Reprod. Fertil. Dev."},{"key":"ref_108","unstructured":"Jarow, J., Sigman, M., and Kolettis, P. (2011). The Optimal Evaluation of the Infertile Male: Best Practice Statement, American Urological Association. Reviewed and Validity Confirmed 2011."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"3411","DOI":"10.1093\/hmg\/ddl417","article-title":"Non-invasive genetic diagnosis of male infertility using spermatozoal RNA: KLHL10 mutations in oligozoospermic patients impair homodimerization","volume":"15","author":"Yatsenko","year":"2006","journal-title":"Hum. Mol. Genet."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/4\/990\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:44:50Z","timestamp":1760363090000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/4\/990"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,16]]},"references-count":109,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2020,4]]}},"alternative-id":["cells9040990"],"URL":"https:\/\/doi.org\/10.3390\/cells9040990","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,16]]}}}