{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T23:59:54Z","timestamp":1793231994439,"version":"4.5.0"},"reference-count":129,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2024,5,24]],"date-time":"2024-05-24T00:00:00Z","timestamp":1716508800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation","doi-asserted-by":"crossref","award":["82371624"],"award-info":[{"award-number":["82371624"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,9,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Klinefelter syndrome (KS) is the most prevalent chromosomal disorder occurring in males. It is defined by an additional X chromosome, 47,XXY, resulting from errors in chromosomal segregation during parental gametogenesis. A major phenotype is impaired reproductive function, in the form of low testosterone and infertility. This review comprehensively examines the genetic and physiological factors contributing to infertility in KS, in addition to emergent assisted reproductive technologies, and the unique ethical challenges KS patients face when seeking infertility treatment. The pathology underlying KS is increased susceptibility for meiotic errors during spermatogenesis, resulting in aneuploid or even polyploid gametes. Specific genetic elements potentiating this susceptibility include polymorphisms in checkpoint genes regulating chromosomal synapsis and segregation. Physiologically, the additional sex chromosome also alters testicular endocrinology and metabolism by dysregulating interstitial and Sertoli cell function, collectively impairing normal sperm development. Additionally, epigenetic modifications like aberrant DNA methylation are being increasingly implicated in these disruptions. We also discuss assisted reproductive approaches leveraged in infertility management for KS patients. Application of assisted reproductive approaches, along with deep comprehension of the meiotic and endocrine disturbances precipitated by supernumerary X chromosomes, shows promise in enabling biological parenthood for KS individuals. This will require continued multidisciplinary collaboration between experts with background of genetics, physiology, ethics, and clinical reproductive medicine.<\/jats:p>","DOI":"10.1093\/biolre\/ioae076","type":"journal-article","created":{"date-parts":[[2024,5,24]],"date-time":"2024-05-24T12:43:28Z","timestamp":1716554608000},"page":"516-528","source":"Crossref","is-referenced-by-count":7,"title":["Klinefelter syndrome: etiology and clinical considerations in male infertility"],"prefix":"10.1093","volume":"111","author":[{"given":"Xinyue","family":"Chen","sequence":"first","affiliation":[{"name":"Reproductive Endocrinology and Regulation Laboratory , Department of Obstetric and Gynecologic, , Chengdu 610041 , China"},{"name":"West China Second University Hospital, Sichuan University , Department of Obstetric and Gynecologic, , Chengdu 610041 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueguang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Reproductive Endocrinology and Regulation Laboratory , Department of Obstetric and Gynecologic, , Chengdu 610041 , China"},{"name":"West China Second University Hospital, Sichuan University , Department of Obstetric and Gynecologic, , Chengdu 610041 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Jiang","sequence":"additional","affiliation":[{"name":"Reproductive Endocrinology and Regulation Laboratory , Department of Obstetric and Gynecologic, , Chengdu 610041 , China"},{"name":"West China Second University Hospital, Sichuan University , Department of Obstetric and Gynecologic, , Chengdu 610041 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenming","family":"Xu","sequence":"additional","affiliation":[{"name":"Reproductive Endocrinology and Regulation Laboratory , Department of Obstetric and Gynecologic, , Chengdu 610041 , China"},{"name":"West China Second University Hospital, Sichuan University , Department of Obstetric and Gynecologic, , Chengdu 610041 , China"},{"name":"Key Laboratory of Obstetric , Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, , Chengdu 610041 , China"},{"name":"West China Second University Hospital, Sichuan University\u2014The Chinese University of Hong Kong (SCU-CUHK) Joint Laboratory for Reproductive Medicine , Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, , Chengdu 610041 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,5,24]]},"reference":[{"key":"2024091602111017000_ref1","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/S0140-6736(04)16678-6","article-title":"Klinefelter's 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