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This was achieved by grouping mutations in the following classes: manchette, acrosome, Sertoli cell contact, chromatin remodelling, and mutations involved in complex regulations such as protein (de)phosphorylation and <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> stability, and flagellum\/motility mutations. For all mutant phenotypes, flagellum function (motility) was affected. Head shape, including the nucleus, was also affected in spermatozoa of most mouse models, though with considerable variation. For the mutants that were categorized in the flagellum\/motility group, generally normal head shapes were found, even when the flagellum did not develop or only poorly so. Most mutants are sterile, an occasional one semi\u2010sterile. For completeness, the influence of the sex chromosomes on sperm phenotype is included. Functionally, the genes involved can be categorized as regulators of spermiogenesis. When extrapolating these data to human sperm samples, in vivo selection for motility would be the tool for weeding out the products of suboptimal spermiogenesis and epididymal sperm maturation. The striking dependency of motility on proper sperm head development is not easy to understand, but likely is of evolutionary benefit. Also, sperm competition after mating can never act against the long\u2010term multi\u2010generation interest of genetic integrity. Hence, it is plausible to suggest that short\u2010term haplophase fitness i.e., motility, is developmentally integrated with proper nucleus maturation, including genetic integrity to protect multi\u2010generation fitness. We hypothesize that, when the prime defect is in flagellum formation, apparently a feedback loop was not necessary as head morphogenesis in these mutants is mostly normal. Extrapolating to human\u2010assisted reproductive techniques practice, this analysis would supply the arguments for the development of tools to select for motility as a continuous (non\u2010discrete) parameter.<\/jats:p>","DOI":"10.1111\/andr.300","type":"journal-article","created":{"date-parts":[[2014,12,16]],"date-time":"2014-12-16T07:03:54Z","timestamp":1418713434000},"page":"174-202","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["A mutation study of sperm head shape and motility in the mouse: lessons for the clinic"],"prefix":"10.1111","volume":"3","author":[{"given":"P.","family":"de Boer","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynaecology Radboud University Medical Centre Nijmegen The\u00a0Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"de Vries","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology Radboud University Medical Centre Nijmegen The\u00a0Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Ramos","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology Radboud University Medical Centre Nijmegen The\u00a0Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,12,16]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E06-10-0902"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrd.20963"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.344505"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod64.1.249"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2011.05.050"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2010.12.006"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deh184"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-185X.1970.tb01076.x"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1530\/jrf.0.0330019"},{"key":"e_1_2_13_11_1","doi-asserted-by":"crossref","unstructured":"Ben KhelifaM CouttonC ZouariR KaraouzeneT RenduJ BidartM YassineS PierreV DelarocheJ HennebicqS GrunwaldD EscalierD Pernet\u2010GallayK JoukPS Thierry\u2010MiegN ToureA ArnoultC&RayPF. 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