{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:05:26Z","timestamp":1792785926694,"version":"4.5.0"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1120356"],"award-info":[{"award-number":["APP1120356"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Australia\u2013Germany Joint Research Co-operation Scheme","award":["57511796"],"award-info":[{"award-number":["57511796"]}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"DFG, German Research Foundation","id":[{"id":"https:\/\/ror.org\/018mejw64","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Clinical Research Unit \u2018Male Germ Cells\u2019","award":["329621271"],"award-info":[{"award-number":["329621271"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>STUDY QUESTION<\/jats:title>\n                    <jats:p>What are the individual and combined effects of a common genetic cause of human male infertility (loss of M1AP function) and a negative lifestyle factor (a Western diet) on male fertility, spermatogenesis, and sperm quality in mice?<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>SUMMARY ANSWER<\/jats:title>\n                    <jats:p>The loss of M1AP and a Western diet separately led to subfertility (a form infertility) in male mice and in combination subfertility was worsened.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>WHAT IS KNOWN ALREADY<\/jats:title>\n                    <jats:p>Genetics and lifestyle factors individually play important roles in male infertility aetiology. How lifestyle factors influence common genetic causes of infertility are unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>STUDY DESIGN, SIZE, DURATION<\/jats:title>\n                    <jats:p>We generated knockout M1ap mice (M1ap\u2212\/\u2212-) and investigated the effects of genotype (wild type or knockout) and diet (control or Western diet) or genotype and age (young or aged) on male fertility and sperm parameters.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PARTICIPANTS\/MATERIALS, SETTINGS, METHODS<\/jats:title>\n                    <jats:p>C57BL6\/J mice: wild type (M1ap+\/+) and M1ap knockout (M1ap\u2212\/\u2212) at 10\u201312 (young) weeks or 26\u201328\u2009weeks old (aged), on a control of Western (high-fat and high-sugar) diet and age. We evaluated male fertility, testis and epididymis histology, and sperm quality (motility, morphology, and count).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>MAIN RESULTS AND THE ROLE OF CHANCE<\/jats:title>\n                    <jats:p>Compared to the individual gene deletion or diet treatments, the combined M1ap\u2212\/\u2212 and Western diet group had more abnormal germ cells, sloughed germ cells and resulted in fewer pups per litter. In accordance, sperm motility and morphology in the combination group were more significantly compromised compared to individual experimental groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>LARGE SCALE DATA<\/jats:title>\n                    <jats:p>N\/A.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>LIMITATIONS, REASONS FOR CAUTION<\/jats:title>\n                    <jats:p>While the mutant mouse mimics the genetic variants seen in many infertile men, this is a mouse model study, meaning findings should be validated in a human cohort where possible.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>WIDER IMPLICATIONS OF THE FINDINGS<\/jats:title>\n                    <jats:p>Taken together, our data highlight that genetic and lifestyle factors can interact to exacerbate male infertility. This study sets a precedent for an improved consideration of how genetic, lifestyle and environmental factors contribute to infertility aetiology. These data inform a clinical foundation for lifestyle interventions for men presenting at infertility clinics prior to medically assisted reproduction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>FUNDING<\/jats:title>\n                    <jats:p>This project was supported by a Society for Reproductive Biology Career Development Award to B.J.H., National Health and Medical Research Council project grant (APP1120356) awarded to M.K.O.B., an Australia\u2013Germany Joint Research Co-operation Scheme (UA-DAAD) grant (57511796) awarded to M.K.O.B., J.E.M.D., and F.T., and the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) within the Clinical Research Unit \u2018Male Germ Cells\u2019 (CRU326, project number 329621271) awarded to F.T. and C.F.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCLOSURES<\/jats:title>\n                    <jats:p>N\/A.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/humrep\/deag130","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T11:54:24Z","timestamp":1784807664000},"page":"1633-1642","source":"Crossref","is-referenced-by-count":0,"title":["A Western-style diet exacerbates male infertility in\n                    <i>M1ap<\/i>\n                    knockout mice"],"prefix":"10.1093","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1078-756X","authenticated-orcid":false,"given":"Brendan J","family":"Houston","sequence":"first","affiliation":[{"name":"School of BioSciences and Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne , Parkville, VIC,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Nguyen","sequence":"additional","affiliation":[{"name":"School of BioSciences and Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne , Parkville, VIC,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadja","family":"Rotte","sequence":"additional","affiliation":[{"name":"Institute of Reproductive Genetics, Centre of Medical Genetics, University of M\u00fcnster , M\u00fcnster,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2745-9965","authenticated-orcid":false,"given":"Frank","family":"T\u00fcttelmann","sequence":"additional","affiliation":[{"name":"Institute of Reproductive Genetics, Centre of Medical Genetics, University of M\u00fcnster , M\u00fcnster,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinna","family":"Friedrich","sequence":"additional","affiliation":[{"name":"Institute of Reproductive Genetics, Centre of Medical Genetics, University of M\u00fcnster , 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