Academic Journal
A Western-style diet exacerbates male infertility in M1ap knockout mice.
| Τίτλος: | A Western-style diet exacerbates male infertility in M1ap knockout mice. |
|---|---|
| Συγγραφείς: | Houston BJ; School of BioSciences and Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC, Australia., Nguyen J; School of BioSciences and Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC, Australia., Rotte N; Institute of Reproductive Genetics, Centre of Medical Genetics, University of Münster, Münster, Germany., Tüttelmann F; Institute of Reproductive Genetics, Centre of Medical Genetics, University of Münster, Münster, Germany., Friedrich C; Institute of Reproductive Genetics, Centre of Medical Genetics, University of Münster, Münster, Germany., Merriner DJ; School of BioSciences and Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC, Australia., O'Connor AE; School of BioSciences and Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC, Australia., O'Bryan MK; School of BioSciences and Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC, Australia., Dunleavy JEM; School of BioSciences and Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC, Australia. |
| Πηγή: | Human reproduction (Oxford, England) [Hum Reprod] 2026 Oct 01; Vol. 41 (10), pp. 1633-1642. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Oxford University Press Country of Publication: England NLM ID: 8701199 Publication Model: Print Cited Medium: Internet ISSN: 1460-2350 (Electronic) Linking ISSN: 02681161 NLM ISO Abbreviation: Hum Reprod Subsets: MEDLINE |
| Imprint Name(s): | Publication: Oxford, UK : Oxford University Press Original Publication: Oxford ; Washington, DC : Published for the European Society of Human Reproduction and Embryology by IRL Press, [c1986- |
| Ιατρικοί όροι (MeSH): | Diet, Western*/adverse effects , Infertility, Male*/etiology , Infertility, Male*/genetics , Prostatic Secretory Proteins*/genetics, Spermatogenesis/genetics ; Testis/pathology ; Animals ; Male ; Mice, Knockout ; Mice ; Mice, Inbred C57BL ; Sperm Motility ; Spermatozoa |
| Περίληψη: | Study Question: 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? Summary Answer: The loss of M1AP and a Western diet separately led to subfertility (a form infertility) in male mice and in combination subfertility was worsened. What Is Known Already: Genetics and lifestyle factors individually play important roles in male infertility aetiology. How lifestyle factors influence common genetic causes of infertility are unknown. Study Design, Size, Duration: We generated knockout M1ap mice (M1ap-/--) 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. Participants/materials, Settings, Methods: C57BL6/J mice: wild type (M1ap+/+) and M1ap knockout (M1ap-/-) at 10-12 (young) weeks or 26-28 weeks 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). Main Results and the Role of Chance: Compared to the individual gene deletion or diet treatments, the combined M1ap-/- 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. Large Scale Data: N/A. Limitations, Reasons for Caution: 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. Wider Implications of the Findings: 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. Funding: 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-Germany 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 'Male Germ Cells' (CRU326, project number 329621271) awarded to F.T. and C.F. Disclosures: N/A. (© The Author(s) 2026. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.) |
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| Grant Information: | APP1120356 National Health and Medical Research Council; 57511796 Australia-Germany Joint Research Co-operation Scheme; Deutsche Forschungsgemeinschaft; DFG, German Research Foundation; 329621271 Clinical Research Unit 'Male Germ Cells' |
| Contributed Indexing: | Keywords: M1AP; Western diet; genetic variants; male infertility; sperm quality |
| Substance Nomenclature: | 0 (Prostatic Secretory Proteins) |
| Entry Date(s): | Date Created: 20260831 Date Completed: 20261005 Latest Revision: 20261007 |
| Update Code: | 20261007 |
| PubMed Central ID: | PMC13635463 |
| DOI: | 10.1093/humrep/deag130 |
| PMID: | 42671480 |
| Βάση Δεδομένων: | MEDLINE |
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