{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T11:10:45Z","timestamp":1782472245747,"version":"3.54.5"},"reference-count":59,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T00:00:00Z","timestamp":1739404800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["F31AR079845, T31AR007465"],"award-info":[{"award-number":["F31AR079845, T31AR007465"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100012756","name":"Lalor Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100012756","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["rep.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,2,13]]},"abstract":"<jats:sec>\n                    <jats:title>In brief<\/jats:title>\n                    <jats:p>Germ-free mice display epididymal transcriptomic changes that were also evident in their conventionalized male offspring and mice lacking T and B cells. This paper demonstrates the role of microbiota and immune cells in the epididymis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>The microbiome encompasses the array of microorganisms inhabiting various niches in the body and is necessary for numerous physiological processes, including normal metabolism and a functioning immune system. Not only does the absence of a microbiome in mice impact the exposed animals but also inherited phenotypes in successive generations of progeny, suggesting that the absence of a microbiome impacts the germline and gametes. Indeed, recent research has identified a role of the gut microbiome in contributing to male fertility, in both healthy and disease states. While this link is beginning to be established, the impact of the microbiome on the male reproductive tract remains understudied. Here, we utilized a germ-free mouse model to examine the influence of the absence of microbes on the male reproductive tract. In contrast to mice with an established microbiome, germ-free mice display decreased testicular weight and the prevalence of an epididymitis-like inflammation phenotype. These histopathological changes are accompanied by transcriptomic dysregulation in the reproductive tract of germ-free mice, particularly in the cauda epididymis. Moreover, these transcriptomic changes are transmitted to the next generation with high correlation of gene expression in the cauda epididymis between germ-free mice and their conventionalized (microbiome-restored) male offspring, when compared to control mice. Ultimately, our findings identify the reproductive sequalae of males without a functional microbiome and additionally in their conventionalized offspring, suggesting that the paternal microbiota is an underappreciated contributor to male reproductive function.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1530\/rep-24-0204","type":"journal-article","created":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T11:36:29Z","timestamp":1739446589000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-11","source":"Crossref","is-referenced-by-count":5,"title":["A lack of commensal microbiota influences the male reproductive tract intergenerationally in mice"],"prefix":"10.1093","volume":"169","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8999-5731","authenticated-orcid":true,"given":"Natalie A","family":"Trigg","sequence":"first","affiliation":[{"name":"Division of Neonatology, The Children\u2019s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA"},{"name":"Departments of Genetics and Pediatrics \u2013 Penn Epigenetics Institute, Institute of Regenerative Medicine, and Center for Reproduction and Women\u2019s Health, University of Pennsylvania Perelman School of Medicine. Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon K","family":"Zhou","sequence":"additional","affiliation":[{"name":"Departments of Genetics and Pediatrics \u2013 Penn Epigenetics Institute, Institute of Regenerative Medicine, and Center for Reproduction and Women\u2019s Health, University of Pennsylvania Perelman School of Medicine. Philadelphia, Pennsylvania, USA"},{"name":"Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan C","family":"Harris","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA"},{"name":"Department of Dermatology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeline N","family":"Lamonica","sequence":"additional","affiliation":[{"name":"Division of Neonatology, The Children\u2019s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA"},{"name":"Departments of Genetics and Pediatrics \u2013 Penn Epigenetics Institute, Institute of Regenerative Medicine, and Center for Reproduction and Women\u2019s Health, University of Pennsylvania Perelman School of Medicine. Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Molly A","family":"Nelson","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease, Department of Pediatrics, The Children\u2019s Hospital of Philadelphia. Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A","family":"Silverman","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease, Department of Pediatrics, The Children\u2019s Hospital of Philadelphia. Philadelphia, Pennsylvania, USA"},{"name":"Institute for Immunology and Immune Health and Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA"},{"name":"Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philapdelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taku","family":"Kambayashi","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7915-0463","authenticated-orcid":true,"given":"Colin C","family":"Conine","sequence":"additional","affiliation":[{"name":"Division of Neonatology, The Children\u2019s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA"},{"name":"Departments of Genetics and Pediatrics \u2013 Penn Epigenetics Institute, Institute of Regenerative Medicine, and Center for Reproduction and Women\u2019s Health, University of Pennsylvania Perelman School of Medicine. Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","reference":[{"key":"bib1","series-title":"PLoS One","article-title":"The gut microbiota and developmental programming of the testis in mice","volume":"9","author":"Al-Asmakh M","year":"2014","unstructured":"Al-Asmakh M\n, \nStukenborg J-B\n, \nReda A\n, et al.\n 2014 The gut microbiota and developmental programming of the testis in mice. PLoS One 9 e103809. (https:\/\/doi.org\/10.1371\/journal.pone.0103809)"},{"key":"bib2","series-title":"Methods Cell Biol etc","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/B978-0-12-407239-8.00013-6","article-title":"Chapter 13 \u2013 Quantitative 3D cell-based assay performed with cellular spheroids and fluorescence microscopy","volume":"113","author":"Ansari N","year":"2013","unstructured":"Ansari N\n, \nM\u00fcller S\n, \nStelzer EHK\n, et al\n. 2013 Chapter 13 \u2013 Quantitative 3D cell-based assay performed with cellular spheroids and fluorescence microscopy. Methods Cell Biol etc 113, 295\u2013309. (https:\/\/doi.org\/10.1016\/B978-0-12-407239-8.00013-6)"},{"key":"bib3","series-title":"Nature","first-page":"652","article-title":"Paternal microbiome perturbations impact offspring fitness","volume":"629","author":"Argaw-Denboba A","year":"2024","unstructured":"Argaw-Denboba A\n, \nSchmidt TSB\n, \nDi Giacomo M\n, et al.\n 2024 Paternal microbiome perturbations impact offspring fitness. Nature 629 652\u2013659. (https:\/\/doi.org\/10.1038\/s41586-024-07336-w)"},{"key":"bib4","series-title":"Fertil Steril","first-page":"1700","article-title":"Paternal body mass index is associated with decreased blastocyst development and reduced live birth rates following assisted reproductive technology","volume":"95","author":"Bakos HW","year":"2011","unstructured":"Bakos HW\n, \nHenshaw RC\n, \nMitchell M\n, et al.\n 2011 Paternal body mass index is associated with decreased blastocyst development and reduced live birth rates following assisted reproductive technology. Fertil Steril 95 1700\u20131704. (https:\/\/doi.org\/10.1016\/j.fertnstert.2010.11.044)"},{"key":"bib5","series-title":"Proc Natl Acad Sci U S A","article-title":"Regulatory T cells play a crucial role in maintaining sperm tolerance and male fertility","volume":"120","author":"Barrachina F","year":"2023","unstructured":"Barrachina F\n, \nOttino K\n, \nElizagaray ML\n, et al.\n 2023 Regulatory T cells play a crucial role in maintaining sperm tolerance and male fertility. Proc Natl Acad Sci U S A 120 e2306797120. (https:\/\/doi.org\/10.1073\/pnas.2306797120)"},{"key":"bib6","series-title":"Front Immunol","article-title":"Immune cell subtypes and their function in the testis","volume":"11","author":"Bhushan S","year":"2020","unstructured":"Bhushan S\n, \nTheas MS\n, \nGuazzone VA\n, et al.\n 2020 Immune cell subtypes and their function in the testis. Front Immunol 11 583304. (https:\/\/doi.org\/10.3389\/fimmu.2020.583304)"},{"key":"bib7","series-title":"Environ Epigenetics","article-title":"Paternal transmission of behavioural and metabolic traits induced by postnatal stress to the 5th generation in mice","volume":"8","author":"Boscardin C","year":"2022","unstructured":"Boscardin C\n, \nManuella F\n & \nMansuy IM\n\n 2022 Paternal transmission of behavioural and metabolic traits induced by postnatal stress to the 5th generation in mice. Environ Epigenetics 8 dvac024. (https:\/\/doi.org\/10.1093\/eep\/dvac024)"},{"key":"bib8","series-title":"Nat Rev Urol","first-page":"727","article-title":"Male infertility and somatic health \u2013 insights into lipid damage as a mechanistic link","volume":"19","author":"Burke ND","year":"2022","unstructured":"Burke ND\n, \nNixon B\n, \nRoman SD\n, et al.\n 2022 Male infertility and somatic health \u2013 insights into lipid damage as a mechanistic link. Nat Rev Urol 19 727\u2013750. (https:\/\/doi.org\/10.1038\/s41585-022-00640-y)"},{"key":"bib9","series-title":"Science","article-title":"Thymic stromal lymphopoietin induces adipose loss through sebum hypersecretion","volume":"373","author":"Choa R","year":"2021","unstructured":"Choa R\n, \nTohyama J\n, \nWada S\n, et al.\n 2021 Thymic stromal lymphopoietin induces adipose loss through sebum hypersecretion. Science 373 eabd2893. (https:\/\/doi.org\/10.1126\/science.abd2893)"},{"key":"bib10","series-title":"Nutrients","first-page":"2818","article-title":"Consequences of paternal nutrition on offspring health and disease","volume":"13","author":"Dimofski P","year":"2021","unstructured":"Dimofski P\n, \nMeyre D\n, \nDreumont N\n, et al.\n 2021 Consequences of paternal nutrition on offspring health and disease. Nutrients 13 2818. (https:\/\/doi.org\/10.3390\/nu13082818)"},{"key":"bib11","series-title":"Hum Reprod","first-page":"1391","article-title":"Diet-induced paternal obesity in the absence of diabetes diminishes the reproductive health of two subsequent generations of mice","volume":"27","author":"Fullston T","year":"2012","unstructured":"Fullston T\n, \nPalmer NO\n, \nOwens JA\n, et al.\n 2012 Diet-induced paternal obesity in the absence of diabetes diminishes the reproductive health of two subsequent generations of mice. Hum Reprod 27 1391\u20131400. (https:\/\/doi.org\/10.1093\/humrep\/des030)"},{"key":"bib12","series-title":"FASEB J","first-page":"4226","article-title":"Paternal obesity initiates metabolic disturbances in two generations of mice with incomplete penetrance to the F2 generation and alters the transcriptional profile of testis and sperm microRNA content","volume":"27","author":"Fullston T","year":"2013","unstructured":"Fullston T\n, \nTeague EMCO\n, \nPalmer NO\n, et al.\n 2013 Paternal obesity initiates metabolic disturbances in two generations of mice with incomplete penetrance to the F2 generation and alters the transcriptional profile of testis and sperm microRNA content. FASEB J 27 4226\u20134243. (https:\/\/doi.org\/10.1096\/fj.12-224048)"},{"key":"bib13","series-title":"Physiol Rep","first-page":"e12336","article-title":"Paternal obesity induces metabolic and sperm disturbances in male offspring that are exacerbated by their exposure to an \u201cobesogenic\u201d diet","volume":"3","author":"Fullston T","year":"2015","unstructured":"Fullston T\n, \nMcPherson NO\n, \nOwens JA\n, et al.\n 2015 Paternal obesity induces metabolic and sperm disturbances in male offspring that are exacerbated by their exposure to an \u201cobesogenic\u201d diet. Physiol Rep 3 e12336. (https:\/\/doi.org\/10.14814\/phy2.12336)"},{"key":"bib14","series-title":"Andrology","first-page":"712","article-title":"Of vessels and cells: the spatial organization of the epididymal immune system","volume":"7","author":"Guiton R","year":"2019","unstructured":"Guiton R\n, \nVoisin A\n, \nHenry-Berger J\n, et al.\n 2019 Of vessels and cells: the spatial organization of the epididymal immune system. Andrology 7 712\u2013718. (https:\/\/doi.org\/10.1111\/andr.12637)"},{"key":"bib15","series-title":"Microbiol Spectr","article-title":"Gut microbiota-testis axis: FMT mitigates high-fat diet-diminished male fertility via improving systemic and testicular metabolome","volume":"10","author":"Hao Y","year":"2022a","unstructured":"Hao Y\n, \nFeng Y\n, \nYan X\n, et al.\n 2022a Gut microbiota-testis axis: FMT mitigates high-fat diet-diminished male fertility via improving systemic and testicular metabolome. Microbiol Spectr 10 e0002822. (https:\/\/doi.org\/10.1128\/spectrum.00028-22)"},{"key":"bib16","series-title":"Mol Med","first-page":"45","article-title":"Gut microbiota-testis axis: FMT improves systemic and testicular micro-environment to increase semen quality in type 1 diabetes","volume":"28","author":"Hao Y","year":"2022b","unstructured":"Hao Y\n, \nFeng Y\n, \nYan X\n, et al.\n 2022b Gut microbiota-testis axis: FMT improves systemic and testicular micro-environment to increase semen quality in type 1 diabetes. Mol Med 28 45. (https:\/\/doi.org\/10.1186\/s10020-022-00473-w)"},{"key":"bib17","series-title":"Cell Rep","article-title":"The microbiota and T cells non-genetically modulate inherited phenotypes transgenerationally","volume":"43","author":"Harris JC","year":"2024","unstructured":"Harris JC\n, \nTrigg NA\n, \nGoshu B\n, et al.\n 2024 The microbiota and T cells non-genetically modulate inherited phenotypes transgenerationally. Cell Rep 43 114029. (https:\/\/doi.org\/10.1016\/j.celrep.2024.114029)"},{"key":"bib18","series-title":"Signal Transduct Targeted Ther","first-page":"135","article-title":"Microbiota in health and diseases","volume":"7","author":"Hou K","year":"2022","unstructured":"Hou K\n, \nWu Z-X\n, \nChen X-Y\n, et al.\n 2022 Microbiota in health and diseases. Signal Transduct Targeted Ther 7 135. (https:\/\/doi.org\/10.1038\/s41392-022-00974-4)"},{"key":"bib19","series-title":"Trends Genet","first-page":"373","article-title":"Impact of parental exposure on offspring health in humans","volume":"37","author":"Jawaid A","year":"2021","unstructured":"Jawaid A\n, \nJehle K-L\n & \nMansuy IM\n\n 2021 Impact of parental exposure on offspring health in humans. Trends Genet 37 373\u2013388. (https:\/\/doi.org\/10.1016\/j.tig.2020.10.006)"},{"key":"bib20","series-title":"Front Physiol","first-page":"1534","article-title":"Mouse microbiota models: comparing germ-free mice and antibiotics treatment as tools for modifying gut bacteria","volume":"9","author":"Kennedy EA","year":"2018","unstructured":"Kennedy EA\n, \nKing KY\n & \nBaldridge MT\n\n 2018 Mouse microbiota models: comparing germ-free mice and antibiotics treatment as tools for modifying gut bacteria. Front Physiol 9 1534. (https:\/\/doi.org\/10.3389\/fphys.2018.01534)"},{"key":"bib21","series-title":"Nat Rev Urol","first-page":"102","article-title":"Frequency, morbidity and equity \u2014 the case for increased research on male fertility","volume":"21","author":"Kimmins S","year":"2024","unstructured":"Kimmins S\n, \nAnderson RA\n, \nBarratt CLR\n, et al.\n 2024 Frequency, morbidity and equity \u2014 the case for increased research on male fertility. Nat Rev Urol 21 102\u2013124. (https:\/\/doi.org\/10.1038\/s41585-023-00820-4)"},{"key":"bib22","series-title":"Cell Host Microbe","first-page":"260","article-title":"The dynamics of the human infant gut microbiome in development and in progression toward type 1 diabetes","volume":"17","author":"Kostic AD","year":"2015","unstructured":"Kostic AD\n, \nGevers D\n, \nSiljander H\n, et al.\n 2015 The dynamics of the human infant gut microbiome in development and in progression toward type 1 diabetes. Cell Host Microbe 17 260\u2013273. (https:\/\/doi.org\/10.1016\/j.chom.2015.01.001)"},{"key":"bib23","series-title":"J Exp Med","first-page":"1467","article-title":"MIF signal transduction initiated by binding to CD74","volume":"197","author":"Leng L","year":"2003","unstructured":"Leng L\n, \nMetz CN\n, \nFang Y\n, et al.\n 2003 MIF signal transduction initiated by binding to CD74. J Exp Med 197 1467\u20131476. (https:\/\/doi.org\/10.1084\/jem.20030286)"},{"key":"bib24","series-title":"Sci Rep","article-title":"TYROBP, TLR4 and ITGAM regulated macrophages polarization and immune checkpoints expression in osteosarcoma","volume":"11","author":"Liang T","year":"2021","unstructured":"Liang T\n, \nChen J\n, \nXu G\n, et al.\n 2021 TYROBP, TLR4 and ITGAM regulated macrophages polarization and immune checkpoints expression in osteosarcoma. Sci Rep 11 19315. (https:\/\/doi.org\/10.1038\/s41598-021-98637-x)"},{"key":"bib25","series-title":"Asian J Androl","first-page":"472","article-title":"Damaged male germ cells induce epididymitis in mice","volume":"22","author":"Liu WH","year":"2020","unstructured":"Liu WH\n, \nWang F\n, \nYu XQ\n, et al.\n 2020 Damaged male germ cells induce epididymitis in mice. Asian J Androl 22 472\u2013480. (https:\/\/doi.org\/10.4103\/aja.aja_116_19)"},{"key":"bib26","series-title":"World J Gastroenterol","first-page":"3837","article-title":"Gut microbiota in obesity","volume":"27","author":"Liu BN","year":"2021","unstructured":"Liu BN\n, \nLiu XT\n, \nLiang ZH\n, et al.\n 2021 Gut microbiota in obesity. World J Gastroenterol 27 3837\u20133850. (https:\/\/doi.org\/10.3748\/wjg.v27.i25.3837)"},{"key":"bib27","series-title":"Genome Biol","first-page":"550","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love MI","year":"2014","unstructured":"Love MI\n, \nHuber W\n & \nAnders S\n\n 2014 Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol 15 550. (https:\/\/doi.org\/10.1186\/s13059-014-0550-8)"},{"key":"bib28","series-title":"Cell Host Microbe","first-page":"554","article-title":"Arresting microbiome development limits immune system maturation and resistance to infection in mice","volume":"31","author":"Lubin J-B","year":"2023","unstructured":"Lubin J-B\n, \nGreen J\n, \nMaddux S\n, et al.\n 2023 Arresting microbiome development limits immune system maturation and resistance to infection in mice. Cell Host Microbe 31 554\u2013570.e7. (https:\/\/doi.org\/10.1016\/j.chom.2023.03.006)"},{"key":"bib29","series-title":"Int J Neuropsychopharmacol","first-page":"pyw020","article-title":"Growing up in a bubble: using germ-free animals to assess the influence of the gut microbiota on brain and behavior","volume":"19","author":"Luczynski P","year":"2016","unstructured":"Luczynski P\n, \nMcVey Neufeld KA\n, \nOriach CS\n, et al.\n 2016 Growing up in a bubble: using germ-free animals to assess the influence of the gut microbiota on brain and behavior. Int J Neuropsychopharmacol 19 pyw020. (https:\/\/doi.org\/10.1093\/ijnp\/pyw020)"},{"key":"bib30","series-title":"Nat Rev Immunol","first-page":"478","article-title":"Interactions between commensal intestinal bacteria and the immune system","volume":"4","author":"Macpherson AJ","year":"2004","unstructured":"Macpherson AJ\n & \nHarris NL\n\n 2004 Interactions between commensal intestinal bacteria and the immune system. Nat Rev Immunol 4 478\u2013485. (https:\/\/doi.org\/10.1038\/nri1373)"},{"key":"bib31","series-title":"Mol Syst Biol","first-page":"834","article-title":"The gut microbiota modulates host amino acid and glutathione metabolism in mice","volume":"11","author":"Mardinoglu A","year":"2015","unstructured":"Mardinoglu A\n, \nShoaie S\n, \nBergentall M\n, et al.\n 2015 The gut microbiota modulates host amino acid and glutathione metabolism in mice. Mol Syst Biol 11 834. (https:\/\/doi.org\/10.15252\/msb.20156487)"},{"key":"bib32","series-title":"Bioinformatics","first-page":"785","article-title":"ImmuCellAI-mouse: a tool for comprehensive prediction of mouse immune cell abundance and immune microenvironment depiction","volume":"38","author":"Miao Y-R","year":"2021","unstructured":"Miao Y-R\n, \nXia M\n, \nLuo M\n, et al.\n 2021 ImmuCellAI-mouse: a tool for comprehensive prediction of mouse immune cell abundance and immune microenvironment depiction. Bioinformatics 38 785\u2013791. (https:\/\/doi.org\/10.1093\/bioinformatics\/btab711)"},{"key":"bib33","series-title":"World J Mens Health","first-page":"626","article-title":"Anything new about paternal contribution to reproductive outcomes? A review of the evidence","volume":"39","author":"Montagnoli C","year":"2021","unstructured":"Montagnoli C\n, \nRuggeri S\n, \nCinelli G\n, et al.\n 2021 Anything new about paternal contribution to reproductive outcomes? A review of the evidence. World J Mens Health 39 626\u2013644. (https:\/\/doi.org\/10.5534\/wjmh.200147)"},{"key":"bib34","series-title":"bioRxiv","article-title":"The microbiota extends the reproductive lifespan by safeguarding the ovarian reserve","author":"Munyoki SK","year":"2024","unstructured":"Munyoki SK\n, \nGoff JP\n, \nReshke A\n, et al.\n 2024 The microbiota extends the reproductive lifespan by safeguarding the ovarian reserve. bioRxiv 2024.2009.2013.612929."},{"key":"bib35","series-title":"Int J Obes Suppl","first-page":"10","article-title":"Gut microbiota: a new path to treat obesity","volume":"9","author":"Muscogiuri G","year":"2019","unstructured":"Muscogiuri G\n, \nCantone E\n, \nCassarano S\n, et al.\n 2019 Gut microbiota: a new path to treat obesity. Int J Obes Suppl 9 10\u201319. (https:\/\/doi.org\/10.1038\/s41367-019-0011-7)"},{"key":"bib36","series-title":"Eur J Immunol","first-page":"2336","article-title":"Impaired regulatory T cell function in germ-free mice","volume":"36","author":"Ostman S","year":"2006","unstructured":"Ostman S\n, \nRask C\n, \nWold AE\n, et al.\n 2006 Impaired regulatory T cell function in germ-free mice. Eur J Immunol 36 2336\u20132346. (https:\/\/doi.org\/10.1002\/eji.200535244)"},{"key":"bib37","series-title":"Elife","first-page":"e82193","article-title":"The regional distribution of resident immune cells shapes distinct immunological environments along the murine epididymis","volume":"11","author":"Pleuger C","year":"2022","unstructured":"Pleuger C\n, \nAi D\n, \nHoppe ML\n, et al.\n 2022 The regional distribution of resident immune cells shapes distinct immunological environments along the murine epididymis. Elife 11 e82193. (https:\/\/doi.org\/10.7554\/elife.82193)"},{"key":"bib38","series-title":"J Med Microbiol","first-page":"817","article-title":"Microbial community and metabolomic comparison of irritable bowel syndrome faeces","volume":"60","author":"Ponnusamy K","year":"2011","unstructured":"Ponnusamy K\n, \nChoi JN\n, \nKim J\n, et al.\n 2011 Microbial community and metabolomic comparison of irritable bowel syndrome faeces. J Med Microbiol 60 817\u2013827. (https:\/\/doi.org\/10.1099\/jmm.0.028126-0)"},{"key":"bib39","series-title":"Elife","article-title":"Mitochondrial defects caused by PARL deficiency lead to arrested spermatogenesis and ferroptosis","volume":"12","author":"Radaelli E","year":"2023","unstructured":"Radaelli E\n, \nAssenmacher CA\n, \nVerrelle J\n, et al.\n 2023 Mitochondrial defects caused by PARL deficiency lead to arrested spermatogenesis and ferroptosis. Elife 12 e84710. (https:\/\/doi.org\/10.7554\/elife.84710)"},{"key":"bib40","series-title":"Hum Reprod","first-page":"1740","article-title":"Multigenerational and transgenerational impact of paternal bisphenol A exposure on male fertility in a mouse model","volume":"35","author":"Rahman MS","year":"2020","unstructured":"Rahman MS\n, \nPang W-K\n, \nRyu D-Y\n, et al.\n 2020 Multigenerational and transgenerational impact of paternal bisphenol A exposure on male fertility in a mouse model. Hum Reprod 35 1740\u20131752. (https:\/\/doi.org\/10.1093\/humrep\/deaa139)"},{"key":"bib41","series-title":"Eur Urol","first-page":"1025","article-title":"Are infertile men less healthy than fertile men? Results of a prospective case-control survey","volume":"56","author":"Salonia A","year":"2009","unstructured":"Salonia A\n, \nMatloob R\n, \nGallina A\n, et al.\n 2009 Are infertile men less healthy than fertile men? Results of a prospective case-control survey. Eur Urol 56 1025\u20131032. (https:\/\/doi.org\/10.1016\/j.eururo.2009.03.001)"},{"key":"bib42","series-title":"Reprod Biol Endocrinol","first-page":"3","article-title":"Smoke, alcohol and drug addiction and male fertility","volume":"16","author":"Sansone A","year":"2018","unstructured":"Sansone A\n, \nDi Dato C\n, \nde Angelis C\n, et al.\n 2018 Smoke, alcohol and drug addiction and male fertility. Reprod Biol Endocrinol 16 3. (https:\/\/doi.org\/10.1186\/s12958-018-0320-7)"},{"key":"bib43","series-title":"Reprod Biomed Online","first-page":"717","article-title":"An exploration of the association between male body mass index and semen quality","volume":"23","author":"Shayeb AG","year":"2011","unstructured":"Shayeb AG\n, \nHarrild K\n, \nMathers E\n, et al.\n 2011 An exploration of the association between male body mass index and semen quality. Reprod Biomed Online 23 717\u2013723. (https:\/\/doi.org\/10.1016\/j.rbmo.2011.07.018)"},{"key":"bib44","series-title":"Exp Anim","first-page":"151","article-title":"Normalization of reproductive function in germfree mice following bacterial contamination","volume":"47","author":"Shimizu K","year":"1998","unstructured":"Shimizu K\n, \nMuranaka Y\n, \nFujimura R\n, et al.\n 1998 Normalization of reproductive function in germfree mice following bacterial contamination. Exp Anim 47 151\u2013158. (https:\/\/doi.org\/10.1538\/expanim.47.151)"},{"key":"bib45","series-title":"Res Microbiol","first-page":"192","article-title":"Serum level of sex steroid hormone is associated with diversity and profiles of human gut microbiome","volume":"170","author":"Shin J-H","year":"2019","unstructured":"Shin J-H\n, \nPark Y-H\n, \nSim M\n, et al.\n 2019 Serum level of sex steroid hormone is associated with diversity and profiles of human gut microbiome. Res Microbiol 170 192\u2013201. (https:\/\/doi.org\/10.1016\/j.resmic.2019.03.003)"},{"key":"bib46","series-title":"Fertil Steril","first-page":"1006","article-title":"Effects of medical comorbidity on male infertility and comorbidity treatment on spermatogenesis","volume":"110","author":"Shiraishi K","year":"2018","unstructured":"Shiraishi K\n & \nMatsuyama H\n\n 2018 Effects of medical comorbidity on male infertility and comorbidity treatment on spermatogenesis. Fertil Steril 110 1006\u20131011.e2. (https:\/\/doi.org\/10.1016\/j.fertnstert.2018.07.002)"},{"key":"bib47","series-title":"Sci Rep","first-page":"103","article-title":"Lipopolysaccharide and lipotheicoic acid differentially modulate epididymal cytokine and chemokine profiles and sperm parameters in experimental acute epididymitis","volume":"8","author":"Silva EJR","year":"2018","unstructured":"Silva EJR\n, \nRibeiro CM\n, \nMirim AFM\n, et al.\n 2018 Lipopolysaccharide and lipotheicoic acid differentially modulate epididymal cytokine and chemokine profiles and sperm parameters in experimental acute epididymitis. Sci Rep 8 103. (https:\/\/doi.org\/10.1038\/s41598-017-17944-4)"},{"key":"bib48","series-title":"Proc Natl Acad Sci U S A","first-page":"5497","article-title":"Microbiota promotes systemic T-cell survival through suppression of an apoptotic factor","volume":"114","author":"Soto R","year":"2017","unstructured":"Soto R\n, \nPetersen C\n, \nNovis CL\n, et al.\n 2017 Microbiota promotes systemic T-cell survival through suppression of an apoptotic factor. Proc Natl Acad Sci U S A 114 5497\u20135502. (https:\/\/doi.org\/10.1073\/pnas.1619336114)"},{"key":"bib49","series-title":"Environ Epigenet","article-title":"POHaD: why we should study future fathers","volume":"4","author":"Soubry A","year":"2018","unstructured":"Soubry A\n\n 2018 POHaD: why we should study future fathers. Environ Epigenet 4 dvy007. (https:\/\/doi.org\/10.1093\/eep\/dvy007)"},{"key":"bib50","series-title":"Biol Reprod","first-page":"1774","article-title":"In vitro fertilization with cryopreserved inbred mouse Sperm1","volume":"63","author":"Sztein JM","year":"2000","unstructured":"Sztein JM\n, \nFarley JS\n & \nMobraaten LE\n\n 2000 In vitro fertilization with cryopreserved inbred mouse Sperm1. Biol Reprod 63 1774\u20131780. (https:\/\/doi.org\/10.1095\/biolreprod63.6.1774)"},{"key":"bib51","series-title":"Gut Microbes","first-page":"1","article-title":"A compromised developmental trajectory of the infant gut microbiome and metabolome in atopic eczema","volume":"12","author":"Ta LDH","year":"2020","unstructured":"Ta LDH\n, \nChan JCY\n, \nYap GC\n, et al.\n 2020 A compromised developmental trajectory of the infant gut microbiome and metabolome in atopic eczema. Gut Microbes 12 1\u201322. (https:\/\/doi.org\/10.1080\/19490976.2020.1801964)"},{"key":"bib52","series-title":"Circ Res","first-page":"1183","article-title":"Gut microbiota in cardiovascular health and disease","volume":"120","author":"Tang WH","year":"2017","unstructured":"Tang WH\n, \nKitai T\n & \nHazen SL\n\n 2017 Gut microbiota in cardiovascular health and disease. Circ Res 120 1183\u20131196. (https:\/\/doi.org\/10.1161\/circresaha.117.309715)"},{"key":"bib53","series-title":"Cell Rep","article-title":"Acrylamide modulates the mouse epididymal proteome to drive alterations in the sperm small non-coding RNA profile and dysregulate embryo development","volume":"37","author":"Trigg NA","year":"2021","unstructured":"Trigg NA\n, \nSkerrett-Byrne DA\n, \nXavier MJ\n, et al.\n 2021 Acrylamide modulates the mouse epididymal proteome to drive alterations in the sperm small non-coding RNA profile and dysregulate embryo development. Cell Rep 37 109787. (https:\/\/doi.org\/10.1016\/j.celrep.2021.109787)"},{"key":"bib54","series-title":"Eur J Clin Nutr","first-page":"489","article-title":"Role of the gut microbiome in chronic diseases: a narrative review","volume":"76","author":"Vijay A","year":"2022","unstructured":"Vijay A\n & \nValdes AM\n\n 2022 Role of the gut microbiome in chronic diseases: a narrative review. Eur J Clin Nutr 76 489\u2013501. (https:\/\/doi.org\/10.1038\/s41430-021-00991-6)"},{"key":"bib55","series-title":"Asian J Androl","first-page":"531","article-title":"The epididymal immune balance: a key to preserving male fertility","volume":"21","author":"Voisin A","year":"2019","unstructured":"Voisin A\n, \nSaez F\n, \nDrevet JR\n, et al.\n 2019 The epididymal immune balance: a key to preserving male fertility. Asian J Androl 21 531\u2013539. (https:\/\/doi.org\/10.4103\/aja.aja_11_19)"},{"key":"bib56","series-title":"Cell Tissue Res","first-page":"351","article-title":"Region-specific immune responses to autoimmune epididymitis in the murine reproductive tract","volume":"381","author":"Wijayarathna R","year":"2020","unstructured":"Wijayarathna R\n, \nPasalic A\n, \nNicolas N\n, et al.\n 2020 Region-specific immune responses to autoimmune epididymitis in the murine reproductive tract. Cell Tissue Res 381 351\u2013360. (https:\/\/doi.org\/10.1007\/s00441-020-03215-8)"},{"key":"bib57","series-title":"BMC Genom","first-page":"310","article-title":"DolphinNext: a distributed data processing platform for high throughput genomics","volume":"21","author":"Yukselen O","year":"2020","unstructured":"Yukselen O\n, \nTurkyilmaz O\n, \nOzturk AR\n, et al.\n 2020 DolphinNext: a distributed data processing platform for high throughput genomics. BMC Genom 21 310. (https:\/\/doi.org\/10.1186\/s12864-020-6714-x)"},{"key":"bib58","series-title":"Front Endocrinol","article-title":"The transgenerational transmission of the paternal type 2 diabetes-induced subfertility phenotype","volume":"12","author":"Zatecka E","year":"2021","unstructured":"Zatecka E\n, \nBohuslavova R\n, \nValaskova E\n, et al.\n 2021 The transgenerational transmission of the paternal type 2 diabetes-induced subfertility phenotype. Front Endocrinol 12 763863. (https:\/\/doi.org\/10.3389\/fendo.2021.763863)"},{"key":"bib59","series-title":"J Genet Genomics","first-page":"688","article-title":"Microbiota-mediated shaping of mouse spleen structure and immune function characterized by scRNA-seq and stereo-seq","volume":"50","author":"Zhang Y","year":"2023","unstructured":"Zhang Y\n, \nShen J\n, \nCheng W\n, et al.\n 2023 Microbiota-mediated shaping of mouse spleen structure and immune function characterized by scRNA-seq and stereo-seq. J Genet Genomics 50 688\u2013701. 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