{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T20:59:34Z","timestamp":1793393974138,"version":"4.5.0"},"reference-count":74,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2023,7,27]],"date-time":"2023-07-27T00:00:00Z","timestamp":1690416000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2023,7,27]],"date-time":"2023-07-27T00:00:00Z","timestamp":1690416000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"name":"Nature and Science Foundation of China","award":["81900609"],"award-info":[{"award-number":["81900609"]}]},{"name":"Nature and Science Foundation of China","award":["81730019"],"award-info":[{"award-number":["81730019"]}]},{"name":"Nature and Science Foundation of Guangdong province","award":["2019B1515120075"],"award-info":[{"award-number":["2019B1515120075"]}]},{"name":"Outstanding Scholar Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory","award":["2018GZR110102004"],"award-info":[{"award-number":["2018GZR110102004"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Biol Toxicol"],"published-print":{"date-parts":[[2023,12]]},"DOI":"10.1007\/s10565-023-09819-4","type":"journal-article","created":{"date-parts":[[2023,7,27]],"date-time":"2023-07-27T00:01:56Z","timestamp":1690416116000},"page":"3077-3100","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Hyperhomocysteinemia lowers serum testosterone concentration via impairing testosterone production in Leydig cells"],"prefix":"10.1007","volume":"39","author":[{"given":"Zhiyuan","family":"Su","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuoliang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjing","family":"Lei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miaomiao","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengxin","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianwei","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manqiu","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andy Peng","family":"Xiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Nie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,7,27]]},"reference":[{"issue":"11","key":"9819_CR1","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.1038\/nmeth.4463","volume":"14","author":"S Aibar","year":"2017","unstructured":"Aibar S, Gonz\u00e1lez-Blas CB, Moerman T, Huynh-Thu VA, Imrichova H, Hulselmans G, et al. SCENIC: single-cell regulatory network inference and clustering. Nat Methods. 2017;14(11):1083\u20136.","journal-title":"Nat Methods"},{"issue":"2","key":"9819_CR2","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1111\/andr.12157","volume":"4","author":"RJ Aitken","year":"2016","unstructured":"Aitken RJ, Flanagan HM, Connaughton H, Whiting S, Hedges A, Baker MA. Involvement of homocysteine, homocysteine thiolactone, and paraoxonase type 1 (PON-1) in the etiology of defective human sperm function. Andrology. 2016;4(2):345\u201360.","journal-title":"Andrology"},{"issue":"13","key":"9819_CR3","doi-asserted-by":"publisher","first-page":"1994","DOI":"10.1093\/hmg\/ddn097","volume":"17","author":"N Akahoshi","year":"2008","unstructured":"Akahoshi N, Kobayashi C, Ishizaki Y, Izumi T, Himi T, Suematsu M, et al. Genetic background conversion ameliorates semi-lethality and permits behavioral analyses in cystathionine \u03b2-synthase-deficient mice, an animal model for hyperhomocysteinemia. Hum Mol Genet. 2008;17(13):1994\u20132005.","journal-title":"Hum Mol Genet"},{"issue":"1","key":"9819_CR4","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1186\/s12958-020-00649-1","volume":"18","author":"F Aliakbari","year":"2020","unstructured":"Aliakbari F, Pouresmaeili F, Eshghifar N, Zolghadr Z, Azizi F. Association of the MTHFR 677C>T and 1298A>C polymorphisms and male infertility risk: a meta-analysis. Reprod Biol Endocrinol RBE. 2020;18(1):93.","journal-title":"Reprod Biol Endocrinol RBE"},{"issue":"3","key":"9819_CR5","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1095\/biolreprod.113.111393","volume":"90","author":"DR Archambeault","year":"2014","unstructured":"Archambeault DR, Yao HH-C. Loss of Smad4 in Sertoli and Leydig Cells Leads to Testicular Dysgenesis and Hemorrhagic Tumor Formation in Mice. Biol Reprod. 2014;90(3):62.","journal-title":"Biol Reprod."},{"issue":"6","key":"9819_CR6","doi-asserted-by":"publisher","first-page":"456","DOI":"10.3390\/biology10060456","volume":"10","author":"MK Arumugam","year":"2021","unstructured":"Arumugam MK, Paal MC, Donohue TM, Ganesan M, Osna NA, Kharbanda KK. Beneficial Effects of Betaine: A Comprehensive Review. Biology. 2021;10(6):456.","journal-title":"Biology"},{"issue":"23","key":"9819_CR7","doi-asserted-by":"publisher","first-page":"6516","DOI":"10.1080\/10408398.2021.1902938","volume":"62","author":"D Ashtary-Larky","year":"2022","unstructured":"Ashtary-Larky D, Bagheri R, Ghanavati M, Asbaghi O, Tinsley GM, Mombaini D, et al. Effects of betaine supplementation on cardiovascular markers: a systematic review and Meta-analysis. Crit Rev Food Sci Nutr. 2022;62(23):6516\u201333.","journal-title":"Crit Rev Food Sci Nutr"},{"issue":"9924","key":"9819_CR8","doi-asserted-by":"publisher","first-page":"1250","DOI":"10.1016\/S0140-6736(13)61126-5","volume":"383","author":"S Basaria","year":"2014","unstructured":"Basaria S. Male hypogonadism. Lancet Lond Engl. 2014;383(9924):1250\u201363.","journal-title":"Lancet Lond Engl"},{"issue":"12","key":"9819_CR9","doi-asserted-by":"publisher","first-page":"1408","DOI":"10.1038\/s41587-020-0591-3","volume":"38","author":"V Bergen","year":"2020","unstructured":"Bergen V, Lange M, Peidli S, Wolf FA, Theis FJ. Generalizing RNA velocity to transient cell states through dynamical modeling. Nat Biotechnol. 2020;38(12):1408\u201314.","journal-title":"Nat Biotechnol"},{"issue":"3","key":"9819_CR10","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1530\/REP-14-0369","volume":"149","author":"F Bergeron","year":"2015","unstructured":"Bergeron F, Nadeau G, Viger RS. GATA4 knockdown in MA-10 Leydig cells identifies multiple target genes in the steroidogenic pathway. Reprod Camb Engl. 2015;149(3):245\u201357.","journal-title":"Reprod Camb Engl"},{"issue":"11","key":"9819_CR11","doi-asserted-by":"publisher","first-page":"1730","DOI":"10.1071\/RD19064","volume":"31","author":"GET Blake","year":"2019","unstructured":"Blake GET, Hall J, Petkovic GE, Watson ED. Analysis of spermatogenesis and fertility in adult mice with a hypomorphic mutation in the Mtrr gene. Reprod Fertil Dev. 2019;31(11):1730\u201341.","journal-title":"Reprod Fertil Dev"},{"issue":"8","key":"9819_CR12","doi-asserted-by":"publisher","first-page":"2616","DOI":"10.3390\/nu13082616","volume":"13","author":"J Brise\u00f1o-Bugar\u00edn","year":"2021","unstructured":"Brise\u00f1o-Bugar\u00edn J, Hern\u00e1ndez-Ochoa I, Araujo-Padilla X, Mojica-Villegas MA, Monta\u00f1o-Gonz\u00e1lez RI, Guti\u00e9rrez-Salme\u00e1n G, et al. Phycobiliproteins ameliorate gonadal toxicity in male mice treated with cyclophosphamide. Nutrients. 2021;13(8):2616.","journal-title":"Nutrients"},{"issue":"5","key":"9819_CR13","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1038\/nbt.4096","volume":"36","author":"A Butler","year":"2018","unstructured":"Butler A, Hoffman P, Smibert P, Papalexi E, Satija R. Integrating single-cell transcriptomic data across different conditions, technologies, and species. Nat Biotechnol. 2018;36(5):411\u201320.","journal-title":"Nat Biotechnol"},{"issue":"18","key":"9819_CR14","doi-asserted-by":"publisher","first-page":"1915","DOI":"10.1101\/gad.17446611","volume":"25","author":"MN Cabili","year":"2011","unstructured":"Cabili MN, Trapnell C, Goff L, Koziol M, Tazon-Vega B, Regev A, et al. Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses. Genes Dev. 2011;25(18):1915\u201327.","journal-title":"Genes Dev"},{"issue":"2","key":"9819_CR15","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1007\/s12011-017-0997-z","volume":"180","author":"Z Cao","year":"2017","unstructured":"Cao Z, Shao B, Xu F, Liu Y, Li Y, Zhu Y. Protective effect of selenium on aflatoxin B1-induced testicular toxicity in mice. Biol Trace Elem Res. 2017;180(2):233\u20138.","journal-title":"Biol Trace Elem Res"},{"issue":"8","key":"9819_CR16","first-page":"2804","volume":"24","author":"NC Chen","year":"2010","unstructured":"Chen NC, Yang F, Capecci LM, Gu Z, Schafer AI, Durante W, et al. Regulation of homocysteine metabolism and methylation in human and mouse tissues. FASEB J Off Publ Fed Am Soc Exp Biol. 2010;24(8):2804\u201317.","journal-title":"FASEB J Off Publ Fed Am Soc Exp Biol"},{"key":"9819_CR17","doi-asserted-by":"publisher","first-page":"871548","DOI":"10.3389\/fendo.2022.871548","volume":"13","author":"A Chi","year":"2022","unstructured":"Chi A, Yang B, Cao X, Wang Z, Liu H, Dai H, et al. ICA II alleviates testicular torsion injury by dampening the oxidative and inflammatory stress. Front Endocrinol. 2022;13:871548.","journal-title":"Front Endocrinol"},{"issue":"1","key":"9819_CR18","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1146\/annurev-animal-020518-115206","volume":"7","author":"CE Clare","year":"2019","unstructured":"Clare CE, Brassington AH, Kwong WY, Sinclair KD. One-carbon metabolism: linking nutritional biochemistry to epigenetic programming of long-term development. Annu Rev Anim Biosci. 2019;7(1):263\u201387.","journal-title":"Annu Rev Anim Biosci"},{"issue":"1","key":"9819_CR19","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","volume":"29","author":"A Dobin","year":"2013","unstructured":"Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S, et al. STAR: ultrafast universal RNA-seq aligner. Bioinforma Oxf Engl. 2013;29(1):15\u201321.","journal-title":"Bioinforma Oxf Engl"},{"issue":"1","key":"9819_CR20","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1007\/s43032-021-00704-1","volume":"29","author":"DP Dos Santos","year":"2022","unstructured":"Dos Santos DP, Ribeiro DF, Frigoli GF, Erthal RP, da Silva Scarton SR, de Lion Siervo GEM, et al. Voluntary exercise attenuates hyperhomocysteinemia, but does not protect against hyperhomocysteinemia-induced testicular and epididymal disturbances. Reprod Sci Thousand Oaks Calif. 2022;29(1):277\u201390.","journal-title":"Reprod Sci Thousand Oaks Calif"},{"issue":"7","key":"9819_CR21","doi-asserted-by":"publisher","first-page":"1725","DOI":"10.1093\/humrep\/del081","volume":"21","author":"IMW Ebisch","year":"2006","unstructured":"Ebisch IMW, Peters WHM, Thomas CMG, Wetzels AMM, Peer PGM, Steegers-Theunissen RPM. Homocysteine, glutathione and related thiols affect fertility parameters in the (sub)fertile couple. Hum Reprod Oxf Engl. 2006;21(7):1725\u201333.","journal-title":"Hum Reprod Oxf Engl"},{"issue":"2","key":"9819_CR22","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1038\/sj.emboj.7601967","volume":"27","author":"JW Edmunds","year":"2008","unstructured":"Edmunds JW, Mahadevan LC, Clayton AL. Dynamic histone H3 methylation during gene induction: HYPB\/Setd2 mediates all H3K36 trimethylation. EMBO J. 2008;27(2):406\u201320.","journal-title":"EMBO J"},{"issue":"1","key":"9819_CR23","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.ymgme.2007.02.001","volume":"91","author":"CL Elmore","year":"2007","unstructured":"Elmore CL, Wu X, Leclerc D, Watson ED, Bottiglieri T, Krupenko NI, et al. Metabolic derangement of methionine and folate metabolism in mice deficient in methionine synthase reductase. Mol Genet Metab. 2007;91(1):85\u201397.","journal-title":"Mol Genet Metab"},{"issue":"9","key":"9819_CR24","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1038\/s41569-019-0211-4","volume":"16","author":"T Gagliano-Juc\u00e1","year":"2019","unstructured":"Gagliano-Juc\u00e1 T, Basaria S. Testosterone replacement therapy and cardiovascular risk. Nat Rev Cardiol. 2019;16(9):555\u201374.","journal-title":"Nat Rev Cardiol"},{"issue":"6","key":"9819_CR25","doi-asserted-by":"publisher","first-page":"2103","DOI":"10.1083\/jcb.201710078","volume":"217","author":"F Gao","year":"2018","unstructured":"Gao F, Li G, Liu C, Gao H, Wang H, Liu W, et al. Autophagy regulates testosterone synthesis by facilitating cholesterol uptake in Leydig cells. J Cell Biol. 2018;217(6):2103\u201319.","journal-title":"J Cell Biol"},{"issue":"5","key":"9819_CR26","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1016\/j.devcel.2018.07.025","volume":"46","author":"CD Green","year":"2018","unstructured":"Green CD, Ma Q, Manske GL, Shami AN, Zheng X, Marini S, et al. A comprehensive roadmap of murine spermatogenesis defined by Single-Cell RNA-Seq. Dev Cell. 2018;46(5):651-667.e10.","journal-title":"Dev Cell"},{"key":"9819_CR27","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/1471-2105-14-7","volume":"14","author":"S H\u00e4nzelmann","year":"2013","unstructured":"H\u00e4nzelmann S, Castelo R, Guinney J. GSVA: gene set variation analysis for microarray and RNA-seq data. BMC Bioinformatics. 2013;14:7.","journal-title":"BMC Bioinformatics"},{"issue":"12","key":"9819_CR28","doi-asserted-by":"publisher","first-page":"3061","DOI":"10.1007\/s00204-016-1669-z","volume":"90","author":"Y Harada","year":"2016","unstructured":"Harada Y, Tanaka N, Ichikawa M, Kamijo Y, Sugiyama E, Gonzalez FJ, et al. PPAR\u03b1-dependent cholesterol\/testosterone disruption in Leydig cells mediates 2,4-dichlorophenoxyacetic acid-induced testicular toxicity in mice. Arch Toxicol. 2016;90(12):3061\u201371.","journal-title":"Arch Toxicol"},{"issue":"12","key":"9819_CR29","doi-asserted-by":"publisher","first-page":"1494","DOI":"10.1093\/eurheartj\/ehq009","volume":"31","author":"R Haring","year":"2010","unstructured":"Haring R, V\u00f6lzke H, Steveling A, Krebs A, Felix SB, Sch\u00f6fl C, et al. Low serum testosterone levels are associated with increased risk of mortality in a population-based cohort of men aged 20\u201379. Eur Heart J. 2010;31(12):1494\u2013501.","journal-title":"Eur Heart J"},{"issue":"4","key":"9819_CR30","doi-asserted-by":"publisher","first-page":"903","DOI":"10.1111\/andr.12703","volume":"8","author":"A Heinrich","year":"2020","unstructured":"Heinrich A, DeFalco T. Essential roles of interstitial cells in testicular development and function. Andrology. 2020;8(4):903\u201314.","journal-title":"Andrology"},{"key":"9819_CR31","doi-asserted-by":"publisher","first-page":"782824","DOI":"10.3389\/fcell.2021.782824","volume":"9","author":"Y Huang","year":"2022","unstructured":"Huang Y, Li X, Sun X, Yao J, Gao F, Wang Z, et al. Anatomical transcriptome atlas of the male mouse reproductive system during aging. Front Cell Dev Biol. 2022;9:782824.","journal-title":"Front Cell Dev Biol"},{"issue":"4","key":"9819_CR32","doi-asserted-by":"publisher","first-page":"e324","DOI":"10.1038\/emm.2017.11","volume":"49","author":"K Hyun","year":"2017","unstructured":"Hyun K, Jeon J, Park K, Kim J. Writing, erasing and reading histone lysine methylations. Exp Mol Med. 2017;49(4):e324\u2013e324.","journal-title":"Exp Mol Med"},{"issue":"1","key":"9819_CR33","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1152\/physrev.00003.2018","volume":"99","author":"H Jakubowski","year":"2019","unstructured":"Jakubowski H. Homocysteine modification in protein structure\/function and human disease. Physiol Rev. 2019;99(1):555\u2013604.","journal-title":"Physiol Rev"},{"issue":"1","key":"9819_CR34","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1159\/000178170","volume":"1","author":"SG Johnsen","year":"1970","unstructured":"Johnsen SG. Testicular biopsy score count \u2013 a method for registration of spermatogenesis in human testes: normal values and results in 335 hypogonadal males. Horm Res Paediatr. 1970;1(1):2\u201325.","journal-title":"Horm Res Paediatr"},{"issue":"8","key":"9819_CR35","first-page":"2752","volume":"24","author":"AR Johnson","year":"2010","unstructured":"Johnson AR, Craciunescu CN, Guo Z, Teng Y-W, Thresher RJ, Blusztajn JK, et al. Deletion of murine choline dehydrogenase results in diminished sperm motility. FASEB J Off Publ Fed Am Soc Exp Biol. 2010;24(8):2752\u201361.","journal-title":"FASEB J Off Publ Fed Am Soc Exp Biol"},{"key":"9819_CR36","doi-asserted-by":"publisher","first-page":"e43966","DOI":"10.7554\/eLife.43966","volume":"8","author":"M Jung","year":"2019","unstructured":"Jung M, Wells D, Rusch J, Ahmad S, Marchini J, Myers SR, et al. Unified single-cell analysis of testis gene regulation and pathology in five mouse strains. eLife. 2019;8:e43966.","journal-title":"eLife"},{"issue":"20","key":"9819_CR37","doi-asserted-by":"publisher","first-page":"E7698","DOI":"10.3390\/ijms21207698","volume":"21","author":"P Kaplan","year":"2020","unstructured":"Kaplan P, Tatarkova Z, Sivonova MK, Racay P, Lehotsky J. Homocysteine and mitochondria in cardiovascular and cerebrovascular systems. Int J Mol Sci. 2020;21(20):E7698.","journal-title":"Int J Mol Sci"},{"issue":"3","key":"9819_CR38","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1095\/biolreprod.104.035238","volume":"72","author":"TLJ Kelly","year":"2005","unstructured":"Kelly TLJ, Neaga OR, Schwahn BC, Rozen R, Trasler JM. Infertility in 5,10-methylenetetrahydrofolate reductase (MTHFR)-deficient male mice is partially alleviated by lifetime dietary betaine supplementation. Biol Reprod. 2005;72(3):667\u201377.","journal-title":"Biol Reprod"},{"issue":"14","key":"9819_CR39","doi-asserted-by":"publisher","first-page":"1712","DOI":"10.1016\/j.devcel.2022.06.008","volume":"57","author":"DG Kirova","year":"2022","unstructured":"Kirova DG, Judasova K, Vorhauser J, Zerjatke T, Leung JK, Glauche I, et al. A ROS-dependent mechanism promotes CDK2 phosphorylation to drive progression through S phase. Dev Cell. 2022;57(14):1712-1727.e9.","journal-title":"Dev Cell"},{"issue":"5","key":"9819_CR40","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1016\/j.jacc.2015.12.005","volume":"67","author":"RA Kloner","year":"2016","unstructured":"Kloner RA, Carson C, Dobs A, Kopecky S, Mohler ER. Testosterone and cardiovascular disease. J Am Coll Cardiol. 2016;67(5):545\u201357.","journal-title":"J Am Coll Cardiol"},{"issue":"22","key":"9819_CR41","doi-asserted-by":"publisher","first-page":"2061","DOI":"10.1016\/j.jchromb.2009.05.039","volume":"877","author":"J Krijt","year":"2009","unstructured":"Krijt J, Dut\u00e1 A, Ko\u017eich V. Determination of S-Adenosylmethionine and S-Adenosylhomocysteine by LC\u2013MS\/MS and evaluation of their stability in mice tissues. J Chromatogr B. 2009;877(22):2061\u20136.","journal-title":"J Chromatogr B"},{"issue":"7719","key":"9819_CR42","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1038\/s41586-018-0414-6","volume":"560","author":"G La Manno","year":"2018","unstructured":"La Manno G, Soldatov R, Zeisel A, Braun E, Hochgerner H, Petukhov V, et al. RNA velocity of single cells. Nature. 2018;560(7719):494\u20138.","journal-title":"Nature"},{"issue":"13","key":"9819_CR43","doi-asserted-by":"publisher","first-page":"1635","DOI":"10.1089\/ars.2017.7397","volume":"30","author":"S Li","year":"2019","unstructured":"Li S, Qiu B, Lu H, Lai Y, Liu J, Luo J, et al. Hyperhomocysteinemia accelerates acute kidney injury to chronic kidney disease progression by downregulating heme oxygenase-1 expression. Antioxid Redox Signal. 2019;30(13):1635\u201350.","journal-title":"Antioxid Redox Signal"},{"issue":"12","key":"9819_CR44","doi-asserted-by":"publisher","first-page":"1739","DOI":"10.1093\/bioinformatics\/btr260","volume":"27","author":"A Liberzon","year":"2011","unstructured":"Liberzon A, Subramanian A, Pinchback R, Thorvaldsd\u00f3ttir H, Tamayo P, Mesirov JP. Molecular signatures database (MSigDB) 3.0. Bioinforma Oxf Engl. 2011;27(12):1739\u201340.","journal-title":"Bioinforma Oxf Engl"},{"issue":"2","key":"9819_CR45","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1159\/000444900","volume":"2","author":"Y Long","year":"2016","unstructured":"Long Y, Nie J. Homocysteine in Renal Injury. Kidney Dis Basel Switz. 2016;2(2):80\u20137.","journal-title":"Kidney Dis Basel Switz"},{"issue":"12","key":"9819_CR46","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","volume":"15","author":"MI Love","year":"2014","unstructured":"Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15(12):550.","journal-title":"Genome Biol"},{"issue":"6","key":"9819_CR47","doi-asserted-by":"publisher","first-page":"1511","DOI":"10.1016\/j.cell.2016.11.016","volume":"167","author":"W Ma","year":"2016","unstructured":"Ma W, Li S, Ma S, Jia L, Zhang F, Zhang Y, et al. Zika virus causes testis damage and leads to male infertility in mice. Cell. 2016;167(6):1511-1524.e10.","journal-title":"Cell"},{"issue":"20","key":"9819_CR48","doi-asserted-by":"publisher","first-page":"7678","DOI":"10.3390\/ijms21207678","volume":"21","author":"C Malecki","year":"2020","unstructured":"Malecki C, Hambly BD, Jeremy RW, Robertson EN. The role of inflammation and myeloperoxidase-related oxidative stress in the pathogenesis of genetically triggered thoracic aortic aneurysms. Int J Mol Sci. 2020;21(20):7678.","journal-title":"Int J Mol Sci"},{"key":"9819_CR49","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1152\/physrev.00019.2018","volume":"99","author":"M-C Meinsohn","year":"2019","unstructured":"Meinsohn M-C, Smith OE, Bertolin K, Murphy BD. The orphan nuclear receptors steroidogenic factor-1 and liver receptor homolog-1: structure, regulation, and essential roles in mammalian reproduction. Physiol Rev. 2019;99:31.","journal-title":"Physiol Rev"},{"issue":"1","key":"9819_CR50","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/aja.1001680102","volume":"168","author":"SC Miller","year":"1983","unstructured":"Miller SC, Bowman BM, Rowland HG. Structure, cytochemistry, endocytic activity, and immunoglobulin (Fc) receptors of rat testicular interstitial-tissue macrophages. Am J Anat. 1983;168(1):1\u201313.","journal-title":"Am J Anat"},{"issue":"5","key":"9819_CR51","doi-asserted-by":"publisher","first-page":"1723","DOI":"10.1016\/S0002-9440(10)64449-5","volume":"161","author":"A Narula","year":"2002","unstructured":"Narula A, Kilen S, Ma E, Kroeger J, Goldberg E, Woodruff TK. Smad4 overexpression causes germ cell ablation and leydig cell hyperplasia in transgenic mice. Am J Pathol. 2002;161(5):1723\u201334.","journal-title":"Am J Pathol"},{"issue":"1","key":"9819_CR52","doi-asserted-by":"publisher","first-page":"15","DOI":"10.2174\/1389200052997366","volume":"6","author":"M Olthof","year":"2005","unstructured":"Olthof M, Verhoef P. Effects of Betaine Intake on Plasma Homocysteine Concentrations and Consequences for Health. Curr Drug Metab. 2005;6(1):15\u201322.","journal-title":"Curr Drug Metab"},{"issue":"7","key":"9819_CR53","doi-asserted-by":"publisher","first-page":"e47","DOI":"10.1093\/nar\/gkv007","volume":"43","author":"ME Ritchie","year":"2015","unstructured":"Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W, et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015;43(7):e47.","journal-title":"Nucleic Acids Res"},{"key":"9819_CR54","doi-asserted-by":"publisher","first-page":"695546","DOI":"10.3389\/fcell.2021.695546","volume":"9","author":"P Sararols","year":"2021","unstructured":"Sararols P, St\u00e9vant I, Neirijnck Y, Rebourcet D, Darbey A, Curley MK, et al. Specific transcriptomic signatures and dual regulation of steroidogenesis between fetal and adult mouse leydig cells. Front Cell Dev Biol. 2021;9:695546.","journal-title":"Front Cell Dev Biol"},{"issue":"3","key":"9819_CR55","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1042\/BJ20030822","volume":"382","author":"BC Schwahn","year":"2004","unstructured":"Schwahn BC, Laryea MD, Chen Z, Melnyk S, Pogribny I, Garrow T, et al. Betaine rescue of an animal model with methylenetetrahydrofolate reductase deficiency. Biochem J. 2004;382(3):831.","journal-title":"Biochem J"},{"key":"9819_CR56","doi-asserted-by":"publisher","first-page":"101322","DOI":"10.1016\/j.redox.2019.101322","volume":"28","author":"W Shen","year":"2020","unstructured":"Shen W, Gao C, Cueto R, Liu L, Fu H, Shao Y, et al. Homocysteine-methionine cycle is a metabolic sensor system controlling methylation-regulated pathological signaling. Redox Biol. 2020;28:101322.","journal-title":"Redox Biol"},{"issue":"6","key":"9819_CR57","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1177\/1933719112459232","volume":"20","author":"K Singh","year":"2013","unstructured":"Singh K, Jaiswal D. One-carbon metabolism, spermatogenesis, and male infertility. Reprod Sci Thousand Oaks Calif. 2013;20(6):622\u201330.","journal-title":"Reprod Sci Thousand Oaks Calif"},{"issue":"3","key":"9819_CR58","doi-asserted-by":"publisher","first-page":"403","DOI":"10.33549\/physiolres.931569","volume":"58","author":"S Slow","year":"2009","unstructured":"Slow S, Lever M, Chambers ST, George PM. Plasma dependent and independent accumulation of betaine in male and female rat tissues. Physiol Res. 2009;58(3):403\u201310.","journal-title":"Physiol Res"},{"issue":"2","key":"9819_CR59","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1016\/j.reprotox.2006.11.003","volume":"23","author":"M S\u00f6nmez","year":"2007","unstructured":"S\u00f6nmez M, Y\u00fcce A, T\u00fcrk G. The protective effects of melatonin and Vitamin E on antioxidant enzyme activities and epididymal sperm characteristics of homocysteine treated male rats. Reprod Toxicol. 2007;23(2):226\u201331.","journal-title":"Reprod Toxicol"},{"issue":"4","key":"9819_CR60","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1016\/S1472-6483(10)61147-9","volume":"11","author":"V Sriraman","year":"2005","unstructured":"Sriraman V, Anbalagan M, Rao AJ. Hormonal regulation of Leydig cell proliferation and differentiation in rodent testis: a dynamic interplay between gonadotrophins and testicular factors. Reprod Biomed Online. 2005;11(4):507\u201318.","journal-title":"Reprod Biomed Online"},{"issue":"6","key":"9819_CR61","doi-asserted-by":"publisher","first-page":"1436","DOI":"10.1016\/j.celrep.2018.10.045","volume":"25","author":"S Suo","year":"2018","unstructured":"Suo S, Zhu Q, Saadatpour A, Fei L, Guo G, Yuan G-C. Revealing the critical regulators of cell identity in the mouse cell atlas. Cell Rep. 2018;25(6):1436-1445.e3.","journal-title":"Cell Rep"},{"issue":"10","key":"9819_CR62","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1515\/CCLM.2005.187","volume":"43","author":"PM Ueland","year":"2005","unstructured":"Ueland PM, Holm PI, Hustad S. Betaine: a key modulator of one-carbon metabolism and homocysteine status. Clin Chem Lab Med. 2005;43(10):1069\u201375.","journal-title":"Clin Chem Lab Med"},{"issue":"3","key":"9819_CR63","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1515\/cclm-2012-0605","volume":"51","author":"TP Vacek","year":"2013","unstructured":"Vacek TP, Kalani A, Voor MJ, Tyagi SC, Tyagi N. The role of homocysteine in bone remodeling. Clin Chem Lab Med. 2013;51(3):579\u201390.","journal-title":"Clin Chem Lab Med"},{"issue":"16","key":"9819_CR64","doi-asserted-by":"publisher","first-page":"1447","DOI":"10.1089\/ars.2016.6968","volume":"28","author":"J Wang","year":"2018","unstructured":"Wang J, Wang W, Li S, Han Y, Zhang P, Meng G, et al. Hydrogen sulfide as a potential target in preventing spermatogenic failure and testicular dysfunction. Antioxid Redox Signal. 2018;28(16):1447\u201362.","journal-title":"Antioxid Redox Signal"},{"issue":"4","key":"9819_CR65","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/j.cels.2018.11.005","volume":"8","author":"SL Wolock","year":"2019","unstructured":"Wolock SL, Lopez R, Klein AM. Scrublet: computational identification of cell doublets in single-cell transcriptomic data. Cell Syst. 2019;8(4):281-291.e9.","journal-title":"Cell Syst"},{"issue":"11","key":"9819_CR66","doi-asserted-by":"publisher","first-page":"100792","DOI":"10.1016\/j.xcrm.2022.100792","volume":"3","author":"K Xia","year":"2022","unstructured":"Xia K, Wang F, Lai X, Dong L, Luo P, Zhang S, et al. AAV-mediated gene therapy produces fertile offspring in the Lhcgr-deficient mouse model of Leydig cell failure. Cell Rep Med. 2022;3(11):100792.","journal-title":"Cell Rep Med"},{"issue":"8","key":"9819_CR67","doi-asserted-by":"publisher","first-page":"2517","DOI":"10.1016\/j.clnu.2019.11.011","volume":"39","author":"L Xie","year":"2020","unstructured":"Xie L, Zhao B, Luo J, Li Y, Zhu F, Li G, et al. A U-shaped association between serum betaine and incident risk of first ischemic stroke in hypertensive patients. Clin Nutr. 2020;39(8):2517\u201324.","journal-title":"Clin Nutr"},{"issue":"3","key":"9819_CR68","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1177\/1933719113497283","volume":"21","author":"Q Xue","year":"2014","unstructured":"Xue Q, Xu Y, Yang H, Zhang L, Shang J, Zeng C, et al. Methylation of a novel CpG island of intron 1 is associated with steroidogenic factor 1 expression in endometriotic stromal cells. Reprod Sci Thousand Oaks Calif. 2014;21(3):395\u2013400.","journal-title":"Reprod Sci Thousand Oaks Calif"},{"issue":"38","key":"9819_CR69","doi-asserted-by":"publisher","first-page":"29318","DOI":"10.1074\/jbc.M002725200","volume":"275","author":"P Yi","year":"2000","unstructured":"Yi P, Melnyk S, Pogribna M, Pogribny IP, Hine RJ, James SJ. Increase in plasma homocysteine associated with parallel increases in plasma S-adenosylhomocysteine and lymphocyte DNA hypomethylation. J Biol Chem. 2000;275(38):29318\u201323.","journal-title":"J Biol Chem"},{"issue":"1","key":"9819_CR70","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1002\/stem.2918","volume":"37","author":"B Yin","year":"2019","unstructured":"Yin B, Yu F, Wang C, Li B, Liu M, Ye L. Epigenetic control of mesenchymal stem cell fate decision via histone methyltransferase Ash1l. Stem Cells. 2019;37(1):115\u201327.","journal-title":"Stem Cells"},{"issue":"12","key":"9819_CR71","doi-asserted-by":"publisher","first-page":"giaa151","DOI":"10.1093\/gigascience\/giaa151","volume":"9","author":"MD Young","year":"2020","unstructured":"Young MD, Behjati S. SoupX removes ambient RNA contamination from droplet-based single-cell RNA sequencing data. GigaScience. 2020;9(12):giaa151.","journal-title":"GigaScience"},{"issue":"5","key":"9819_CR72","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1089\/omi.2011.0118","volume":"16","author":"G Yu","year":"2012","unstructured":"Yu G, Wang L-G, Han Y, He Q-Y. clusterProfiler: an R package for comparing biological themes among gene clusters. Omics J Integr Biol. 2012;16(5):284\u20137.","journal-title":"Omics J Integr Biol"},{"issue":"15","key":"9819_CR73","doi-asserted-by":"publisher","first-page":"8520","DOI":"10.1093\/nar\/gkab638","volume":"49","author":"Y Zhang","year":"2021","unstructured":"Zhang Y, Liu T, Hu X, Wang M, Wang J, Zou B, et al. Cell Call: integrating paired ligand\u2013receptor and transcription factor activities for cell\u2013cell communication. Nucleic Acids Res. 2021;49(15):8520\u201334.","journal-title":"Nucleic Acids Res"},{"issue":"12","key":"9819_CR74","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1038\/nrendo.2009.212","volume":"5","author":"M Zitzmann","year":"2009","unstructured":"Zitzmann M. Testosterone deficiency, insulin resistance and the metabolic syndrome. Nat Rev Endocrinol. 2009;5(12):673\u201381.","journal-title":"Nat Rev Endocrinol"}],"container-title":["Cell Biology and Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10565-023-09819-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10565-023-09819-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10565-023-09819-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,2]],"date-time":"2023-12-02T08:06:56Z","timestamp":1701504416000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10565-023-09819-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,27]]},"references-count":74,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2023,12]]}},"alternative-id":["9819"],"URL":"https:\/\/doi.org\/10.1007\/s10565-023-09819-4","relation":{},"ISSN":["0742-2091","1573-6822"],"issn-type":[{"value":"0742-2091","type":"print"},{"value":"1573-6822","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,27]]},"assertion":[{"value":"29 December 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 July 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 July 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare that they have no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declaration of interests"}}]}}