{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T14:22:17Z","timestamp":1787840537753,"version":"build-2784847793"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T00:00:00Z","timestamp":1754956800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:p>\n                    Recent studies have begun to investigate the metabolic and microbiota profiles in semen, yet their association with abnormal sperm morphology, particularly in teratozoospermia, remains insufficiently characterized. Identifying specific metabolites and microbial taxa linked to this condition could improve diagnostics and management for male infertility. This study analyzed semen samples from 231 patients, including 30 patients with teratozoospermia and 30 patients with normal sperm morphology, collected over four seasons in Chongqing, China. Metabolomic profiling by gas chromatography-mass spectrometry (GC-MS) and microbiota composition analysis via 16S ribosomal ribonucleic acid (rRNA) sequencing revealed distinct seasonal metabolomic shifts, with significant changes in summer and autumn. After excluding seasonally affected metabolites, 14 key metabolites were associated with teratozoospermia, including reduced levels of 4-hydroxyphenylpyruvic acid, phenylpyruvic acid, and N-acetyl-L-aspartic acid. These metabolites are involved in pathways related to oxidative stress and energy metabolism in spermatozoa, suggesting that their depletion may contribute to sperm abnormalities. Proteobacteria, Firmicutes, and Actinobacteriota were predominant phyla across all seasons and groups, but significant genus-level fluctuations, such as Acinetobacter and Staphylococcus, were observed. In teratozoospermia, genera such as\n                    <jats:italic toggle=\"yes\">Lactobacillus<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">Limnochordaceae<\/jats:italic>\n                    showed differential abundance, correlating with key metabolites and suggesting potential functional interactions.\n                    <jats:italic toggle=\"yes\">Limnochordaceae<\/jats:italic>\n                    showed a significant positive correlation with undecanoic acid, whereas\n                    <jats:italic toggle=\"yes\">Lactobacillus<\/jats:italic>\n                    showed a negative correlation. These findings highlight that while seasonal changes significantly influence semen metabolomics and microbiota composition, teratozoospermia is characterized by specific, season-independent metabolic and microbial signatures. Our study provides insights into the metabolic and microbial dynamics of semen, suggesting the possibility of developing novel diagnostic tools and therapeutic strategies for male infertility.\n                  <\/jats:p>","DOI":"10.4103\/aja202549","type":"journal-article","created":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T08:00:09Z","timestamp":1754985609000},"page":"196-204","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":1,"title":["Integrated metabolomic and microbiota analysis of semen: seasonal and morphological associations"],"prefix":"10.4103","volume":"28","author":[{"given":"Jie","family":"Zheng","sequence":"first","affiliation":[{"name":"The Center for Reproductive Medicine, Obstetrics and Gynecology Department, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Liao","sequence":"additional","affiliation":[{"name":"The Center for Reproductive Medicine, Obstetrics and Gynecology Department, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Guang","family":"Sun","sequence":"additional","affiliation":[{"name":"The Center for Reproductive Medicine, Obstetrics and Gynecology Department, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Yuan","sequence":"additional","affiliation":[{"name":"The Center for Reproductive Medicine, Obstetrics and Gynecology Department, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Qin","sequence":"additional","affiliation":[{"name":"The Center for Reproductive Medicine, Obstetrics and Gynecology Department, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting-Li","family":"Han","sequence":"additional","affiliation":[{"name":"The Center for Reproductive Medicine, Obstetrics and Gynecology Department, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China"},{"name":"Mass Spectrometry Centre of Maternal-Fetal Medicine, Chongqing Medical University, Chongqing 400010, China"},{"name":"Joint International Research Lab for Reproduction and Development of Ministry of Education of China, Chongqing Medical University, Chongqing 400010, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heng","family":"Zou","sequence":"additional","affiliation":[{"name":"The Center for Reproductive Medicine, Obstetrics and Gynecology Department, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shen","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Center for Reproductive Medicine, Obstetrics and Gynecology Department, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China"},{"name":"Joint International Research Lab for Reproduction and Development of Ministry of Education of China, Chongqing Medical University, Chongqing 400010, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2025,8,12]]},"reference":[{"key":"R1-20260309","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s10020-023-00776-6","article-title":"Small noncoding RNAs and sperm nuclear basic proteins reflect the environmental impact on germ cells","volume":"30","author":"Ferrero","year":"2024","journal-title":"Mol Med"},{"key":"R2-20260309","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1016\/j.fertnstert.2024.03.003","article-title":"Predictors of success after in vitro fertilization","volume":"121","author":"Shingshetty","year":"2024","journal-title":"Fertil Steril"},{"key":"R3-20260309","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1016\/j.envpol.2018.01.021","article-title":"Seasonal variation of semen parameters correlates with environmental temperature and air pollution:a big data analysis over 6 years","volume":"235","author":"Santi","year":"2018","journal-title":"Environ Pollut"},{"key":"R4-20260309","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1111\/j.2047-2927.2013.00092.x","article-title":"Seasonal variation in semen quality in China","volume":"1","author":"Zhang","year":"2013","journal-title":"Andrology"},{"key":"R5-20260309","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1002\/j.1939-4640.2003.tb02666.x","article-title":"Seasonal variation and age-related changes in human semen parameters","volume":"24","author":"Chen","year":"2003","journal-title":"J Androl"},{"key":"R6-20260309","first-page":"150","article-title":"Unraveling the intricacies of the seminal microbiome and its impact on human fertility","volume":"13","author":"Corral-Vazquez","year":"2024","journal-title":"Biology (Basel)"},{"key":"R7-20260309","doi-asserted-by":"crossref","first-page":"e110152","DOI":"10.1371\/journal.pone.0110152","article-title":"Bacterial communities in semen from men of infertile couples:metagenomic sequencing reveals relationships of seminal microbiota to semen quality","volume":"9","author":"Weng","year":"2014","journal-title":"PLoS One"},{"key":"R8-20260309","doi-asserted-by":"crossref","first-page":"180","DOI":"10.3390\/ijms23010180","article-title":"The role of genital tract microbiome in fertility:a systematic review","volume":"23","author":"Vitale","year":"2021","journal-title":"Int J Mol Sci"},{"key":"R9-20260309","doi-asserted-by":"crossref","first-page":"234","DOI":"10.3389\/fmicb.2019.00234","article-title":"Sperm microbiota and its impact on semen parameters","volume":"10","author":"Baud","year":"2019","journal-title":"Front Microbiol"},{"key":"R10-20260309","doi-asserted-by":"crossref","first-page":"1167763","DOI":"10.3389\/fmicb.2023.1167763","article-title":"Mammals'sperm microbiome:current knowledge, challenges, and perspectives on metagenomics of seminal samples","volume":"14","author":"Contreras","year":"2023","journal-title":"Front Microbiol"},{"key":"R11-20260309","doi-asserted-by":"crossref","first-page":"e0211679","DOI":"10.1371\/journal.pone.0211679","article-title":"Metabolomic profiling reveals correlations between spermiogram parameters and the metabolites present in human spermatozoa and seminal plasma","volume":"14","author":"Engeli","year":"2019","journal-title":"PLoS One"},{"key":"R12-20260309","doi-asserted-by":"crossref","first-page":"1058250","DOI":"10.3389\/fendo.2022.1058250","article-title":"A new perspective on semen quality of aged male:the characteristics of metabolomics and proteomics","volume":"13","author":"Guo","year":"2023","journal-title":"Front Endocrinol"},{"issue":"Suppl 1","key":"R13-20260309","doi-asserted-by":"crossref","first-page":"deab127.015","DOI":"10.1093\/humrep\/deab127.015","article-title":"Differential seminal metabolomic signature is related to sperm quality","volume":"36","author":"Molina","year":"2021","journal-title":"Hum Reprod"},{"key":"R14-20260309","doi-asserted-by":"crossref","first-page":"1859","DOI":"10.1111\/andr.12882","article-title":"Metabolomic signature of the seminal plasma in men with severe oligoasthenospermia","volume":"8","author":"Boguenet","year":"2020","journal-title":"Andrology"},{"key":"R15-20260309","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.fertnstert.2021.12.012","article-title":"other Editorial Board Members of the WHO Laboratory Manual for the Examination and Processing of Human Semen. The sixth edition of the WHO Laboratory Manual for the Examination and Processing of Human Semen:ensuring quality and standardization in basic examination of human ejaculates","volume":"117","author":"Bjorndahl","year":"2022","journal-title":"Fertil Steril"},{"key":"R16-20260309","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.1038\/nprot.2010.108","article-title":"Analytical platform for metabolome analysis of microbial cells using methyl chloroformate derivatization followed by gas chromatography-mass spectrometry","volume":"5","author":"Smart","year":"2010","journal-title":"Nat Protoc"},{"key":"R17-20260309","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.chemolab.2004.12.011","article-title":"Performance of some variable selection methods when multicollinearity is present","volume":"78","author":"Chong","year":"2005","journal-title":"Chemometr Intell Lab"},{"key":"R18-20260309","doi-asserted-by":"crossref","first-page":"W398","DOI":"10.1093\/nar\/gkae253","article-title":"MetaboAnalyst 6.0:towards a unified platform for metabolomics data processing, analysis and interpretation","volume":"52","author":"Pang","year":"2024","journal-title":"Nucleic Acids Res"},{"key":"R19-20260309","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1111\/j.1654-1103.2003.tb02228.x","article-title":"VEGAN, a package of R functions for community ecology","volume":"14","author":"Dixon","year":"2003","journal-title":"J Veg Sci"},{"issue":"Suppl 1","key":"R20-20260309","doi-asserted-by":"crossref","first-page":"qdae001.286","DOI":"10.1093\/jsxmed\/qdae001.286","article-title":"Systematic review and meta-analysis of seasonal variation on human semen quality in the United States","volume":"21","author":"Dehghanbanadaki","year":"2024","journal-title":"J Sex Med"},{"key":"R21-20260309","doi-asserted-by":"crossref","first-page":"1418","DOI":"10.1002\/mrd.23240","article-title":"Seasonal dependence of cadmium molecular effects on Mytilus galloprovincialis (Lamarck, 1819) protamine-like protein properties","volume":"86","author":"Piscopo","year":"2019","journal-title":"Mol Reprod Dev"},{"key":"R22-20260309","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.3390\/biom14081021","article-title":"The multifaceted impact of environmental pollutants on health and ecosystems","volume":"14","author":"Piscopo","year":"2024","journal-title":"Biomolecules"},{"key":"R23-20260309","doi-asserted-by":"crossref","first-page":"114477","DOI":"10.1016\/j.jpba.2021.114477","article-title":"Biomarkers of oxidative stress and antioxidant defense","volume":"209","author":"Demirci-Cekic","year":"2022","journal-title":"J Pharm Biomed Anal"},{"key":"R24-20260309","doi-asserted-by":"crossref","first-page":"33","DOI":"10.3389\/fcimb.2012.00033","article-title":"Staphylococcal response to oxidative stress","volume":"2","author":"Gaupp","year":"2012","journal-title":"Front Cell Infect Microbiol"},{"key":"R25-20260309","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1038\/aja.2010.182","article-title":"Antioxidant therapy in male infertility:fact or fiction?","volume":"13","author":"Zini","year":"2011","journal-title":"Asian J Androl"},{"issue":"Suppl 1","key":"R26-20260309","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/j.1600-0897.2011.01033.x","article-title":"Seminal plasma proteins:what role do they play?","volume":"66","author":"Rodriguez-Martinez","year":"2011","journal-title":"Am J Reprod Immunol"},{"key":"R27-20260309","doi-asserted-by":"crossref","first-page":"31","DOI":"10.4103\/1008-682X.122203","article-title":"Oxidative stress and male reproductive health","volume":"16","author":"Aitken","year":"2014","journal-title":"Asian J Androl"},{"key":"R28-20260309","doi-asserted-by":"crossref","first-page":"369","DOI":"10.3389\/fendo.2018.00369","article-title":"Cholesterol:a gatekeeper of male fertility?","volume":"9","author":"Sedes","year":"2018","journal-title":"Front Endocrinol (Lausanne)"},{"key":"R29-20260309","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s12302-021-00585-w","article-title":"Impact of environmental factors on human semen quality and male fertility:a narrative review","volume":"34","author":"Kumar","year":"2022","journal-title":"Environ Sci Eur"},{"key":"R30-20260309","doi-asserted-by":"crossref","first-page":"15579883241237505","DOI":"10.1177\/15579883241237505","article-title":"Impact of season variation on semen quality:a comprehensive retrospective analysis of data from patients at an eastern Iranian tertiary care fertility center over a decade","volume":"18","author":"Pakmanesh","year":"2024","journal-title":"Am J Mens Health"},{"key":"R31-20260309","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s12958-019-0468-9","article-title":"Effects of N-acetyl-cysteine supplementation on sperm quality, chromatin integrity and level of oxidative stress in infertile men","volume":"17","author":"Jannatifar","year":"2019","journal-title":"Reprod Biol Endocrinol"},{"key":"R32-20260309","doi-asserted-by":"crossref","first-page":"1939","DOI":"10.3892\/etm.2014.2019","article-title":"Protective effects of N-acetylcysteine on cisplatin-induced oxidative stress and DNA damage in HepG2 cells","volume":"8","author":"Wang","year":"2014","journal-title":"Exp Ther Med"},{"key":"R33-20260309","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.pharmthera.2013.09.006","article-title":"Existing and potential therapeutic uses for N-acetylcysteine:the need for conversion to intracellular glutathione for antioxidant benefits","volume":"141","author":"Rushworth","year":"2014","journal-title":"Pharmacol Ther"},{"key":"R34-20260309","doi-asserted-by":"crossref","first-page":"1119153","DOI":"10.3389\/fvets.2023.1119153","article-title":"Regulation of semen quality by fatty acids in diets, extender, and semen","volume":"10","author":"Yuan","year":"2023","journal-title":"Front Vet Sci"},{"key":"R35-20260309","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1038\/s41556-022-00853-8","article-title":"Itaconate inhibits TET DNA dioxygenases to dampen inflammatory responses","volume":"24","author":"Chen","year":"2022","journal-title":"Nat Cell Biol"},{"key":"R36-20260309","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1038\/s42255-022-00577-x","article-title":"Citraconate inhibits ACOD1 (IRG1) catalysis, reduces interferon responses and oxidative stress, and modulates inflammation and cell metabolism","volume":"4","author":"Chen","year":"2022","journal-title":"Nat Metab"},{"key":"R37-20260309","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1016\/j.fertnstert.2013.07.1991","article-title":"Microbiota of the seminal fluid from healthy and infertile men","volume":"100","author":"Hou","year":"2013","journal-title":"Fertil Steril"},{"key":"R38-20260309","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1111\/andr.12886","article-title":"The semen microbiome and its impact on sperm function and male fertility:a systematic review and meta-analysis","volume":"9","author":"Farahani","year":"2021","journal-title":"Andrology"},{"key":"R39-20260309","doi-asserted-by":"crossref","first-page":"103183","DOI":"10.1016\/j.jri.2020.103183","article-title":"Bacterial infection of the male reproductive system causing infertility","volume":"142","author":"Farsimadan","year":"2020","journal-title":"J Reprod Immunol"},{"key":"R40-20260309","doi-asserted-by":"crossref","first-page":"e13126","DOI":"10.1111\/aji.13126","article-title":"Chronic epididymitis and leptin and their associations with semen characteristics in men with infertility","volume":"82","author":"Xin","year":"2019","journal-title":"Am J Reprod Immunol"},{"key":"R41-20260309","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.theriogenology.2020.09.028","article-title":"Roles of host genetics and sperm microbiota in reproductive success in healthy rabbit","volume":"158","author":"Marco-Jim\u00e9nez","year":"2020","journal-title":"Theriogenology"}],"container-title":["Asian Journal of Andrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/aja202549","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T13:24:39Z","timestamp":1787837079000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/aja202549"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,12]]},"references-count":41,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026]]}},"URL":"https:\/\/doi.org\/10.4103\/aja202549","relation":{},"ISSN":["1745-7262","1008-682X"],"issn-type":[{"value":"1745-7262","type":"print"},{"value":"1008-682X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,12]]},"assertion":[{"value":"2024-11-16","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-12","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}