{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T21:22:49Z","timestamp":1788470569560,"version":"build-2803163510"},"reference-count":47,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T00:00:00Z","timestamp":1760659200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Chongqing Modern Agricultural Industry Technology System","award":["CQMAITS202513"],"award-info":[{"award-number":["CQMAITS202513"]}]},{"name":"Technological Innovation and Application Development Project of Chongqing","award":["cstc2021jscx-gksbX0012"],"award-info":[{"award-number":["cstc2021jscx-gksbX0012"]}]},{"name":"Chongqing University Innovation Research Group Project","award":["CXQT21008"],"award-info":[{"award-number":["CXQT21008"]}]},{"name":"Chongqing Natural Fund project","award":["cstc2020jcyj-msxmX0436"],"award-info":[{"award-number":["cstc2020jcyj-msxmX0436"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>This study investigated the metabolomic profiles and molecular basis of hybrid male sterility (HMS) in dzo (the male F1 hybrid offspring of taurine cattle (Bos taurus, \u2642) \u00d7 domestic yak (Bos grunniens, \u2640)). In total, 147 co-different metabolites were identified between liver and testis tissues. Metabolomics analysis linked testis-specific abnormal citrate cycle and phenylalanine metabolism to dzo male infertility. Specifically, \u03b1-ketoglutaric acid, L-malic acid, and succinic acid were specific elevated in dzo testes, but not significantly different in liver. The testis-specific metabolite phenyllactate was reduced in dzo. Moreover, genes encoding \u03b1-ketoglutarate-dependent oxygenases were dysregulated only in dzo testes, including histone demethylations and RNA m6A modifications. Reactive oxygen species and m6A content were significantly decreased in dzo testes. Multiomics data showed that testis-specific metabolic abnormalities in dzo were linked to upregulated IDH3A and IDH3G, and downregulated testis-specific OGDHL and PDHA2. MiRNA-15b targeting to IDH3A was downregulated in dzo testes. The promoter of PDHA2 was hypermethylated and showed lower chromatin accessibility in dzo testes. Notably, testis-specific LDHC downregulation was also associated with lower phenyllactate in dzo testes, which could be an outcome of male infertility. Overall, this study provides comprehensive insights into the citrate cycle as a key pathway associated with dzo sterility, shedding light on the potential mitochondrial\u2013nuclear incompatibility pertinent to addressing this HMS challenge.<\/jats:p>","DOI":"10.3390\/ani15203023","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T14:29:17Z","timestamp":1760711357000},"page":"3023","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Metabolomics Reveals Abnormal Citrate Cycle and Phenylalanine Metabolism in Testes from Infertile Hybrid Dzo"],"prefix":"10.3390","volume":"15","author":[{"given":"Jiaojiao","family":"Ding","sequence":"first","affiliation":[{"name":"College of Animal Science and Technology, Southwest University, Chongqing 402460, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Dao","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Southwest University, Chongqing 402460, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingqian","family":"Liang","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Southwest University, Chongqing 402460, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Hong","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Southwest University, Chongqing 402460, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiyou","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Southwest University, Chongqing 402460, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Yan","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Southwest University, Chongqing 402460, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Southwest University, Chongqing 402460, China"},{"name":"Beef Cattle Engineering and Technology Research Center of Chongqing, Southwest University, Chongqing 402460, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuyuan","family":"Zuo","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Southwest University, Chongqing 402460, China"},{"name":"Beef Cattle Engineering and Technology Research Center of Chongqing, Southwest University, Chongqing 402460, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gongwei","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Southwest University, Chongqing 402460, China"},{"name":"Beef Cattle Engineering and Technology Research Center of Chongqing, Southwest University, Chongqing 402460, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"113253","DOI":"10.1016\/j.foodres.2023.113253","article-title":"Quantitative proteomic analysis of cattle-yak and yak longissimus thoracis provides insights into the differential mechanisms of meat quality","volume":"173","author":"Chang","year":"2023","journal-title":"Food Res. 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