{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T17:14:16Z","timestamp":1771002856282,"version":"3.50.1"},"reference-count":45,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T00:00:00Z","timestamp":1770940800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Agricultural Science and Technology Innovation Program of China","award":["CAAS-ZDRW202502"],"award-info":[{"award-number":["CAAS-ZDRW202502"]}]},{"name":"Central Public-interest Scientific Institution Basal Research Fund","award":["Y2024YJ08"],"award-info":[{"award-number":["Y2024YJ08"]}]},{"name":"2024 Key research projects in seed industry and agricultural science and technology support projects of Gansu","award":["GYGG-2024-6"],"award-info":[{"award-number":["GYGG-2024-6"]}]},{"name":"earmarked fund for Gansu Agriculture Research System","award":["GSARS02"],"award-info":[{"award-number":["GSARS02"]}]},{"name":"Central Public-interest Scientific Institution Basal Research Fund","award":["1610322023015"],"award-info":[{"award-number":["1610322023015"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>Objective: Although Hu sheep are renowned for their high fecundity, the multi-tissue regulatory networks governing spermatogenesis, particularly within the hypothalamic\u2013pituitary\u2013testicular (HPT) axis, remain poorly understood. This study aimed to elucidate these mechanisms by performing a comparative proteomic analysis of the HPT axis in Hu sheep and three other breeds. Methods: We utilized data-independent acquisition (DIA) proteomics to analyze hypothalamic, pituitary, and testis tissues from 36 samples across four breeds. The experimental workflow included protein extraction, enzymatic digestion, LC-MS\/MS, and subsequent bioinformatic analyses, complemented by histological examination. Results: Hu sheep exhibited accelerated testicular development and an earlier onset of spermatogenesis. Comprehensive proteomic profiling identified a total of 10,528 proteins, with 771 differentially expressed proteins (DEPs) detected in the testis. These testicular DEPs were significantly enriched in pathways related to spermatogenesis, the blood\u2013testis barrier, and steroid hormone biosynthesis. Notably, the cAMP signaling pathway was consistently enriched across all three tissues, underscoring its pivotal role in regulating spermatogenesis. Protein\u2013protein interaction (PPI) network analysis further highlighted hub proteins, such as MET, suggesting their potential involvement in somatic cell functions and the spermatogenic microenvironment. Key findings were validated by Western blot analysis. Conclusion: This study is the first multi-tissue proteomic investigation proposing a model in which the high reproductive performance of Hu sheep is potentially linked to the efficient, coordinated regulation of spermatogenesis-related proteins and signaling pathways\u2014particularly in the testis. These findings offer novel insights into the molecular mechanisms of male reproduction in sheep and identify potential targets for future research and breeding applications.<\/jats:p>","DOI":"10.3390\/ani16040595","type":"journal-article","created":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T16:09:32Z","timestamp":1770998972000},"page":"595","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["DIA Proteomics Reveals the Mechanism of cAMP Signaling Pathway-Mediated HPT Axis in Regulating Spermatogenesis of Hu Sheep"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-4211-7482","authenticated-orcid":false,"given":"Lina","family":"Zhu","sequence":"first","affiliation":[{"name":"Key Laboratory of Animal Genetics and Breeding on the Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China"},{"name":"Sheep Breeding Engineering Technology Research Center of Chinese Academy of Agricultural Sciences, Lanzhou 730050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6860-4587","authenticated-orcid":false,"given":"Shujun","family":"Shi","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Genetics and Breeding on the Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China"},{"name":"Sheep Breeding Engineering Technology Research Center of Chinese Academy of Agricultural Sciences, Lanzhou 730050, China"},{"name":"College of Life Science and Engineering, Northwest Minzu University, Lanzhou 730050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0605-6502","authenticated-orcid":false,"given":"Qiao","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Genetics and Breeding on the Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China"},{"name":"Sheep Breeding Engineering Technology Research Center of Chinese Academy of Agricultural Sciences, Lanzhou 730050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6708-8850","authenticated-orcid":false,"given":"Rui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Genetics and Breeding on the Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China"},{"name":"Sheep Breeding Engineering Technology Research Center of Chinese Academy of Agricultural Sciences, Lanzhou 730050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2168-5072","authenticated-orcid":false,"given":"Haifeng","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Genetics and Breeding on the Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China"},{"name":"Sheep Breeding Engineering Technology Research Center of Chinese Academy of Agricultural Sciences, Lanzhou 730050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4191-2885","authenticated-orcid":false,"given":"Zhenghan","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Genetics and Breeding on the Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China"},{"name":"Sheep Breeding Engineering Technology Research Center of Chinese Academy of Agricultural Sciences, Lanzhou 730050, China"},{"name":"Shaanxi Provincial Engineering and Technology Research Center of Cashmere Goats, Life Science Research Center, Yulin University, Yulin 719000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6178-9359","authenticated-orcid":false,"given":"Binpeng","family":"Xi","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Genetics and Breeding on the Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China"},{"name":"Sheep Breeding Engineering Technology Research Center of Chinese Academy of Agricultural Sciences, Lanzhou 730050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1381-2724","authenticated-orcid":false,"given":"Xuejiao","family":"An","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Genetics and Breeding on the Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China"},{"name":"Sheep Breeding Engineering Technology Research Center of Chinese Academy of Agricultural Sciences, Lanzhou 730050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4473-9710","authenticated-orcid":false,"given":"Yaojing","family":"Yue","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Genetics and Breeding on the Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China"},{"name":"Sheep Breeding Engineering Technology Research Center of Chinese Academy of Agricultural Sciences, Lanzhou 730050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.omtn.2021.02.030","article-title":"lncRNA FDNCR promotes apoptosis of granulosa cells by targeting the miR-543-3p\/DCN\/TGF-\u03b2 signaling pathway in Hu sheep","volume":"24","author":"Yao","year":"2021","journal-title":"Mol. 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