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Here, to explore the expression pattern of multi-tissue genes in Chinese native sheep, we selected 10 tissues of the three adult ewes with the highest estimated breeding value in the early study of the prolific Xinggao sheep population. The global gene expression analysis showed that the ovary, uterus, and hypothalamus expressed the most genes. Using the Uniform Manifold Approximation and Projection (UMAP) cluster analysis, these samples were clustered into eight clusters. The functional enrichment analysis showed that the genes expressed in the spleen, uterus, and ovary were significantly enriched in the Ataxia Telangiectasia Mutated Protein (ATM) signaling pathway, and most genes in the liver, spleen, and ovary were enriched in the immune response pathway. Moreover, we focus on the expression genes of the hypothalamic\u2013pituitary\u2013ovarian axis (HPO) and found that 11,016 genes were co-expressed in the three tissues, and different tissues have different functions, but the oxytocin signaling pathway was widely enriched. To further explore the differences in the expression genes (DEGs) of HPO in different sheep breeds, we downloaded the transcriptome data in the public data, and the analysis of DEGs (Xinggao sheep vs. Sunite sheep in Hypothalamus, Xinggao sheep vs. Sunite sheep in Pituitary, and Xinggao sheep vs. Suffolk sheep in Ovary) revealed the neuroactive ligand\u2013receptor interactions. In addition, the gene subsets of the transcription factors (TFs) of DEGs were identified. The results suggest that 51 TF genes and the homeobox TF may play an important role in transcriptional variation across the HPO. Altogether, our study provided the first fundamental resource to investigate the physiological functions and regulation mechanisms in sheep. This important data contributes to improving our understanding of the reproductive biology of sheep and isolating effecting molecular markers that can be used for genetic selection in sheep.<\/jats:p>","DOI":"10.3390\/genes14101881","type":"journal-article","created":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T01:42:12Z","timestamp":1695865332000},"page":"1881","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Integrated Multi-Tissue Transcriptome Profiling Characterizes the Genetic Basis and Biomarkers Affecting Reproduction in Sheep (Ovis aries)"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5093-9193","authenticated-orcid":false,"given":"Zaixia","family":"Liu","sequence":"first","affiliation":[{"name":"College of Animal Science, Inner Mongolia Agricultural University, Hohhot 010018, China"},{"name":"Inner Mongolia Engineering Research Center of Genomic Big Data for Agriculture, Hohhot 010018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoyin","family":"Fu","sequence":"additional","affiliation":[{"name":"Institute of Animal Husbandry, Inner Mongolia Academy of Agricultural and Animal Husbandry Sciences, Hohhot 010031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolong","family":"He","sequence":"additional","affiliation":[{"name":"Institute of Animal Husbandry, Inner Mongolia Academy of Agricultural and Animal Husbandry Sciences, Hohhot 010031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingli","family":"Dai","sequence":"additional","affiliation":[{"name":"College of Animal Science, Inner Mongolia Agricultural University, Hohhot 010018, China"},{"name":"Inner Mongolia Engineering Research Center of Genomic Big Data for Agriculture, Hohhot 010018, China"},{"name":"Veterinary Research Institute, Inner Mongolia Academy of Agricultural and Animal Husbandry Sciences, Hohhot 010031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuewen","family":"Liu","sequence":"additional","affiliation":[{"name":"Animal Husbandry and Bioengineering, College of Agronomy, Xing\u2019an Vocational and Technical College, Ulanhot 137400, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Narisu","sequence":"additional","affiliation":[{"name":"College of Animal Science, Inner Mongolia Agricultural University, Hohhot 010018, China"},{"name":"Inner Mongolia Engineering Research Center of Genomic Big Data for Agriculture, Hohhot 010018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caixia","family":"Shi","sequence":"additional","affiliation":[{"name":"College of Animal Science, Inner Mongolia Agricultural University, Hohhot 010018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingjuan","family":"Gu","sequence":"additional","affiliation":[{"name":"College of Animal Science, Inner Mongolia Agricultural University, Hohhot 010018, China"},{"name":"Inner Mongolia Engineering Research Center of Genomic Big Data for Agriculture, Hohhot 010018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot 010018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Manda","sequence":"additional","affiliation":[{"name":"College of Animal Science, Inner Mongolia Agricultural University, Hohhot 010018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Guo","sequence":"additional","affiliation":[{"name":"College of Animal Science, Inner Mongolia Agricultural University, Hohhot 010018, China"},{"name":"Inner Mongolia Engineering Research Center of Genomic Big Data for Agriculture, Hohhot 010018, China"},{"name":"School of Life Science, Inner Mongolia University, Hohhot 010021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanchun","family":"Bao","sequence":"additional","affiliation":[{"name":"College of Animal Science, Inner Mongolia Agricultural University, Hohhot 010018, China"},{"name":"Inner Mongolia Engineering Research Center of Genomic Big Data for Agriculture, Hohhot 010018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Baiyinbatu","sequence":"additional","affiliation":[{"name":"College of Animal Science, Inner Mongolia Agricultural University, Hohhot 010018, China"},{"name":"Inner Mongolia Engineering Research Center of Genomic Big Data for Agriculture, Hohhot 010018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7146-2067","authenticated-orcid":false,"given":"Chencheng","family":"Chang","sequence":"additional","affiliation":[{"name":"College of Animal Science, Inner Mongolia Agricultural University, Hohhot 010018, 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