{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T00:27:02Z","timestamp":1760488022386,"version":"build-2065373602"},"reference-count":87,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:00:00Z","timestamp":1760313600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"2024 Jilin Provincial Budgetary Capital Construction Funds","award":["2024C014-5"],"award-info":[{"award-number":["2024C014-5"]}]},{"name":"Jilin Agriculture Research System of Sika deer","award":["JLARS-2025-080204"],"award-info":[{"award-number":["JLARS-2025-080204"]}]},{"name":"Agricultural Science and Technology Innovation Program of Chinese Academy of Agricultural Sciences","award":["CAAS-ASTIP-2021-ISAPS"],"award-info":[{"award-number":["CAAS-ASTIP-2021-ISAPS"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>With estrus confined to three winter months, early pregnancy detection is essential for reproductive management in farmed sika deer. However, the development of reliable non-invasive early pregnancy detection techniques has been hindered by limited understanding of their reproductive physiology. To identify pregnancy-specific biomarkers in sika deer, we performed RNA-sequencing (RNA-Seq) on maternal peripheral blood collected on days 0, 7, 15, and 20 after artificial insemination. Using time-series clustering analysis and weighted gene co-expression network analysis (WGCNA), we identified key genes and pathways at each stage. Notably, maternal-fetal recognition-related interferon-stimulated genes (ISGs; IFNAR1\/2, STAT1\/2, MX1\/2, and RSAD2), anti-apoptotic and immune-regulatory genes (BCL2, XIAP, and IL10), and cysteine metabolism genes (CTH, CBS, GCLC, and GCLM) were upregulated by day 7, suggesting their role in supporting corpus luteum development through immune regulation and redox homeostasis. By days 15\u201320, upregulated genes were enriched in pathways related to mitochondrial function, cell adhesion, and cell cycle regulation, indicating their involvement in embryo adhesion and syndesmochorial placentation. In conclusion, this study demonstrates that ISGs, immune-regulatory genes and cysteine metabolism genes are detectable as early as day 7 post-insemination, highlighting their promise as early pregnancy biomarkers and providing a molecular basis for non-invasive diagnostic development in sika deer.<\/jats:p>","DOI":"10.3390\/ani15202960","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T07:51:28Z","timestamp":1760428288000},"page":"2960","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Transcriptomic Profiling of Peripheral Blood Identifies Candidate Genes for Early Pregnancy Diagnosis in Sika Deer"],"prefix":"10.3390","volume":"15","author":[{"given":"Yushi","family":"Zhang","sequence":"first","affiliation":[{"name":"Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun 130112, China"},{"name":"State Key Laboratory for Molecular Biology of Special Economic Animals, Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun 130112, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huimin","family":"Sun","sequence":"additional","affiliation":[{"name":"Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun 130112, China"},{"name":"State Key Laboratory for Molecular Biology of Special Economic Animals, Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun 130112, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bingfeng","family":"Fan","sequence":"additional","affiliation":[{"name":"Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun 130112, China"},{"name":"State Key Laboratory for Molecular Biology of Special Economic Animals, Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun 130112, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lixiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun 130112, China"},{"name":"State Key Laboratory for Molecular Biology of Special Economic Animals, Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun 130112, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Tang","sequence":"additional","affiliation":[{"name":"Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun 130112, China"},{"name":"State Key Laboratory for Molecular Biology of Special Economic Animals, Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun 130112, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun 130112, China"},{"name":"State Key Laboratory for Molecular Biology of Special Economic Animals, Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun 130112, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xulin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun 130112, China"},{"name":"State Key Laboratory for Molecular Biology of Special Economic Animals, Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun 130112, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyu","family":"Chu","sequence":"additional","affiliation":[{"name":"Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun 130112, China"},{"name":"State Key Laboratory for Molecular Biology of Special Economic Animals, Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun 130112, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feiyu","family":"Peng","sequence":"additional","affiliation":[{"name":"Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun 130112, China"},{"name":"State Key Laboratory for Molecular Biology of Special Economic Animals, Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun 130112, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Cao","sequence":"additional","affiliation":[{"name":"Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun 130112, China"},{"name":"State Key Laboratory for Molecular Biology of Special Economic Animals, Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun 130112, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baozeng","family":"Xu","sequence":"additional","affiliation":[{"name":"Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun 130112, China"},{"name":"State Key Laboratory for Molecular Biology of Special Economic Animals, Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun 130112, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Liu, L., Jiao, Y., Yang, M., Wu, L., Long, G., and Hu, W. (2023). Network Pharmacology, Molecular Docking and Molecular Dynamics to Explore the Potential Immunomodulatory Mechanisms of Deer Antler. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241210370"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.theriogenology.2013.10.011","article-title":"Evidence of higher levels of testosterone during the velvet period in muntjac than in other cervids","volume":"81","author":"Lin","year":"2014","journal-title":"Theriogenology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.anireprosci.2010.08.026","article-title":"Reproductive cycles of deer","volume":"124","author":"Asher","year":"2011","journal-title":"Anim. Reprod. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"275","DOI":"10.3106\/041.038.0402","article-title":"Temporal pattern of estrus in free-ranging sika deer (Cervus nippon)","volume":"38","author":"Higuchi","year":"2013","journal-title":"Mammal. Study"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"skac123","DOI":"10.1093\/jas\/skac123","article-title":"Ruminant conceptus-maternal interactions: Interferon-tau and beyond","volume":"100","author":"Mathew","year":"2022","journal-title":"J. Anim. Sci."},{"key":"ref_6","first-page":"136","article-title":"Assisted reproductive technologies in deer (Artiodactyla, Cervidae): A review","volume":"45","author":"Pintus","year":"2014","journal-title":"Sci. Agric. Bohem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1017\/S1751731119002775","article-title":"Review: Recent advances in bovine in vitro embryo production: Reproductive biotechnology history and methods","volume":"14","author":"Kjelland","year":"2020","journal-title":"Animal"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"9236","DOI":"10.3168\/jds.2019-16515","article-title":"Effect of student transrectal palpation on early pregnancy loss in dairy cattle","volume":"102","author":"Bond","year":"2019","journal-title":"J. Dairy Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.theriogenology.2024.05.006","article-title":"Accuracy of early pregnancy diagnosis and determining pregnancy loss using different biomarkers and machine learning applications in dairy cattle","volume":"224","author":"Ferraz","year":"2024","journal-title":"Theriogenology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.theriogenology.2024.11.007","article-title":"Perspectives in cattle reproduction for the next 20 years\u2014A European context","volume":"233","author":"Pascottini","year":"2025","journal-title":"Theriogenology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1262\/jrd.2014-076","article-title":"Accessory corpora lutea formation in pregnant Hokkaido sika deer (Cervus nippon yesoensis) investigated by examination of ovarian dynamics and steroid hormone concentrations","volume":"61","author":"Yanagawa","year":"2015","journal-title":"J. Reprod. Dev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.theriogenology.2022.01.002","article-title":"Early pregnancy diagnosis based on luteal morphology and blood flow on Days 17-21 post-artificial insemination in Japanese Black cattle","volume":"181","author":"Kanazawa","year":"2022","journal-title":"Theriogenology"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Shin, H., Shannon, C.P., Fishbane, N., Ruan, J., Zhou, M., Balshaw, R., Wilson-McManus, J.E., Ng, R.T., McManus, B.M., and Tebbutt, S.J. (2014). Variation in RNA-Seq transcriptome profiles of peripheral whole blood from healthy individuals with and without globin depletion. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0091041"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Poscic, N., Montanari, T., D\u2019Andrea, M., Licastro, D., Pilla, F., Ajmone-Marsan, P., Minuti, A., and Sgorlon, S. (2017). Breed and adaptive response modulate bovine peripheral blood cells\u2019 transcriptome. J. Anim. Sci. Biotechnol., 8.","DOI":"10.1186\/s40104-017-0143-y"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Rocha, C.C., da Silva Andrade, S.C., de Melo, G.D., Motta, I.G., Coutinho, L.L., Gonella-Diaza, A.M., Binelli, M., and Pugliesi, G. (2020). Early pregnancy-induced transcripts in peripheral blood immune cells in Bos indicus heifers. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-70616-8"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3080","DOI":"10.3168\/jds.2023-24199","article-title":"Early transcriptomic changes in peripheral blood 7 days after embryo transfer in dairy cattle","volume":"107","author":"Strangstalien","year":"2024","journal-title":"J. Dairy Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"100796","DOI":"10.1016\/j.animal.2023.100796","article-title":"Review: Implantation and placentation in ruminants","volume":"17","author":"Davenport","year":"2023","journal-title":"Animal"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"F45","DOI":"10.1530\/REP-17-0315","article-title":"Paracrine and endocrine actions of interferon tau (IFNT)","volume":"154","author":"Hansen","year":"2017","journal-title":"Reproduction"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1152\/physiolgenomics.00082.2013","article-title":"Pregnancy-associated genes contribute to antiluteolytic mechanisms in ovine corpus luteum","volume":"45","author":"Romero","year":"2013","journal-title":"Physiol. Genom."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"100827","DOI":"10.1016\/j.animal.2023.100827","article-title":"Review: Maintenance of the ruminant corpus luteum during pregnancy: Interferon-tau and beyond","volume":"17","author":"Wiltbank","year":"2023","journal-title":"Animal"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3766","DOI":"10.3168\/jds.2018-15668","article-title":"Symposium review: Immunological detection of the bovine conceptus during early pregnancy","volume":"102","author":"Ott","year":"2019","journal-title":"J. Dairy Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e2221526120","DOI":"10.1073\/pnas.2221526120","article-title":"Single-nuclei RNA sequencing (snRNA-seq) uncovers trophoblast cell types and lineages in the mature bovine placenta","volume":"120","author":"Davenport","year":"2023","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1093\/biolre\/ioac107","article-title":"The ruminant placental trophoblast binucleate cell: An evolutionary breakthrough","volume":"107","author":"Wooding","year":"2022","journal-title":"Biol. Reprod."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1002\/aja.1001700208","article-title":"Role of binucleate cells in fetomaternal cell fusion at implantation in the sheep","volume":"170","author":"Wooding","year":"1984","journal-title":"Am. J. Anat."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/978-3-319-15856-3_7","article-title":"Implantation and Establishment of Pregnancy in Ruminants","volume":"216","author":"Spencer","year":"2015","journal-title":"Adv. Anat. Embryol. Cell Biol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Lee, J.H., Oh, M.G., and Kim, S.H. (2022). Reconstitution of Caruncle Placenta through the 20alpha-HSD\/Casp-3 Apoptotic Pathway during Early Pregnancy in Bovines. Cells, 12.","DOI":"10.3390\/cells12010162"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.jri.2010.01.008","article-title":"Immune regulation of conception and embryo implantation-all about quality control?","volume":"85","author":"Robertson","year":"2010","journal-title":"J. Reprod. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/S0002-9378(98)70254-6","article-title":"Normal pregnancy and preeclampsia both produce inflammatory changes in peripheral blood leukocytes akin to those of sepsis","volume":"179","author":"Sacks","year":"1998","journal-title":"Am. J. Obs. Gynecol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1038\/nri1897","article-title":"Immunology of placentation in eutherian mammals","volume":"6","author":"Moffett","year":"2006","journal-title":"Nat. Rev. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1007\/s00011-022-01569-z","article-title":"Pregnancy tailors endotoxin-induced monocyte and neutrophil responses in the maternal circulation","volume":"71","author":"Romero","year":"2022","journal-title":"Inflamm. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.anireprosci.2006.10.008","article-title":"The role of oxygen in ruminant preimplantation embryo development and metabolism","volume":"98","author":"Harvey","year":"2007","journal-title":"Anim. Reprod. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"F95","DOI":"10.1530\/REP-22-0121","article-title":"OXIDATIVE STRESS AND REPRODUCTIVE FUNCTION: Reactive oxygen species in the mammalian pre-implantation embryo","volume":"164","author":"Deluao","year":"2022","journal-title":"Reproduction"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Herb, M., and Schramm, M. (2021). Functions of ROS in Macrophages and Antimicrobial Immunity. Antioxidants, 10.","DOI":"10.3390\/antiox10020313"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Sun, L., Wang, X., Saredy, J., Yuan, Z., Yang, X., and Wang, H. (2020). Innate-adaptive immunity interplay and redox regulation in immune response. Redox Biol., 37.","DOI":"10.1016\/j.redox.2020.101759"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1067\/mob.2001.117682","article-title":"Phenotypic and metabolic characteristics of monocytes and granulocytes in normal pregnancy and maternal infection","volume":"185","author":"Naccasha","year":"2001","journal-title":"Am. J. Obs. Gynecol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Abu-Raya, B., Michalski, C., Sadarangani, M., and Lavoie, P.M. (2020). Maternal Immunological Adaptation During Normal Pregnancy. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.575197"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Gusar, V.A., Timofeeva, A.V., Chagovets, V.V., Vysokikh, M.Y., Kan, N.E., Manukhova, L.A., Marey, M.V., and Sukhikh, G.T. (2022). Interrelation between miRNAs Expression Associated with Redox State Fluctuations, Immune and Inflammatory Response Activation, and Neonatal Outcomes in Complicated Pregnancy, Accompanied by Placental Insufficiency. Antioxidants, 12.","DOI":"10.3390\/antiox12010006"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/s10735-024-10332-z","article-title":"Oxidative stress and its role in recurrent pregnancy loss: Mechanisms and implications","volume":"56","author":"Zhang","year":"2024","journal-title":"J. Mol. Histol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1262\/jrd.50.215","article-title":"Withdrawal of ovarian steroids stimulates prostaglandin F2alpha production through nuclear factor-kappaB activation via oxygen radicals in human endometrial stromal cells: Potential relevance to menstruation","volume":"50","author":"Sugino","year":"2004","journal-title":"J. Reprod. Dev."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Agarwal, A., Gupta, S., and Sharma, R.K. (2005). Role of oxidative stress in female reproduction. Reprod. Biol. Endocrinol., 3.","DOI":"10.1186\/1477-7827-3-28"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.rbmo.2012.08.004","article-title":"Roles of antioxidant enzymes in corpus luteum rescue from reactive oxygen species-induced oxidative stress","volume":"25","author":"Garrel","year":"2012","journal-title":"Reprod. Biomed. Online"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Ufer, C., and Wang, C.C. (2011). The Roles of Glutathione Peroxidases during Embryo Development. Front. Mol. Neurosci., 4.","DOI":"10.3389\/fnmol.2011.00012"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Chen, T.H., Wang, H.C., Chang, C.J., and Lee, S.Y. (2024). Mitochondrial Glutathione in Cellular Redox Homeostasis and Disease Manifestation. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25021314"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: A flexible trimmer for Illumina sequence data","volume":"30","author":"Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nmeth.3317","article-title":"HISAT: A fast spliced aligner with low memory requirements","volume":"12","author":"Kim","year":"2015","journal-title":"Nat. Methods"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2184","DOI":"10.1093\/bioinformatics\/bts356","article-title":"RSeQC: Quality control of RNA-seq experiments","volume":"28","author":"Wang","year":"2012","journal-title":"Bioinformatics"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1038\/nprot.2016.095","article-title":"Transcript-level expression analysis of RNA-seq experiments with HISAT, StringTie and Ballgown","volume":"11","author":"Pertea","year":"2016","journal-title":"Nat. Protoc."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1261\/rna.074922.120","article-title":"Misuse of RPKM or TPM normalization when comparing across samples and sequencing protocols","volume":"26","author":"Zhao","year":"2020","journal-title":"RNA"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1038\/nbt0308-303","article-title":"What is principal component analysis?","volume":"26","author":"Ringner","year":"2008","journal-title":"Nat. Biotechnol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"5","DOI":"10.6026\/97320630002005","article-title":"Mfuzz: A software package for soft clustering of microarray data","volume":"2","author":"Kumar","year":"2007","journal-title":"Bioinformation"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Langfelder, P., and Horvath, S. (2008). WGCNA: An R package for weighted correlation network analysis. BMC Bioinform., 9.","DOI":"10.1186\/1471-2105-9-559"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"11728","DOI":"10.3168\/jds.2024-25063","article-title":"Effects of parity and early pregnancy on peripheral blood leukocytes in dairy cattle","volume":"107","author":"Oli","year":"2024","journal-title":"J. Dairy Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.anireprosci.2010.05.010","article-title":"Measurement of interferon-tau (IFN-tau) stimulated gene expression in blood leukocytes for pregnancy diagnosis within 18-20d after insemination in dairy cattle","volume":"121","author":"Green","year":"2010","journal-title":"Anim. Reprod. Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"274","DOI":"10.3168\/jds.S0022-0302(07)72628-0","article-title":"Regulation of interferon-stimulated genes in peripheral blood leukocytes in pregnant and bred, nonpregnant dairy cows","volume":"90","author":"Gifford","year":"2007","journal-title":"J. Dairy Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1856","DOI":"10.1017\/S175173111600077X","article-title":"Interferon stimulated genes as peripheral diagnostic markers of early pregnancy in sheep: A critical assessment","volume":"10","author":"Mauffre","year":"2016","journal-title":"Animal"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1095\/biolreprod.109.079467","article-title":"Uterine vein infusion of interferon tau (IFNT) extends luteal life span in ewes","volume":"82","author":"Bott","year":"2010","journal-title":"Biol. Reprod."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Romero, J.J., Antoniazzi, A.Q., Nett, T.M., Ashley, R.L., Webb, B.T., Smirnova, N.P., Bott, R.C., Bruemmer, J.E., Bazer, F.W., and Anthony, R.V. (2015). Temporal Release, Paracrine and Endocrine Actions of Ovine Conceptus-Derived Interferon-Tau During Early Pregnancy. Biol. Reprod., 93.","DOI":"10.1095\/biolreprod.115.132860"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1038\/s41392-023-01468-7","article-title":"Evolving cognition of the JAK-STAT signaling pathway: Autoimmune disorders and cancer","volume":"8","author":"Xue","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1111\/rda.12700","article-title":"Serum MX2 Protein as Candidate Biomarker for Early Pregnancy Diagnosis in Buffalo","volume":"51","author":"Buragohain","year":"2016","journal-title":"Reprod. Domest. Anim."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1111\/aji.12097","article-title":"Adaptive immune responses during pregnancy","volume":"69","author":"Zenclussen","year":"2013","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.imlet.2014.06.013","article-title":"The immunology of pregnancy: Regulatory T cells control maternal immune tolerance toward the fetus","volume":"162","author":"Carbone","year":"2014","journal-title":"Immunol. Lett."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1111\/aji.12075","article-title":"Minor histocompatibility antigens and the maternal immune response to the fetus during pregnancy","volume":"69","author":"Linscheid","year":"2013","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.trsl.2024.09.004","article-title":"Spatial proteomics and transcriptomics of the maternal-fetal interface in placenta accreta spectrum","volume":"274","author":"Bartels","year":"2024","journal-title":"Transl. Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1530\/REP-15-0302","article-title":"Early pregnancy modulates survival and apoptosis pathways in the corpus luteum in sheep","volume":"151","author":"Lee","year":"2016","journal-title":"Reproduction"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1177\/1076029613494467","article-title":"Inflammatory and procoagulant cytokine levels during pregnancy as predictors of adverse obstetrical complications","volume":"20","author":"Dibble","year":"2014","journal-title":"Clin. Appl. Thromb. Hemost."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"103750","DOI":"10.1016\/j.jri.2022.103750","article-title":"IL-10: A bridge between immune cells and metabolism during pregnancy","volume":"154","author":"Wang","year":"2022","journal-title":"J. Reprod. Immunol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1111\/bph.14446","article-title":"Regulators of the transsulfuration pathway","volume":"176","author":"Sbodio","year":"2019","journal-title":"Br. J. Pharmacol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"102066","DOI":"10.1016\/j.arr.2023.102066","article-title":"Glutathione and glutathione-dependent enzymes: From biochemistry to gerontology and successful aging","volume":"92","author":"Lapenna","year":"2023","journal-title":"Ageing Res. Rev."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.biochi.2016.01.001","article-title":"Thioethers as markers of hydrogen sulfide production in homocystinurias","volume":"126","author":"Kozich","year":"2016","journal-title":"Biochimie"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Katsouda, A., Markou, M., Zampas, P., Varela, A., Davos, C.H., Vellecco, V., Cirino, G., Bucci, M., and Papapetropoulos, A. (2023). CTH\/MPST double ablation results in enhanced vasorelaxation and reduced blood pressure via upregulation of the eNOS\/sGC pathway. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1090654"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1093\/biolre\/ioz027","article-title":"Ovine uterine artery hydrogen sulfide biosynthesis in vivo: Effects of ovarian cycle and pregnancydagger","volume":"100","author":"Lechuga","year":"2019","journal-title":"Biol. Reprod."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"e4275","DOI":"10.1210\/clinem\/dgaa357","article-title":"Trophoblast H2S Maintains Early Pregnancy via Regulating Maternal-Fetal Interface Immune Hemostasis","volume":"105","author":"Wang","year":"2020","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Feng, H., Tian, C., Jiang, W., Sun, Z., Li, Y., Han, B., Chen, L., Wang, D., Xiang, H., and Zhu, J. (2025). Hydrogen sulfide sustains mitochondria functions via targeting mitochondria fission regulator 1 like protein to restore human cytotrophoblast invasion and migration. Int. J. Biol. Macromol., 299.","DOI":"10.1016\/j.ijbiomac.2025.140240"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1038\/s41419-024-07167-7","article-title":"Miro2 sulfhydration by CBS\/H(2)S promotes human trophoblast invasion and migration via regulating mitochondria dynamics","volume":"15","author":"Feng","year":"2024","journal-title":"Cell Death Dis."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1093\/humupd\/dmad016","article-title":"The pathophysiological role of estrogens in the initial stages of pregnancy: Molecular mechanisms and clinical implications for pregnancy outcome from the periconceptional period to end of the first trimester","volume":"29","author":"Parisi","year":"2023","journal-title":"Hum. Reprod. Update"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Deng, W., Sun, R., Du, J., Wu, X., Ma, L., Wang, M., and Lv, Q. (2022). Prediction of miscarriage in first trimester by serum estradiol, progesterone and beta-human chorionic gonadotropin within 9 weeks of gestation. BMC Pregnancy Childbirth, 22.","DOI":"10.1186\/s12884-021-04158-w"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Wang, Y., Tang, Z., and Teng, X. (2024). New advances in the treatment of thin endometrium. Front. Endocrinol., 15.","DOI":"10.3389\/fendo.2024.1269382"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1002\/rmb2.12334","article-title":"Intrauterine administration of platelet-rich plasma improves embryo implantation by increasing the endometrial thickness in women with repeated implantation failure: A single-arm self-controlled trial","volume":"19","author":"Kusumi","year":"2020","journal-title":"Reprod. Med. Biol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.yfrne.2013.08.001","article-title":"Estrogen: A master regulator of bioenergetic systems in the brain and body","volume":"35","author":"Rettberg","year":"2014","journal-title":"Front. Neuroendocr."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Klinge, C.M. (2020). Estrogenic control of mitochondrial function. Redox Biol., 31.","DOI":"10.1016\/j.redox.2020.101435"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Sreerangaraja Urs, D.B., Wu, W.H., Komrskova, K., Postlerova, P., Lin, Y.F., Tzeng, C.R., and Kao, S.H. (2020). Mitochondrial Function in Modulating Human Granulosa Cell Steroidogenesis and Female Fertility. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21103592"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"119147","DOI":"10.1016\/j.gep.2020.119147","article-title":"Expression analysis of mammalian mitochondrial ribosomal protein genes","volume":"38","author":"Cheong","year":"2020","journal-title":"Gene Expr. Patterns"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1083\/jcb.200211046","article-title":"Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development","volume":"160","author":"Chen","year":"2003","journal-title":"J. Cell Biol."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Liao, M.H., Liu, X., Yu, X.T., Zhang, S., Li, Y.Z., Hu, L.L., Sun, S.C., and Wang, J.L. (2025). NAMPT regulates mitochondria and oxidative stress level for mouse early embryo development. Biol. Res., 58.","DOI":"10.1186\/s40659-025-00608-3"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"7216","DOI":"10.7150\/thno.78467","article-title":"Decorin promotes decidual M1-like macrophage polarization via mitochondrial dysfunction resulting in recurrent pregnancy loss","volume":"12","author":"Wang","year":"2022","journal-title":"Theranostics"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2338","DOI":"10.1016\/j.ygeno.2021.05.018","article-title":"Profiling and integrated analysis of whole-transcriptome changes in uterine caruncles of pregnant and non-pregnant buffaloes","volume":"113","author":"Murugesan","year":"2021","journal-title":"Genomics"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s12014-016-9116-y","article-title":"Identification of potential protein biomarkers for early detection of pregnancy in cow urine using 2D DIGE and label free quantitation","volume":"13","author":"Rawat","year":"2016","journal-title":"Clin. Proteom."}],"container-title":["Animals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2615\/15\/20\/2960\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T08:18:01Z","timestamp":1760429881000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2615\/15\/20\/2960"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,13]]},"references-count":87,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["ani15202960"],"URL":"https:\/\/doi.org\/10.3390\/ani15202960","relation":{},"ISSN":["2076-2615"],"issn-type":[{"value":"2076-2615","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,13]]}}}