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Fermented Chinese chive (Allium tuberosum) is known for its antioxidant and immunomodulatory properties, yet its role in testicular development remains unclear. In this study, Songliao Black piglets received 3\u2030 fermented Chinese chive (LK group) mixed with starter feed and compared to a control (OD group). Testicular samples at weaning (28 days) underwent transcriptomic and metabolomic analyses. Although no significant differences were observed in gross testicular morphology, the LK group significantly increased individual (13.85%) and litter (15.11%) weaning weights (p &lt; 0.05), with elevated serum triglycerides, total cholesterol, and a 32.2% rise in IgG levels (p &lt; 0.05). Integrated analysis identified 76 shared pathways, including ferroptosis, insulin resistance, PI3K-Akt, MAPK, and cAMP signaling. Upregulated genes in the LK group were mainly related to energy metabolism, antioxidant defense, immune regulation, steroidogenesis, and neuroendocrine signaling, suggesting improved metabolic activity, reduced oxidative stress, and accelerated reproductive maturation. Molecular docking indicated that kaempferol and isorhamnetin from Chinese chive bind strongly to proteins involved in testicular development. Overall, fermented Chinese chive supplementation enhances early testicular development in suckling piglets via integrated modulation of metabolic, immune, and signaling pathways, providing a nutritional strategy to optimize reproductive potential in breeding boars.<\/jats:p>","DOI":"10.3390\/antiox14091056","type":"journal-article","created":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T15:03:14Z","timestamp":1756393394000},"page":"1056","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Integrated Transcriptomic and Metabolomic Analysis Reveals Regulatory Effects of Fermented Chinese Chive on Early Testicular Development in Piglets"],"prefix":"10.3390","volume":"14","author":[{"given":"Yupeng","family":"Xie","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, College of Animal Science and Technology, Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun 130118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5211-1872","authenticated-orcid":false,"given":"Suthar Teerath","family":"Kumar","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Key Laboratory of Animal Production, Product Quality and Security, Ministry of Education, Jilin Agricultural University, Changchun 130118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Zou","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, College of Animal Science and Technology, Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun 130118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting-Ting","family":"Luo","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, College of Animal Science and Technology, Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun 130118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunpeng","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Key Laboratory of Animal Production, Product Quality and Security, Ministry of Education, Jilin Agricultural University, Changchun 130118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7166-1484","authenticated-orcid":false,"given":"Qi","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Key Laboratory of Animal Production, Product Quality and Security, Ministry of Education, Jilin Agricultural University, Changchun 130118, China"},{"name":"Institute of Animal Husbandry and Veterinary, Jilin Academy of Agricultural Sciences, Changchun 136100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Li","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, College of Animal Science and Technology, Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun 130118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai-Min","family":"Niu","sequence":"additional","affiliation":[{"name":"Institute of Biological Resource, Jiangxi Academy of Sciences, Nanchang 330029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenya","family":"Zhai","sequence":"additional","affiliation":[{"name":"Institute of Biological Resource, Jiangxi Academy of Sciences, Nanchang 330029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunfeng","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, College of Animal Science and Technology, Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun 130118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wu-Sheng","family":"Sun","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, College of Animal Science and Technology, Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun 130118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-Min","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Key Laboratory of Animal Production, Product Quality and Security, Ministry of Education, Jilin Agricultural University, Changchun 130118, 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(2023). A review on the potential effects of environmental and economic factors on sheep genetic diversity: Consequences of climate change. Saudi J. Biol. Sci., 30.","DOI":"10.1016\/j.sjbs.2022.103505"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"117623","DOI":"10.1016\/j.ecoenv.2024.117623","article-title":"Detrimental effects of cadmium on male infertility: A review","volume":"290","year":"2025","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Xu, H., Sun, W., Pei, S., Li, W., Li, F., and Yue, X. (2021). Identification of Key Genes Related to Postnatal Testicular Development Based on Transcriptomic Data of Testis in Hu Sheep. Front. Genet., 12.","DOI":"10.3389\/fgene.2021.773695"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"116055","DOI":"10.1016\/j.jep.2022.116055","article-title":"Integration of metabolomics and transcriptomics to reveal ferroptosis is involved in Tripterygium wilfordii polyglycoside tablet-induced testicular injury","volume":"304","author":"Qin","year":"2023","journal-title":"J. Ethnopharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.fertnstert.2022.10.031","article-title":"A systematic review identifying fertility biomarkers in semen: A clinical approach through Omics to diagnose male infertility","volume":"119","year":"2023","journal-title":"Fertil. Steril."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Montano, L., Maugeri, A., Volpe, M.G., Micali, S., Mirone, V., Mantovani, A., Navarra, M., and Piscopo, M. (2022). Mediterranean Diet as a Shield against Male Infertility and Cancer Risk Induced by Environmental Pollutants: A Focus on Flavonoids. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23031568"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1071\/RD15325","article-title":"Causes and consequences of oxidative stress in spermatozoa","volume":"28","author":"Aitken","year":"2016","journal-title":"Reprod. Fertil. Dev."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Zhang, P., Zhang, F., Sui, H., Yang, X., Ji, Y., Zheng, S., Li, W., Cheng, K., Wang, C., and Jiao, J. (2024). Characterization of sexual maturity-associated N6-methyladenosine in boar testes. BMC Genom., 25.","DOI":"10.1186\/s12864-024-10343-w"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Lettieri, G., Notariale, R., Carusone, N., Giarra, A., Trifuoggi, M., Manna, C., and Piscopo, M. (2021). New Insights into Alterations in PL Proteins Affecting Their Binding to DNA after Exposure of Mytilus galloprovincialis to Mercury-A Possible Risk to Sperm Chromatin Structure?. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22115893"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Lettieri, G., Marinaro, C., Brogna, C., Montano, L., Lombardi, M., Trotta, A., Troisi, J., and Piscopo, M. (2023). A Metabolomic Analysis to Assess the Responses of the Male Gonads of Mytilus galloprovincialis after Heavy Metal Exposure. Metabolites, 13.","DOI":"10.3390\/metabo13121168"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Lettieri, G., Notariale, R., Ambrosino, A., Di Bonito, A., Giarra, A., Trifuoggi, M., Manna, C., and Piscopo, M. (2021). Spermatozoa Transcriptional Response and Alterations in PL Proteins Properties after Exposure of Mytilus galloprovincialis to Mercury. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22041618"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1016\/j.ecoenv.2018.11.069","article-title":"Alterations in the properties of sperm protamine-like II protein after exposure of Mytilus galloprovincialis (Lamarck 1819) to sub-toxic doses of cadmium","volume":"169","author":"Puoti","year":"2019","journal-title":"Ecotoxicol. Env. Saf."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2384564","DOI":"10.1080\/21505594.2024.2384564","article-title":"Porcine reproductive and respiratory syndrome virus infects the reproductive system of male piglets and impairs development of the blood-testis barrier","volume":"15","author":"Huang","year":"2024","journal-title":"Virulence"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"107606","DOI":"10.1016\/j.anireprosci.2024.107606","article-title":"Inhibition of testicular development by suppressing neonatal LH rise in male domestic pigs","volume":"270","author":"Park","year":"2024","journal-title":"Anim. Reprod. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"117246","DOI":"10.1016\/j.ecoenv.2024.117246","article-title":"Effect of iron-manganese oxide on the degradation of deoxynivalenol in feed and enhancement of growth performance and intestinal health in weaned piglets","volume":"286","author":"Wu","year":"2024","journal-title":"Ecotoxicol. Env. Saf."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1079\/PNS2004388","article-title":"Dietary antioxidants and environmental stress","volume":"63","author":"Kelly","year":"2004","journal-title":"Proc. Nutr. Soc."},{"key":"ref_17","first-page":"215","article-title":"Human Sperm Quality and Metal Toxicants: Protective Effects of some Flavonoids on Male Reproductive Function","volume":"10","author":"Jamalan","year":"2016","journal-title":"Int. J. Fertil. Steril."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"8946","DOI":"10.1007\/s11356-015-5263-3","article-title":"Detoxification effects of phytonutrients against environmental toxicants and sharing of clinical experience on practical applications","volume":"24","author":"Chung","year":"2017","journal-title":"Envorn. Sci. Pollut. Res. Int."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/j.foodchem.2014.05.132","article-title":"Quantitative metabolite profiling of edible onion species by NMR and HPLC-MS","volume":"165","author":"Soininen","year":"2014","journal-title":"Food Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/j.foodres.2017.08.034","article-title":"Allium tuberosum: Antidiabetic and hepatoprotective activities","volume":"102","author":"Tang","year":"2017","journal-title":"Food Res. Int."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Niu, K.-M., Kothari, D., Lee, W.-D., Cho, S., Wu, X., and Kim, S.-K. (2020). Optimization of Chinese Chive Juice as a Functional Feed Additive. Appl. Sci., 10.","DOI":"10.3390\/app10186194"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1007\/s13765-016-0166-7","article-title":"Characteristics of Chinese chives (Allium tuberosum) fermented by Leuconostoc mesenteroides","volume":"59","author":"Hong","year":"2016","journal-title":"Appl. Biol. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Kothari, D., Lee, W.-D., Niu, K.-M., and Kim, S.-K. (2019). The Genus Allium as Poultry Feed Additive: A Review. Animals, 9.","DOI":"10.3390\/ani9121032"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"113240","DOI":"10.1016\/j.foodres.2023.113240","article-title":"Transcriptomics and metabolomics reveal improved performance of Hu sheep on hybridization with Southdown sheep","volume":"173","author":"Kong","year":"2023","journal-title":"Food Res. Int."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Chu, T., Cui, J., Sun, L., Zhang, X., Sun, L., Tong, J., Li, L., Xiao, Y., Xu, L., and Zhang, L. (2024). The disordered extracellular matrix landscape induced endometrial fibrosis of sheep: A multi-omics integrative analysis. Int. J. Biol. Macromol., 265.","DOI":"10.1016\/j.ijbiomac.2024.130845"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1146\/annurev-genet-080320-040045","article-title":"Decoding the Spermatogenesis Program: New Insights from Transcriptomic Analyses","volume":"56","author":"Rabbani","year":"2022","journal-title":"Annu. Rev. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Fu, X., Yang, Y., Yan, Z., Liu, M., and Wang, X. (2022). Transcriptomic Study of Spermatogenesis in the Testis of Hu Sheep and Tibetan Sheep. Genes, 13.","DOI":"10.3390\/genes13122212"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"110581","DOI":"10.1016\/j.ygeno.2023.110581","article-title":"Metabolomic and transcriptomic profiles after immune stimulation in the zebrafish testes","volume":"115","author":"Ladisa","year":"2023","journal-title":"Genomics"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1002\/med.20067","article-title":"Combining docking and molecular dynamic simulations in drug design","volume":"26","author":"Alonso","year":"2006","journal-title":"Med. Res. Rev."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Xing, K., Zhu, F., Zhai, L., Liu, H., Wang, Z., Hou, Z., and Wang, C. (2014). The liver transcriptome of two full-sibling Songliao black pigs with extreme differences in backfat thickness. J. Anim. Sci. Biotechnol., 5.","DOI":"10.1186\/2049-1891-5-32"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/s12522-011-0118-1","article-title":"Testicular volume discrepancy is associated with decreased semen quality in infertile Japanese males with varicoceles","volume":"11","author":"Komiya","year":"2012","journal-title":"Reprod. Med. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Yang, Z., Guo, Q., Kong, X., Li, Y., and Li, F. (2024). Effects of Flavonoids in Fructus Aurantii Immaturus on Carcass Traits, Meat Quality and Antioxidant Capacity in Finishing Pigs. Antioxidants, 13.","DOI":"10.3390\/antiox13111385"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"i884","DOI":"10.1093\/bioinformatics\/bty560","article-title":"fastp: An ultra-fast all-in-one FASTQ preprocessor","volume":"34","author":"Chen","year":"2018","journal-title":"Bioinformatics"},{"key":"ref_34","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_35","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1093\/bioinformatics\/btu638","article-title":"HTSeq--a Python framework to work with high-throughput sequencing data","volume":"31","author":"Anders","year":"2015","journal-title":"Bioinformatics"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Love, M.I., Huber, W., and Anders, S. (2014). Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol., 15.","DOI":"10.1186\/s13059-014-0550-8"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Smedley, D., Haider, S., Ballester, B., Holland, R., London, D., Thorisson, G., and Kasprzyk, A. (2009). BioMart\u2014Biological queries made easy. BMC Genom., 10.","DOI":"10.1186\/1471-2164-10-22"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"The Gene Ontology Consortium (2019). The Gene Ontology Resource: 20 years and still GOing strong. Nucleic Acids Res., 47, D330\u2013D338.","DOI":"10.1093\/nar\/gky1055"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"D480","DOI":"10.1093\/nar\/gkm882","article-title":"KEGG for linking genomes to life and the environment","volume":"36","author":"Kanehisa","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1089\/omi.2011.0118","article-title":"clusterProfiler: An R package for comparing biological themes among gene clusters","volume":"16","author":"Yu","year":"2012","journal-title":"Omics"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"D607","DOI":"10.1093\/nar\/gky1131","article-title":"STRING v11: Protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets","volume":"47","author":"Szklarczyk","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: A software environment for integrated models of biomolecular interaction networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1021\/ac051437y","article-title":"XCMS: Processing mass spectrometry data for metabolite profiling using nonlinear peak alignment, matching, and identification","volume":"78","author":"Smith","year":"2006","journal-title":"Anal. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1007\/s11306-012-0434-4","article-title":"Mass appeal: Metabolite identification in mass spectrometry-focused untargeted metabolomics","volume":"9","author":"Dunn","year":"2013","journal-title":"Metabolomics"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"D587","DOI":"10.1093\/nar\/gkac963","article-title":"KEGG for taxonomy-based analysis of pathways and genomes","volume":"51","author":"Kanehisa","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1038\/ng1180","article-title":"PGC-1\u03b1-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes","volume":"34","author":"Mootha","year":"2003","journal-title":"Nat. Genet."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Yang, L., Lai, X., Lin, F., Shi, N., Xu, X., Wang, H., Li, X., Shen, D., Qian, H., and Jin, X. (2025). Revitalising Aging Oocytes: Echinacoside Restores Mitochondrial Function and Cellular Homeostasis Through Targeting GJA1\/SIRT1 Pathway. Cell Prolif., e70044.","DOI":"10.1111\/cpr.70044"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1859","DOI":"10.1002\/jcc.20945","article-title":"CHARMM-GUI: A web-based graphical user interface for CHARMM","volume":"29","author":"Jo","year":"2008","journal-title":"J. Comput. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"9954","DOI":"10.1021\/jp003020w","article-title":"Structure and Dynamics of the TIP3P, SPC, and SPC\/E Water Models at 298 K","volume":"105","author":"Mark","year":"2001","journal-title":"J. Phys. Chem. A"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"118644","DOI":"10.1016\/j.carbpol.2021.118644","article-title":"Application of molecular docking in elaborating molecular mechanisms and interactions of supramolecular cyclodextrin","volume":"276","author":"Li","year":"2022","journal-title":"Carbohydr. Polym."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2209","DOI":"10.21037\/tau-24-274","article-title":"Comparison of different processed products of Allium tuberosum Rottler for the treatment of mice asthenozoospermia","volume":"13","author":"Wu","year":"2024","journal-title":"Transl. Androl. Urol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1002\/j.1939-4640.1997.tb02440.x","article-title":"Haptoglobin is a Sertoli cell product in the rat seminiferous epithelium: Its purification and regulation","volume":"18","author":"Grima","year":"1997","journal-title":"J. Androl."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Li, Z., Zhao, Y., Zong, Q., Hu, P., Bao, W., Liu, H.-Y., and Cai, D. (2023). Lactoferrin Restores the Deoxynivalenol-Impaired Spermatogenesis and Blood\u2013Testis Barrier Integrity via Improving the Antioxidant Capacity and Modifying the Cell Adhesion and Inflammatory Response. Antioxidants, 12.","DOI":"10.3390\/antiox12010152"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Dai, P., Zou, M., Cai, Z., Zeng, X., Zhang, X., and Liang, M. (2024). pH homeodynamics and male fertility: A coordinated regulation of acid-based balance during sperm journey to fertilization. Biomolecules, 14.","DOI":"10.3390\/biom14060685"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1093\/biolre\/ioac039","article-title":"Calcium-binding proteins S100A8, S100A9, and S100A12: Expression and regulation at the maternal-conceptus interface in pigs","volume":"106","author":"Jang","year":"2022","journal-title":"Biol. Reprod."},{"key":"ref_57","first-page":"1","article-title":"Short Communication: Molecular cloning and expression pattern of the porcine 5-aminolevulinate synthase 1 (ALAS1) gene and its association with reproductive traits","volume":"15","author":"Liu","year":"2016","journal-title":"Genet. Mol. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1111\/j.1365-2605.2006.00740.x","article-title":"Comprehensive analysis of gene expression in testes producing haploid germ cells using DNA microarray analysis","volume":"30","author":"Ike","year":"2007","journal-title":"Int. J. Androl."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Ling, X., Wang, Q., Zhang, J., and Zhang, G. (2023). Genome-wide analysis of the KLF gene family in chicken: Characterization and expression profile. Animals, 13.","DOI":"10.3390\/ani13091429"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.theriogenology.2023.02.013","article-title":"MMPs, ADAMs and ADAMTSs are associated with mammalian sperm fate","volume":"200","author":"Li","year":"2023","journal-title":"Theriogenology"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"866","DOI":"10.21037\/atm-20-654","article-title":"Immune-related genes play an important role in the prognosis of patients with testicular germ cell tumor","volume":"8","author":"Ji","year":"2020","journal-title":"Ann. Transl. Med."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Luo, Z., Zhu, J., Fang, Z., Xu, R., Wan, R., He, Y., Chen, Y., Chen, S., Wang, Q., and Liu, Q. (2024). Exercise-augmented THSD7B exhibited a positive prognostic implication and tumor-suppressed functionality in pan-cancer. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1440226"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1016\/j.bbagrm.2016.04.005","article-title":"TOX3 regulates neural progenitor identity","volume":"1859","author":"Sahu","year":"2016","journal-title":"Biochim. Biophys. Acta-Gene Regul. Mech."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1242\/jcs.068759","article-title":"TOX3 is a neuronal survival factor that induces transcription depending on the presence of CITED1 or phosphorylated CREB in the transcriptionally active complex","volume":"124","author":"Dittmer","year":"2011","journal-title":"J. Cell Sci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"4626","DOI":"10.1038\/s41467-019-12522-w","article-title":"Rare mutations in the complement regulatory gene CSMD1 are associated with male and female infertility","volume":"10","author":"Lee","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1832","DOI":"10.1017\/S1751731115000907","article-title":"Gene expression during testis development in Duroc boars","volume":"9","author":"Lervik","year":"2015","journal-title":"Animal"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.metabol.2019.06.002","article-title":"PPP1R3C mediates metformin-inhibited hepatic gluconeogenesis","volume":"98","author":"Ji","year":"2019","journal-title":"Metabolism"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1089\/dna.2013.2084","article-title":"Overexpression of TDRP1 gene in swine testis cell and its global transcriptome analysis","volume":"32","author":"Liu","year":"2013","journal-title":"DNA Cell Biol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"198","DOI":"10.3390\/biochem2030014","article-title":"Testicular glycogen metabolism: An overlooked source of energy for spermatogenesis?","volume":"2","author":"Silva","year":"2022","journal-title":"BioChem"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.theriogenology.2020.05.027","article-title":"Proteomic analysis reveals key proteins involved in arginine promotion of testicular development in boars","volume":"154","author":"Lin","year":"2020","journal-title":"Theriogenology"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.5713\/ab.23.0057","article-title":"Phylogenetic and expression analysis of the angiopoietin-like gene family and their role in lipid metabolism in pigs","volume":"36","author":"Zheng","year":"2023","journal-title":"Anim. Biosci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.1016\/j.bbrc.2006.05.042","article-title":"Regulation of intracellular levels of NAD: A novel role for CD38","volume":"345","author":"Aksoy","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"103515","DOI":"10.1016\/j.dci.2019.103515","article-title":"CD38 play roles in T cell-dependent response and B cell differentiation in nile tilapia (Oreochromis niloticus)","volume":"103","author":"Li","year":"2020","journal-title":"Dev. Comp. Immunol."},{"key":"ref_74","first-page":"4930","article-title":"Mast cell and macrophage chemokines CXCL1\/CXCL2 control the early stage of neutrophil recruitment during tissue inflammation","volume":"121","author":"Dudeck","year":"2013","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1007\/s00404-013-2801-4","article-title":"Influence of reactive oxygen species on human sperm functions and fertilizing capacity including therapeutical approaches","volume":"288","author":"Chen","year":"2013","journal-title":"Arch. Gynecol. Obs."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2103","DOI":"10.7150\/jca.104376","article-title":"Identification and Characterization of Oxidative Stress and Endoplasmic Reticulum Stress-Related Genes in Esophageal Cancer","volume":"16","author":"Li","year":"2025","journal-title":"J. Cancer"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"8810785","DOI":"10.1155\/2020\/8810785","article-title":"The molecular mechanisms of regulating oxidative stress-induced Ferroptosis and therapeutic strategy in tumors","volume":"2020","author":"Zhu","year":"2020","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Marini, H.R., Micali, A., Squadrito, G., Puzzolo, D., Freni, J., Antonuccio, P., and Minutoli, L. (2022). Nutraceuticals: A New Challenge against Cadmium-Induced Testicular Injury. Nutrients, 14.","DOI":"10.3390\/nu14030663"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"109398","DOI":"10.1016\/j.ecoenv.2019.109398","article-title":"Infliximab abrogates cadmium-induced testicular damage and spermiotoxicity via enhancement of steroidogenesis and suppression of inflammation and apoptosis mediators","volume":"182","author":"Habib","year":"2019","journal-title":"Ecotoxicol. Env. Saf."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"100454","DOI":"10.1016\/j.advnut.2025.100454","article-title":"Mediterranean Diet, Semen Quality, and Medically Assisted Reproductive Outcomes in the Male Population: A Systematic Review and Meta-Analysis","volume":"16","author":"Agarwal","year":"2025","journal-title":"Adv. Nutr."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.euf.2021.01.017","article-title":"Effects of a Lifestyle Change Intervention on Semen Quality in Healthy Young Men Living in Highly Polluted Areas in Italy: The FASt Randomized Controlled Trial","volume":"8","author":"Montano","year":"2022","journal-title":"Eur. Urol. Focus."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1093\/humupd\/dmx006","article-title":"Dietary patterns, foods and nutrients in male fertility parameters and fecundability: A systematic review of observational studies","volume":"23","year":"2017","journal-title":"Hum. Reprod. Update"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.reprotox.2017.06.170","article-title":"The role of the Mediterranean diet on sperm morphology in healthy men living in polluted area (EcoFoodFertility project)","volume":"72","author":"Montano","year":"2017","journal-title":"Reprod. Toxicol."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Piera-Jordan, C., Prieto Huecas, L., Serrano De La Cruz Delgado, V., Zaragoza Mart\u00ed, A., Garc\u00eda Velert, M.B., Tordera Terrades, C., S\u00e1nchez-SanSegundo, M., Hurtado-S\u00e1nchez, J.A., Tuells, J., and Mart\u00edn Manchado, L. (2024). Influence of the Mediterranean diet on seminal quality-a systematic review. Front. Nutr., 11.","DOI":"10.3389\/fnut.2024.1287864"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1007\/s00394-021-02761-3","article-title":"Mediterranean dietary pattern and the risk of type 2 diabetes: A systematic review and dose-response meta-analysis of prospective cohort studies","volume":"61","author":"Jayedi","year":"2022","journal-title":"Eur. J. Nutr."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1007\/s00394-020-02346-6","article-title":"An updated systematic review and meta-analysis on adherence to mediterranean diet and risk of cancer","volume":"60","author":"Morze","year":"2021","journal-title":"Eur. J. Nutr."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Saetan, U., and Chotigeat, W. (2023). Differentially expressed genes in the testes from early to mature development of banana shrimp (Fenneropenaeus merguiensis). PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0292127"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Liu, P., Li, Z., Zhang, Q., Qiao, J., Zheng, C., Zheng, W., and Zhang, H. (2024). Identification of testis development-related genes by combining Iso-Seq and RNA-Seq in Zeugodacus tau. Front. Cell Dev. Biol., 12.","DOI":"10.3389\/fcell.2024.1356151"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1016\/j.ajhg.2022.05.009","article-title":"Identification and functional evaluation of GRIA1 missense and truncation variants in individuals with ID: An emerging neurodevelopmental syndrome","volume":"109","author":"Ismail","year":"2022","journal-title":"Am. J. Hum. Genet."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Biondi, B., De Pascale, L., Mardirossian, M., Di Stasi, A., Favaro, M., Scocchi, M., and Peggion, C. (2023). Structural and biological characterization of shortened derivatives of the cathelicidin PMAP-36. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-41945-1"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Scheenstra, M.R., van den Belt, M., Tjeerdsma-van Bokhoven, J.L., Schneider, V.A., Ordonez, S.R., van Dijk, A., Veldhuizen, E.J., and Haagsman, H.P. (2019). Cathelicidins PMAP-36, LL-37 and CATH-2 are similar peptides with different modes of action. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-41246-6"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jsbmb.2015.02.014","article-title":"2\u03b2- and 16\u03b2-hydroxylase activity of CYP11A1 and direct stimulatory effect of estrogens on pregnenolone formation","volume":"150","author":"Mosa","year":"2015","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.str.2022.11.010","article-title":"Structural basis for Y2 receptor-mediated neuropeptide Y and peptide YY signaling","volume":"31","author":"Kang","year":"2023","journal-title":"Structure"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1097\/WNR.0000000000001324","article-title":"Gastrin-releasing peptide inhibits CA1 neurons via increasing inhibitory synaptic transmissions in hippocampal slices of rats","volume":"30","author":"Yao","year":"2019","journal-title":"NeuroReport"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1007\/s11060-023-04548-4","article-title":"CPLX2 is a novel tumor suppressor and improves the prognosis in glioma","volume":"167","author":"Chen","year":"2024","journal-title":"J. Neuro-Oncol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1093\/advances\/nmaa181","article-title":"Diet and the microbiota\u2013gut\u2013brain axis: Sowing the seeds of good mental health","volume":"12","author":"Berding","year":"2021","journal-title":"Adv. Nutr."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s40035-025-00476-7","article-title":"Nootropic foods in neurodegenerative diseases: Mechanisms, challenges, and future","volume":"14","author":"Nguyen","year":"2025","journal-title":"Transl. Neurodegener."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1111\/all.15541","article-title":"Metabolic regulation by prostaglandin E2 impairs lung group 2 innate lymphoid cell responses","volume":"78","author":"Robb","year":"2023","journal-title":"Allergy"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"110781","DOI":"10.1016\/j.exger.2019.110781","article-title":"Collagens and elastin genetic variations and their potential role in aging-related diseases and longevity in humans","volume":"129","author":"Kenny","year":"2020","journal-title":"Exp. Gerontol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"223","DOI":"10.3892\/ol.2021.12484","article-title":"Differential expression of COL4A3 and collagen in upward and downward progressing types of nasopharyngeal carcinoma","volume":"21","author":"Yang","year":"2021","journal-title":"Oncol. Lett."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Ipsa, E., Cruzat, V.F., Kagize, J.N., Yovich, J.L., and Keane, K.N. (2019). Growth hormone and insulin-like growth factor action in reproductive tissues. Front. Endocrinol., 10.","DOI":"10.3389\/fendo.2019.00777"}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/14\/9\/1056\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:34:43Z","timestamp":1760034883000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/14\/9\/1056"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,28]]},"references-count":101,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["antiox14091056"],"URL":"https:\/\/doi.org\/10.3390\/antiox14091056","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,28]]}}}