Identification of Key Genes and Pathway Associated with Subfertility in Bos Taurus: a Bioinformatics Study

Document Type : Full Research Paper

Authors

1 Department of Animal Science, Faculty of Agriculture, Lorestan University, Khorramabad, Iran.

2 2- Department of Animal Science, Faculty of Agriculture, Lorestan University, Khorramabad, Iran. Email address

Abstract

Subfertility is an important issue in dairy cow industry which can negatively eclipse economics of a farm. Thereby, investigation of the biological phenomena which can lead to subfertility is crucial. The current study was designed to identify hub genes and biological pathways related to subfertility. In this case, an endometrial gene expression profile including 6 fertile and 5 subfertile samples of Bos taurus was collected from database. First, up-regulated and down-regulated differentially expressed genes of the samples were screened by Geo2R server. Then, protein-protein interaction network analysis, module analysis, gene ontology enrichment analysis, pathway analysis and hub gene identification of differentially expressed genes were conducted using reliable tools and software. Based on the results of comparison between fertile and subfertile samples, 169 genes were identified as differentially expressed genes which contained 53 and 116 up-regulated and down-regulated genes, respectively. Moreover, the results of module analysis confirmed existence of four clusters which their scores were between 2.8 and 3. The results of gene ontology enrichment analysis revealed that neurotransmitter secretion, extracellular space, steroid dehydrogenase activity, synaptic vesicle cycle were the most significant terms of biological process, cellular compartment, molecular function and KEGG pathway, respectively. Finally, the results revealed that 5 genes including SYT1, ITGAM, HABP2, CHGA and TAT were hub genes which can be introduced as a proper molecular marker for breeding and management of cattle reproduction programs.

Keywords

Main Subjects


1- Alhajeri, M. M., R. R. Alkhanjari, R. Hodeify, A. Khraibi and H. Hamdan. 2022. Neurotransmitters, neuropeptides and calcium in oocyte maturation and early development. Frontiers in Cell and Developmental Biology 10.
2- Altmäe, S., M. Koel, U. Võsa, P. Adler, M. Suhorutšenko, T. Laisk-Podar, V. Kukushkina, M. Saare, A. Velthut-Meikas and K. Krjutškov. 2017. Meta-signature of human endometrial receptivity: a meta-analysis and validation study of transcriptomic biomarkers. Scientific reports 7: 10077.
3- Arechiga-Flores, C. F., Z. Cortés-Vidauri, P. Hernández-Briano, R. R. Lozano-Domínguez, M. A. López-Carlos, U. Macías-Cruz and L. Avendaño-Reyes. 2022. Hypocalcemia in the dairy cow. Review. Revista mexicana de ciencias pecuarias 13: 1025-1054.
4- Beerda, B., J. Wyszynska-Koko, M. Te Pas, A. De Wit and R. Veerkamp. 2008. Expression profiles of genes regulating dairy cow fertility: recent findings, ongoing activities and future possibilities. Animal 2: 1158-1167.
5- Bersinger, N. A., D. M. Wunder, M. H. Birkhäuser and M. D. Mueller. 2008. Gene expression in cultured endometrium from women with different outcomes following IVF. MHR: Basic science of reproductive medicine 14: 475-484.
6- Chapman, E. R. 2008. How does synaptotagmin trigger neurotransmitter release? Annu Rev Biochem 77: 615-641.
7- Chin, C.-H., S.-H. Chen, H.-H. Wu, C.-W. Ho, M.-T. Ko and C.-Y. Lin. 2014. cytoHubba: identifying hub objects and sub-networks from complex interactome. BMC systems biology 8: 1-7.
8- Craxton, M. 2004. Synaptotagmin gene content of the sequenced genomes. BMC genomics 5: 1-14.
9- Darang, E., Z. Pezeshkian, S. Z. Mirhoseini and S. Ghovvati. 2022. Identification of Key Genes and Potential Pathways Associated with Mastitis Induced by E. coli. Biochemical Genetics: 1-19.
10- Davis, S. and P. S. Meltzer. 2007. GEOquery: a bridge between the Gene Expression Omnibus (GEO) and BioConductor. Bioinformatics 23: 1846-1847.
11- Fonseca, L. F. S., D. B. dos Santos Silva, D. F. J. Gimenez, F. Baldi, J. A. Ferro, L. A. L. Chardulo and L. G. de Albuquerque. 2020. Gene expression profiling and identification of hub genes in Nellore cattle with different marbling score levels. Genomics 112: 873-879.
12- Ju, X., Z. Wang, D. Cai, H. Xu, S. F. Bello, S. Zhang, W. Zhu, C. Ji and Q. Nie. 2023. TAT gene polymorphism and its relationship with production traits in Muscovy ducks (Cairina Moschata). Poultry Science 102: 102551.
13- Liu, G., M. Zeng, X. Li, Y. Rong, Z. Hu, H. Zhang and X. Liu. 2021. Expression and analysis of ESR1, IGF-1, FSH, VLDLR, LRP, LH, PRLR genes in Pekin duck and Black Muscovy duck. Gene 769: 145183.
14- Mahen, P. J., H. J. Williams, R. F. Smith and D. Grove‐White. 2018. Effect of blood ionised calcium concentration at calving on fertility outcomes in dairy cattle. Veterinary Record 183: 263-263.
15- Matsuyama, S., T. Kojima, S. Kato and K. Kimura. 2012. Relationship between quantity of IFNT estimated by IFN-stimulated gene expression in peripheral blood mononuclear cells and bovine embryonic mortality after AI or ET. Reproductive Biology and Endocrinology 10: 1-10.
16- Mullen, M. P., G. Elia, M. Hilliard, M. H. Parr, M. G. Diskin, A. C. Evans and M. A. Crowe. 2012. Proteomic characterization of histotroph during the preimplantation phase of the estrous cycle in cattle. Journal of proteome research 11: 3004-3018.
17- Norman, H., L. Walton and J. Dürr. 2017. Reproductive status of cows in Dairy Herd Improvement programs and bred using artificial insemination. Council on dairy cattle breeding (CDCB) website[Accessed on 2020 Apr 20] https://queries uscdcb com/publish/dhi/current/reproall html.
18- Perez-Marin, C. C., L. Molina Moreno and C. Vizuete. 2012. Clinical approach to the repeat breeder cow syndrome. A Bird's-Eye View of Veterinary Medicine: 337-362.
19- Perin, M. S., V. A. Fried, G. A. Mignery, R. Jahn and T. C. Südhof. 1990. Phospholipid binding by a synaptic vesicle protein homologous to the regulatory region of protein kinase C. Nature 345: 260-263.
20- Pezeshkian, Z., S. Z. Mirhoseini and S. Ghovvati. 2022. Identification of hub genes involved in apparent metabolizable energy of chickens. Animal Biotechnology 33: 242-249.
21- Rosetti, F., A. de la Cruz and J. C. Crispín. 2019. Gene-function studies in systemic lupus erythematosus. Current Opinion in Rheumatology 31: 185-192.
22- Saheki, Y. and P. De Camilli. 2017. The extended-synaptotagmins. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research 1864: 1490-1493.
23- Szklarczyk, D., A. L. Gable, D. Lyon, A. Junge, S. Wyder, J. Huerta-Cepas, M. Simonovic, N. T. Doncheva, J. H. Morris and P. Bork. 2019. STRING v11: protein–protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic acids research 47: D607-D613.
24- Wolf, E., S. Hiendleder, S. Bauersachs, T. Fröhlich, F. Sinowatz, H. Blum and G. J. Arnold. 2006. Methods for transcriptome and proteome research: applications for studying the biology of reproduction in cattle. Berliner und Munchener tierarztliche Wochenschrift 119: 7-16.
25- Xiu-Lan, Z., L. Shi-Fen, Z. Xi-Qian, X. Hong, L. Yan-Qun, Y. Yan-Hong, L. Li-Juan, Z. Chun-Hui, S. Heide and L. Feng-Hua. 2020. Synaptotagmin 1 regulates cortical granule exocytosis during mouse oocyte activation.
26- Yang, W., J. Ma, W. Zhou, Z. Li, X. Zhou, B. Cao, Y. Zhang, J. Liu, Z. Yang and H. Zhang. 2019. Identification of hub genes and outcome in colon cancer based on bioinformatics analysis. Cancer Management and Research 11: 323.
27- Zekarias, T., E. Demissie, W. Ahmed, T. Dema and A. Amsalu. 2019. Non-Infectious Causes of Infertility in Dairy. Cows: A Review Journal of Reproduction and Infertility 10: 51-57.