Frontiers in Medical Science Research, 2023, 5(12); doi: 10.25236/FMSR.2023.051202.
Xiaodong Zhao1, Meng Zhao2, Peng Luo1, Zhenyu Wang1, Huifang Liao3, Jinchan Zhang3, Xianliang Zeng1
1Pediatric Surgery, Heyuan Maternal and Child Health Hospital, Heyuan, China
2Country Obstetrics and Gynecology, Heyuan Maternal and Child Health Hospital, Heyuan, China
3Medical Department, Heyuan Maternal and Child Health Hospital, Heyuan, China
Despite the growing evidence that the presence of cryptorchidism increases the risk of azoospermia, the common mechanisms via which it occurs remain incompletely elucidated. This research was conducted to gain a deeper understanding of the molecular mechanisms that contribute to the onset and progression of this complication. In total, 197 common DEGs (182 down-regulated and 15 up-regulated genes) were chosen for further investigation. The significance of cell cycle and metabolic regulation in the onset and progression of both diseases was highlighted by functional analysis. Eventually, nine important hub genes were identified using cystoHubba, including CCNB1, PCNA, AURKA, CCT5, CCT2, STIP1, UBE2N, RUVBL1, and HSF1. Our research elucidates a common pathogenesis between cryptorchidism and azoospermia. These common pathways and hub genes might inspire new avenues of investigation into underlying mechanisms.
cryptorchidism; azoospermia; bioinformatics; differentially expressed genes; hub genes
Xiaodong Zhao, Meng Zhao, Peng Luo, Zhenyu Wang, Huifang Liao, Jinchan Zhang, Xianliang Zeng. Exploring the Pathogenesis of Cryptorchidism Complicated with Azoospermia via Microarray Data Analysis. Frontiers in Medical Science Research (2023) Vol. 5, Issue 12: 12-25. https://doi.org/10.25236/FMSR.2023.051202.
[1] Urry, R L et al. “The incidence of antisperm antibodies in infertility patients with a history of cryptorchidism.” The Journal of urology vol. 151, 2 (1994): 381-3. doi:10.1016/s0022-5347(17)34954-6
[2] Rodprasert, Wiwat et al. “Hypogonadism and Cryptorchidism.” Frontiers in endocrinology vol. 10 906. 15 Jan. 2020, doi:10.3389/fendo.2019.00906
[3] Sinisi A A, Pasquali D, Papparella A, et al. Antisperm antibodies in cryptorchidism before and after surgery[J]. The Journal of urology, 1998, 160(5): 1834-1837.
[4] Hadziselimovic, Faruk et al. “Gene Expression Changes Underlying Idiopathic Central Hypogonadism in Cryptorchidism with Defective Mini-Puberty.” Sexual development: genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation vol. 10,3 (2016): 136–146. doi:10.1159/000447762
[5] Hadziselimovic, F, and B Herzog. “The importance of both an early orchidopexy and germ cell maturation for fertility.” Lancet (London, England) vol. 358, 9288 (2001): 1156-1157. doi:10.1016/S0140-6736(01)06274-2
[6] Schoenwolf GC, Bleyl SB, Brauer PR, Francis‐West PH.Larsen's Human Embryology. Philadelphia, PA: Elsevier; 2021.
[7] Gegenschatz-Schmid, Katharina et al. “DMRTC2, PAX7, BRACHYURY/T and TERT Are Implicated in Male Germ Cell Development Following Curative Hormone Treatment for Cryptorchidism-Induced Infertility.” Genes vol. 8,10 267. 11 Oct. 2017, doi:10.3390/genes8100267
[8] Edgar R, Domrachev M, Lash AE.Gene Expression Omnibus: NCBI gene expression and hybridization array data repository Nucleic Acids Res. 2002 Jan 1; 30(1):207-210.
[9] The Gene Ontology resource: enriching a GOld mine. Nucleic Acids Res. Jan 2021;49(D1):D325-D334.
[10] Dechao Bu, Haitao Luo, et al., KOBAS-i: intelligent prioritization and exploratory visualization of biological functions for gene enrichment analysis, Nucleic Acids Research, Volume 49, Issue W1, 2 July 2021, Pages W317–W325.
[11] Franceschini, Andrea et al. “STRING v9.1: protein-protein interaction networks, with increased coverage and integration.” Nucleic acids research vol. 41,Database issue (2013): D808-D815. doi:10.1093/nar/gks1094
[12] Smoot, Michael E et al. “Cytoscape 2.8: new features for data integration and network visualization.” Bioinformatics (Oxford, England) vol. 27,3 (2011): 431-432. doi:10.1093/bioinformatics/btq675
[13] Warde-Farley, David et al. “The GeneMANIA prediction server: biological network integration for gene prioritization and predicting gene function.” Nucleic acids research vol. 38,Web Server issue (2010): W214-W220. doi:10.1093/nar/gkq537
[14] Han, Heonjong et al. “TRRUST v2: an expanded reference database of human and mouse transcriptional regulatory interactions.” Nucleic acids research vol. 46,D1 (2018): D380-D386. doi:10.1093/nar/gkx1013
[15] Nassau, Daniel E et al. “The pediatric patient and future fertility: optimizing long-term male reproductive health outcomes.” Fertility and sterility vol. 113,3 (2020): 489-499. doi:10.1016/j.fertnstert.2020.01.003
[16] Barthold, Julia Spencer et al. “Genetic, Maternal, and Environmental Risk Factors for Cryptorchidism: An Update.” European journal of pediatric surgery : official journal of Austrian Association of Pediatric Surgery ... [et al] = Zeitschrift fur Kinderchirurgie vol. 26,5 (2016): 399-408. doi:10.1055/s-0036-1592416
[17] de Rooij, D G, and J A Grootegoed. “Spermatogonial stem cells.” Current opinion in cell biology vol. 10,6 (1998): 694-701. doi:10.1016/s0955-0674(98)80109-9
[18] Papaioannou, Marilena D, and Serge Nef. “microRNAs in the testis: building up male fertility.” Journal of andrology vol. 31,1 (2010): 26-33. doi:10.2164/jandrol.109.008128
[19] Hadziselimovic, Faruk. “On the descent of the epididymo-testicular unit, cryptorchidism, and prevention of infertility.” Basic and clinical andrology vol. 27 21. 14 Nov. 2017, doi:10.1186/s12610-017-0065-8
[20] Jia, Hongshuai et al. “AKT3 and related molecules as potential biomarkers responsible for cryptorchidism and cryptorchidism-induced azoospermia.” Translational pediatrics vol. 10,7 (2021): 1805-1817. doi:10.21037/tp-21-31
[21] Tang, Ji-Xin et al. “Requirement for CCNB1 in mouse spermatogenesis.” Cell death & disease vol. 8,10 e3142. 26 Oct. 2017, doi:10.1038/cddis.2017.555
[22] Chen, Li et al. “Septin 4 controls CCNB1 stabilization via APC/CCDC20 during meiotic G2/M transition in mouse oocytes.” Journal of cellular physiology vol. 237,1 (2022): 730-742. doi:10.1002/jcp.30498
[23] Ibis, Muhammed Arif et al. “Can PCNA and LIM15 gene expression levels predict sperm retrieval success in men with non-obstructive azoospermia?.” Revista internacional de andrologia vol. 20 Suppl 1 (2022): S31-S38. doi:10.1016/j.androl.2021.04.002
[24] Nikonova, Anna S et al. “Aurora A kinase (AURKA) in normal and pathological cell division.” Cellular and molecular life sciences : CMLS vol. 70,4 (2013): 661-687. doi:10.1007/s00018-012-1073-7
[25] Lester, William C et al. “Aurora A Kinase (AURKA) is required for male germline maintenance and regulates sperm motility in the mouse.” Biology of reproduction vol. 105,6 (2021): 1603-1616. doi:10.1093/biolre/ioab168
[26] Odunuga, O O et al. “Hop: more than an Hsp70/Hsp90 adaptor protein.” BioEssays : news and reviews in molecular, cellular and developmental biology vol. 26,10 (2004): 1058-1068.doi:10.1002/bies.20107
[27] Wang, Yanwei et al. “Systematic study of stress-inducible protein 1 (Stip1) in male reproductive system and its expression during stress response.” Gene vol. 554,1 (2015): 58-63. doi:10.1016/j.gene.2014.10.023