Journal Article

Identification of key genes related to unilateral cryptorchidism in sheep by comprehensive transcriptomics and proteomics analyses

Yuan, Ze-Hu, Wang, Zhong-Yu, Liu, Yang-Kai, Li, Wan-Hong, Li, Fa-Di, Yue, Xiang-Peng, Pei, Sheng-Wei

2025

Overview

Background Cryptorchidism is one of the most common reproductive abnormalities in rams, which seriously harms the reproductive capacity of rams and causes significant economic losses to the sheep industry. However, there are few studies elucidating its hereditary predisposition in sheep. Results In the present study, the transcriptome and proteome of the cryptic (CT) and contralateral (CLT) testis from four unilaterally cryptorchid rams, and the normal testis (NT) from four healthy rams were analyzed using RNA-seq and TMT-based proteomics, respectively. A total of 10,357, 10,175, and 132 differentially expressed genes (DEGs) were identified between CT vs. CLT, CT vs. NT, and CLT vs. NT. Venn diagram showed that 9744 DEGs (5499 up-regulated and 4245 down-regulated) shared in CT vs. CLT and CT vs. NT. Functional enrichment analysis revealed that 5499 up-regulated DEGs were mainly involved in regulation of programmed cell death and metabolic process, while 4245 down-regulated DEGs were closely related to reproductive process, such as spermatogenesis, sexual reproduction, reproduction and male gamete generation. Furthermore, 325 overlapped genes (114 up-regulated and 211 down-regulated) between DEGs and DAPs that shared the same regulatory status were identified by combining transcriptomics and proteomics. Ten genes, including AKAP4 , AKAP3 , FSIP2 , HSPA1L , HSPA4L , TUBB , TXNRD2 , CDC42 , PGK1 and HSPA1A , were identified as candidate key genes related to unilateral cryptorchidism. Conclusion Our results revealed that both gene and protein expression in the cryptic testis of unilateral cryptorchid rams is massively altered. Bioinformatics analysis unveiled several candidate genes and signaling pathways potentially involved in unilateral cryptorchidism. These findings provide new insights into the molecular mechanism underlying spermatogenesis failure caused by cryptorchidism.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Abnormalities / Animal Genetics and Genomics / Animals / Apoptosis / Bioinformatics / Biomedical and Life Sciences / Cdc42 protein / Cell death / Congenital diseases / Cryptorchidism / Cryptorchidism - genetics / Cryptorchidism - metabolism / Cryptorchidism - veterinary / Cryptorchism / Economic impact / Fertility / Gene expression / Gene Expression Profiling / Gene set enrichment analysis / Genes / Genetic aspects / Genomes / Health aspects / Health risk assessment / Infertility / Life Sciences / Male / Methods / Microarrays / Microbial Genetics and Genomics / Molecular modelling / Pathogenesis / Plant Genetics and Genomics / Proteome / Proteomes / Proteomics / Proteomics - methods / Rams / Risk factors / RNA sequencing / Sexual reproduction / Sheep / Sheep - genetics / Sheep Diseases - genetics / Sheep Diseases - metabolism / Software / Spermatogenesis / Testes / Testis / Testis - metabolism / Transcriptome / Transcriptomes / Transcriptomics / Venn diagrams