Transcriptome profiling of mice testes following low dose irradiation

Abstract

BackgroundRadiotherapy is used routinely to treat testicular cancer. Testicular cells vary in radio-sensitivity and the aim of this study was to investigate cellular and molecular changes caused by low dose irradiation of mice testis and to identify transcripts from different cell types in the adult testis.MethodsTranscriptome profiling was performed on total RNA from testes sampled at various time points (n = 17) after 1 Gy of irradiation. Transcripts displaying large overall expression changes during the time series, but small expression changes between neighbouring time points were selected for further analysis. These transcripts were separated into clusters and their cellular origin was determined. Immunohistochemistry and in silico quantification was further used to study cellular changes post-irradiation (pi).ResultsWe identified a subset of transcripts (n = 988) where changes in expression pi can be explained by changes in cellularity. We separated the transcripts into five unique clusters that we associated with spermatogonia, spermatocytes, early spermatids, late spermatids and somatic cells, respectively. Transcripts in the somatic cell cluster showed large changes in expression pi, mainly caused by changes in cellularity. Further investigations revealed that the low dose irradiation seemed to cause Leydig cell hyperplasia, which contributed to the detected expression changes in the somatic cell cluster.ConclusionsThe five clusters represent gene expression in distinct cell types of the adult testis. We observed large expression changes in the somatic cell profile, which mainly could be attributed to changes in cellularity, but hyperplasia of Leydig cells may also play a role. We speculate that the possible hyperplasia may be caused by lower testosterone production and inadequate inhibin signalling due to missing germ cells.

Wigwams: identifying gene modules co-regulated across multiple biological conditions

“…Time series experiments are often used to examine the dynamics of gene expression ( Belling et al , 2013 ; Windram et al , 2012 ), and with the decreasing cost of profiling techniques, more datasets covering multiple time series showing how an organism responds to different conditions are becoming available. Such data offer the opportunity to study shared regulatory mechanisms that are used to regulate genes under more than one condition.…”

A Testis-Specific Long Noncoding RNA, Start, Is a Regulator of Steroidogenesis in Mouse Leydig Cells

“…In contrast, no significant change was observed in interstitial cells between KO and wild-type mice at 2.5 months of age ( Figure 8B ). Since interstitial cells mainly consist of Leydig cells but also contain small populations of other types of cells ( 59 , 60 ), we investigated by immunohistochemistry of HSD3B, a marker of Leydig cells ( 61 , 62 ), whether the altered number of interstitial cells reflected the Leydig cell population. The number of HSD3B-positive cells was significantly decreased in Start -KO testes at 8 dpp, while it was not altered at 2.5 months of age ( Figure 8C ).…”

Low-Dose Radiation Exposure with 56MnO2 Powder Changes Gene Expressions in the Testes and the Prostate in Rats

“…Another study in SD rats evaluating the testicular toxicity of Icariin identified the specific changes in mRNA expressions, including steroidogenesis-related genes and Sertoli cell-specific genes in the testes, where no histopathological alterations were found [ 12 ]. More systematic profiling of transcriptome in the testes after irradiation was reported in mice locally exposed to 1 Gy of X-radiation [ 17 ]. The authors found five clusters of gene expression changes that could be associated with alterations of germ cells and somatic cells.…”