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.
Highlights
Radiotherapy is used routinely to treat testicular cancer
Clusters of transcripts affected by low dose irradiation Gene expression profiling was performed on total RNA from mice testis (n = 17) from a time series following low dose irradiation (1 Gy)
These transcripts all had expression profiles during the time series that potentially were caused by the recovery from irradiation, i.e. transcripts with large overall expression changes during the time series, but small expression changes between neighbouring time points
Summary
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. Cells in the testis display different radio-sensitivity and the degree of radiation-induced damage depends on dose and fractionation of the radiation [1]. Human Leydig cells are damaged by the irradiation doses used to treat testicular cancer patients (16–20 Gy) [1,6,7], in many cases the testosterone production is maintained. Rodent Leydig cells have shown dysfunction after high dose irradiation (5 Gy) leading to low testosterone and increased serum luteinizing hormone (LH) levels [8]. It has been reported that rodent Sertoli cells are affected by high dose irradiation (5 Gy) [9]
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