Short-term exposure of sleep deprivation male model rats to dutasteride promotes the discovery of gene profiles related to fertility impairments.

backgroundFertility was impaired in sleep deprivation (SD) male rats. Dutasteride (DUT), a 5-α reductase inhibitor, also had negative effects on fertility, however, its definite mechanisms were still unknown. To this end, SD male model rats, exposed to DUT for a short period of time, were used to observe whether DUT would exacerbate fertility damage and further to explore the possible mechanism of its fertility damage effects.

methodsMale rats were randomly divided into 3 groups: Model control (MC) group and the two model groups (i.e. SD group and DUT group). For model groups, the modified multi-platform method was used to model SD for 42 consecutive days. The rats in DUT group were administered by gavage at DUT doses of 20 mg-kg− 1 for 21 consecutive days. Whether the short-term administration of DUT would bring the aforesaid rats about fertility damage was confirmed by observing rats’ behavioral changes, detecting serum testosterone levels, testing sperm-related parameters, and pathological analysis of testicular and epididymal tissue changes. RNA sequencing (RNA-seq) was applied to explore the overall transcriptional profile of genes related to DUT-induced exacerbation of fertility impairment in SD model male rats. By analyzing the differentially expressed genes (DEGs) profiles among those groups, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were used to explore the gene profile associated with DUT promoting fertility impairments and further to find the mechanism of common fertility damages between SD and DUT. Finally, the transcription of key genes was verified by quantitative reverse transcription polymerase chain reaction (qRT-PCR). This experimental work was carried out in 2023–2024.

resultsAfter exposure to DUT, the rats had significantly changed sperm-related parameters and showed further aggravated gonadal tissue damage. Compared with the model control, the SD rats had 445 DEGs. And compared with the SD group, the DUT group had 477 DEGs. Ibsp, Runx1, Fgf18, Areg, Stat6, Mapk3, and Gng4 were screened as the hub genes by Cytohubba. 142 cross-DEGs were identified. Notably, Abca5 expression was continuously decreased in this exposure process. In the cross-DEGs, ABCA5 interacted indirectly with LOR, SLC22A2, PCARE and RCVRN by its family proteins.

conclusionsShort-term exposure to DUT aggravated the fertility impairment of SD rats and unique actions on the aforesaid hub genes might be one of the possible reasons. The 142 common fertility-impairing DEGs involved in immunological, neurological and metabolic aspects. The abnormal expression of Abca5 and its indirectly associated other cross-DEGs might be the important gene targets for fertility disorders in male rats.