Transcriptome analyses reveal the fertility defect in the Dp(16)1Yey/+ mouse model of Down syndrome.

PURPOSE: To explore the molecular mechanisms underlying male reproductive defects in Down syndrome (DS) by analyzing the transcriptomic characteristics of testis tissue in the DS mouse model.

METHODS

In this study, we used Dp(16)1Yey/ + (hereafter called Dp16) mice as a DS model. The morphological features were assessed by H&E staining, PAS staining, and transmission electron microscopy in the testicular and epididymal tissues of Dp16 and normal mice. Sperm were diluted for microscopic observation. Sperm count, motility, abnormal sperm proportion, and parameters like VAP, VSL, and VCL were evaluated. Mitochondrial membrane potential was assessed with the JC-1 fluorescent probe using flow cytometry. In addition, to evaluate the reproductive ability of male Dp16 mice, adult male Dp16 mice and female WT mice were caged in a 1:1 ratio, and IVF was performed. Further RNA-seq sequencing was performed on Dp16 mice testis tissue and compared with normal mice.

RESULTS

We found that they also exhibited similar phenomena as individuals with DS, such as decreased sperm count and abnormal morphology. RNA-seq sequencing was performed to compare the testis tissues of Dp16 mice with normal mice. The results showed that there were many differentially expressed genes in Dp16 mouse testis, involving signaling pathways related to spermatogenesis, testis development, and hormone synthesis. In addition, many genes in Dp16 mouse testis were associated with non-obstructive azoospermia and Klinefelter syndrome, suggesting that these diseases may have common pathogenic genes.

CONCLUSIONS

This study systematically revealed the transcriptomic characteristics of DS model mouse testis tissue, uncovering key genes and pathways involved in male fertility defects. The findings provide clues to understanding how chromosomal abnormalities affect fertility and a scientific basis for developing new strategies for treating DS.