Transcriptome analysis of the epididymis from Plag1 deficient mice suggests dysregulation of sperm maturation and extracellular matrix genes

Abstract

Background: The transcription factor pleomorphic adenoma gene 1 (PLAG1) is required for male fertility. Mice deficient in PLAG1 exhibit decreased sperm motility and abnormal epididymal tubule elongation and coiling, indicating impaired sperm maturation during epididymal transit. However, the downstream transcriptomic profile of the Plag1 knockout (KO; Plag1 −/−) murine epididymis is currently unknown. Results: In this study, the PLAG1-dependent epididymal transcriptome was characterised using RNA sequencing. Several genes important for the control of sperm maturation, motility, capacitation and the acrosome reaction were dysregulated in Plag1 −/− mice. Surprisingly, several cell proliferation genes were upregulated, and Ki67 analysis indicated that cell proliferation is aberrantly upregulated in the cauda epididymis stroma of Plag1 −/− mice. Gene ontology analysis showed an overall upregulation of genes encoding extracellular matrix components, and an overall downregulation of genes encoding metalloendopeptidases in the epididymides from Plag1 −/− mice. Conclusion: Together, these results suggest a defect in the epididymal extracellular matrix in Plag1 −/− mice. These results imply that in addition to maintaining epididymal integrity directly, PLAG1 may also regulate several genes involved in the regulation of sperm maturation and capacitation. Moreover, PLAG1 may also be involved in regulating tissue homeostasis and ensuring proper structure and maintenance of the extracellular matrix in the epididymis.

PLAG1 dampens protein synthesis to promote human hematopoietic stem cell self-renewal

“…Ectopic PLAG1-S significantly altered the expression of 543 genes (supplemental Table 4; Figure 4C ). Consistent with its understood function as a transcription activator, 60% of the 291 upregulated genes are proximally bound by PLAG1-S. Thirty percent of downregulated genes are also directly bound, which similarly to other recent publications, 60 suggests an underappreciated role for PLAG1-S in negative regulation of gene expression. Gene set enrichment analysis (GSEA) revealed that coordinated pathway-level changes are dominated by negative enrichments (supplemental Table 6).…”

The significance of single-cell transcriptome analysis in epididymis research

“…With the advancement of sequencing technologies ( Wong et al, 2020 ; Wu et al, 2021a ; Zhao et al, 2021a ; Liu et al, 2022b ), a greater understanding of the molecular mechanisms underlying epididymal function has been achieved. The significance of the epididymis in male reproductive biology has garnered increasing attention.…”

Identification of postnatal development dependent genes and proteins in porcine epididymis

“…Consistently, the dynamic alterations of the gonadal extracellular matrix have been observed from puberty stage to sexual mature stage [ 22 , 23 ]. Since the extracellular matrix is a reservoir for growth factors and bioactive molecules that orchestrate cell signaling, functions, properties, and morphology, it is naturally considered as a key player in modulating epididymal tissue homeostasis and sperm maturation [ 24 , 25 ]. Some DEGs not only affect extracellular matrix construction but also associate with sperm physiological function were found (Fig.…”