ArticleCell & bioscience2022
PA1 participates in the maintenance of blood-testis barrier integrity via cooperation with JUN in the Sertoli cells of mice.
Article in Cell & bioscience, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 13 citations in OpenAlex.
- JUND-driven stress-responsive astrocytes promote neuronal apoptosis via enhanced gap junction signaling in autism spectrum disorder.Molecular autism · 2026Article
- Sry-modified laboratory rat lines to study sex-chromosome effects underlying sex differences in physiology and disease: Four Core Genotypes and more.Biology of sex differences · 2026Article
- Single-nucleus multiomics of murine gonads reveals transcriptional regulatory network underlying supporting lineage differentiation.Science advances · 2026Article
- Cut&tag: a powerful epigenetic tool for chromatin profiling.Epigenetics · 2024Review
- DCAF2 regulates the proliferation and differentiation of mouse progenitor spermatogonia by targeting p21 and thymine DNA glycosylase.Cell proliferation · 2024Article
- A tissue specific-infection mouse model of SARS-CoV-2.Cell discovery · 2023Article
- PTIP-Associated Protein 1: More Than a Component of the MLL3/4 Complex.Frontiers in genetics · 2022Review
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundThe blood-testis barrier (BTB) is essential to the microenvironment of spermatogenesis, and Sertoli cells provide the cellular basis for BTB construction. Numerous nuclear transcription factors have been identified to be vital for the proper functioning of Sertoli cells. PA1 has been reported to play important roles during diverse biological processes, yet its potential function in male reproduction is still unknown.
resultsHere, we show that PA1 was highly expressed in human and mouse testis and predominantly localized in the nuclei of Sertoli cells. Sertoli cell-specific Pa1 knockout resulted in an azoospermia-like phenotype in mice. The knockout of this gene led to multiple defects in spermatogenesis, such as the disorganization of the cytoskeleton during basal and apical ectoplasmic specialization and the disruption of the BTB. Further transcriptomic analysis, together with Cut-Tag results of PA1 in Sertoli cells, revealed that PA1 could affect the expression of a subset of genes that are essential for the normal function of Sertoli cells, including those genes associated with actin organization and cellular junctions such as Connexin43 (Cx43). We further demonstrated that the expression of Cx43 depended on the interaction between JUN, one of the AP-1 complex transcription factors, and PA1.
conclusionOverall, our findings reveal that PA1 is essential for the maintenance of BTB integrity in Sertoli cells and regulates BTB construction-related gene expression via transcription factors. Thus, this newly discovered mechanism in Sertoli cells provides a potential diagnostic or even therapeutic target for some individuals with azoospermia.
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