ArticleStem cell research & therapy2025
Histone hyperacetylation disrupts spermatogonial stem cells homeostasis and impairs spermiogenesis.
Article in Stem cell research & therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2 citing papers in PubMed.
- Cellular senescence and aging: molecular mechanisms and convergent pathways.Cellular and molecular life sciences : CMLS · 2026Review
- Transcriptomic analysis reveals immune dysregulation and identifies key genes in ICU patients with severe ARDS.Frontiers in immunology · 2026Article
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9 authors.
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Abstract
backgroundIt is well-known that epigenetic regulation is involved in the negative effects of environmental physical, chemical and biological factors exposures on organs. To investigate the effects and mechanisms of histone hyperacetylation caused by environmental stress on spermatogenesis, we used the histone deacetylase inhibitor Panobinostat (PANO) to establish the hyperacetylation models in mice.
methodsTo investigate the effects of PANO on testicular function of male reproductive system, we conducted the evaluation of sperm quality parameters in mice. The morphological changes of testes were observed through hematoxylin and eosin (H&E) staining on paraffin sections and quantified by stereological measurements after treatment to explore the cause of infertility and figure out if PANO has any effect on the reproductive system of male mice. Immunofluorescence, immunohistochemistry and immunoblotting were utilized to elucidate the impact and mechanisms of PANO treatment on spermatogenesis. RNA-seq analysis was performed on mouse testes to elucidate the underlying mechanisms of PANO.
resultsThe rates of sperm survival and movement were reduced while malformation rate of sperm increased in the 34.4-day PANO group. Gene Set Enrichment Analysis (GSEA) supported the significant role of PANO in modulating cilium movement, sperm axoneme assembly and flagellated sperm motility. Numbers of MVH
conclusionsWe have reported that PANO exerts a negative impact on the spermatogonial stem cell pool in mouse testes by disrupting its niche. This disruption leads to a reduction in germ cell numbers and impairs sperm function in mice, ultimately resulting in infertility. Moreover, PANO destabilizes the nucleosomes by increasing the transcriptional levels of H2bc4 and H1f2, affects the histone-to-protamine transition, and arrests spermiogenesis at the elongating spermatid stage. These findings also suggest that H2bc4 and H1f2 may be potential key biomarkers in the testis for diagnosing male infertility associated with aberrant histone hyperacetylation due to the exposure of environmental pollutants.
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