Abstract
The cannabinoid receptor CB1 regulates differentiation of spermatids. We recently characterized spermatozoa from caput epididymis of CB1-knock-out mice and identified a considerable number of sperm cells with chromatin abnormality such as elevated histone content and poorly condensed chromatin. In this paper, we extended our findings and studied the role of CB1 in the epididymal phase of chromatin condensation of spermatozoa by analysis of spermatozoa from caput and cauda epididymis of wild-type and CB1-knock-out mouse in both a homozygous or heterozygous condition. Furthermore, we studied the impact of CB1-gene deletion on histone displacement mechanism by taking into account the hyperacetylation of histone H4 and players of displacement such as Chromodomain Y Like protein (CDYL) and Bromodomain testis-specific protein (BRDT). Our results show that CB1, via local and/or endocrine cell-to-cell signaling, modulates chromatin remodeling mechanisms that orchestrate a nuclear condensation extent of mature spermatozoa. We show that CB1-gene deletion affects the epididymal phase of chromatin condensation by interfering with inter-/intra-protamine disulphide bridges formation, and deranges the efficiency of histone removal by reducing the hyper-acetylation of histone H4. This effect is independent by gene expression of Cdyl and Brdt mRNA. Our results reveal a novel and important role for CB1 in sperm chromatin condensation mechanisms.
Highlights
Spermiogenesis is the terminal differentiation phase of spermatogenesis by which round spermatids (SPTs) undergo impressive histomorphological changes that facilitate development of mature and elongated cells carrying tightly condensed chromatin and nuclei, namely mature SPTs or spermatozoa (SPZs)
We studied the impact of CB1-gene deletion on histone displacement mechanism by taking into account the hyperacetylation of histone H4 and players of displacement such as Chromodomain Y Like protein (CDYL) and Bromodomain testis-specific protein (BRDT)
We show that CB1-gene deletion affects the epididymal phase of chromatin condensation by interfering with inter-/intra-protamine disulphide bridges formation, and deranges the efficiency of histone removal by reducing the hyper-acetylation of histone H4
Summary
Spermiogenesis is the terminal differentiation phase of spermatogenesis by which round spermatids (SPTs) undergo impressive histomorphological changes that facilitate development of mature and elongated cells carrying tightly condensed chromatin and nuclei, namely mature SPTs or spermatozoa (SPZs). Chromatin condensation extent of mature SPZs is orchestrated by testicular and epididymal events. These require chromatin remodeling mechanisms such as histone displacement/protamination and inter/intra-protamine disulphide bonds formation, respectively [2]. Nuclear condensation is mainly related to i) haploid expression of transition proteins (TNP1 and TNP2) and protamines, ii) histone post-translational modifications (PTMs) and displacement, and iii) histone-to-protamine exchange and DNA packaging [3,4,5,6]. In the Cdyl transgenic mouse model, the overexpression of CDYL decreases histone Kcr in elongating SPTs and interferes with histone displacement, which reveals a key role of CDYL in spermiogenesis as a modulator of histone PTMs with functional implications in histone removal mechanism [10]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
