Specific expression and alternative splicing of mouse genes during spermatogenesis

Li, Qun; Li, Tongtong; Xiao, Xia; Ahmad, Dawood Warraich; Zhang, Ning; Li, Hao; Chen, Zi-Yu; Hou, Junyao; Liao, Mingzhi

doi:10.1039/c9mo00163h

Cited by 8 publications

(9 citation statements)

References 49 publications

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“…While these genes have not been previously studied in spermatogenesis, scRNAseq data confirmed their expression in germ cell development. Surprisingly, while abundant expression of lincRNAs and alternatively spliced RNAs has been described for the testes, the use of alternative promoters during spermatogenesis has not been studied in mammals 91, 92 . In Drosophila , the transition from proliferating spermatogonia to differentiating spermatocytes is accompanied by dramatic change in transcription, with about a third of new transcripts originating from alternative promoters 93 .…”

Section: Discussionmentioning

confidence: 99%

TET1 Catalytic Activity is Required for Reprogramming of Imprinting Control Regions and Patterning of Sperm-Specific Hypomethylated Regions

Prasasya

Caldwell

Liu

et al. 2023

Preprint

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DNA methylation erasure is required for mammalian primordial germ cell reprogramming. TET enzymes iteratively oxidize 5-methylcytosine to generate 5-hyroxymethylcytosine (5hmC), 5-formylcytosine, and 5-carboxycytosine to facilitate active genome demethylation. Whether these bases are required to promote replication-coupled dilution or activate base excision repair during germline reprogramming remains unresolved due to the lack of genetic models that decouple TET activities. Here, we generated two mouse lines expressing catalytically inactive TET1 (Tet1-HxD) and TET1 that stalls oxidation at 5hmC (Tet1-V).Tet1-/-,Tet1V/V, andTet1HxD/HxDsperm methylomes show that TET1Vand TET1HxDrescue mostTet1-/-hypermethylated regions, demonstrating the importance of TET1&#39s extra-catalytic functions. Imprinted regions, in contrast, require iterative oxidation. We further reveal a broader class of hypermethylated regions in sperm of Tet1 mutant mice that are excluded from de novo methylation during male germline development and depend on TET oxidation for reprogramming. Our study underscores the link between TET1-mediated demethylation during reprogramming and sperm methylome patterning.

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Section: Discussionmentioning

confidence: 99%

TET1 Catalytic Activity is Required for Reprogramming of Imprinting Control Regions and Patterning of Sperm-Specific Hypomethylated Regions

Prasasya

Caldwell

Liu

et al. 2023

Preprint

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“…Spliceosome. During spermatogenesis, the transcriptionally active germ-cell stages are the mitotic and meiotic stages and alternative splicing controls the temporally specific use of transcripts required for spermiogenesis 82 including, in partic- ular, meiotic intron-retaining transcripts mechanisms. 60 Eightyfour factors involved in the spliceosome pathway were found in the present analysis with a large majority of proteins showing a higher abundance in zone A (Figure 8).…”

Section: Enriched Pathwaysmentioning

confidence: 99%

“…However, a study of glomerular transcriptomes in patients has revealed that up-regulated genes in FSGS were involved in, among other things, spermatogenesis and gamete generation, and related for example to cell cycle and proliferation, TGF-β superfamily signaling and RNA process-80 Cluster 5 appeared to be characterized by translation and mRNA processing, including mRNA splicing, in all of the five biological categories, which is in accordance with the fact that factors controlling spermatogenesis are controlled at transcriptional and post-transcriptional levels, resulting in male germ cells expressing the widest array of transcript variants. 59,60,81,82 According to the heatmap profile of cluster 5, actors in mRNA processing exhibit a higher expression level in the zone of cysts with spermatogonia, then levels decreased during spermatogenesis to be at the lowest in the zone of late spermatids.…”

Section: Variations In Protein Levels During Spermatogenesismentioning

confidence: 99%

Comparative Proteome Analysis of Four Stages of Spermatogenesis in the Small-Spotted Catshark (Scyliorhinus canicula), Using High-Resolution NanoLC-ESI-MS/MS

Jeanne,

Bernay,

Sourdaine

2023

J. Proteome Res.

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Spermatogenesis is a highly specialized process of cell proliferation and differentiation leading to the production of spermatozoa from spermatogonial stem cells. Due to its testicular anatomy, Scyliorhinus canicula is an interesting model to explore stage-based changes in proteins during spermatogenesis. The proteomes of four testicular zones corresponding to the germinative niche and to spermatocysts (cysts) with spermatogonia (zone A), cysts with spermatocytes (zone B), cysts with young spermatids (zone C), and cysts with late spermatids (zone D) have been analyzed by nanoLC-ESI-MS/MS. Gene ontology and KEGG annotations were also performed. A total of 3346 multiple protein groups were identified. Zone-specific protein analyses highlighted RNA-processing, chromosome-related processes, cilium organization, and cilium activity in zones A, D, C, and D, respectively. Analyses of proteins with zone-dependent abundance revealed processes related to cellular stress, ubiquitin-dependent degradation by the proteasome, post-transcriptional regulation, and regulation of cellular homeostasis. Our results also suggest that the roles of some proteins, such as ceruloplasmin, optineurin, the pregnancy zone protein, PA28β or the Culling-RING ligase 5 complex, as well as some uncharacterized proteins, during spermatogenesis could be further explored. Finally, the study of this shark species allows one to integrate these data in an evolutionary context of the regulation of spermatogenesis. Mass spectrometry data are freely accessible via iProX-integrated Proteome resources () for reuse purposes.

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“…PTBP1 is highly expressed in spermatogonia during mitosis, while PTBP2 is significantly upregulated during spermatocyte meiosis. Abnormal changes in these two genes can lead to abnormal spermatogenesis [60,61]. For the first time, we have identified in human spermatozoa samples a splice variant of DDX46, a key gene in reproductive function regulation, which is generally thought to affect type I interferons and related pro-inflammatory cytokines by recruiting m6A "eraser" ALKBH5 [62,63].…”

Section: Frequent Alternative Splicing Events Especially Exon Skippingmentioning

confidence: 99%

Epigenetic Alterations in Cryopreserved Human Spermatozoa: Suspected Potential Functional Defects

Wang

Todorov

Cheng

et al. 2022

Cells

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Background: Gene set enrichment analysis (GSEA) was conducted on raw data, and alternative splicing (AS) events were found after mRNA sequencing of human spermatozoa. In this study, we aimed to compare unknown micro-epigenetics alternations in fresh and cryopreserved spermatozoa to evaluate the effectivity of cryopreservation protocols. Methods: Spermatozoa were divided into three groups: fresh spermatozoa (group 1), cryoprotectant-free vitrified spermatozoa (group 2), and conventionally frozen spermatozoa (group 3). Nine RNA samples (three replicates in each group) were detected and were used for library preparation with an Illumina compatible kit and sequencing by the Illumina platform. Results: Three Gene Ontology (GO) terms were found to be enriched in vitrified spermatozoa compared with fresh spermatozoa: mitochondrial tRNA aminoacylation, ATP-dependent microtubule motor activity, and male meiotic nuclear division. In alternative splicing analysis, a number of unknown AS events were found, including functional gene exon skipping (SE), alternative 5′ splice sites (A5SS), alternative 3′ splice sites (A3SS), mutually exclusive exon (MXE), and retained intron (RI). Conclusions: Cryopreservation of spermatozoa from some patients can agitate epigenetic instability, including increased alternative splicing events and changes in crucial mitochondrial functional activities. For fertilization of oocytes, for such patients, it is recommended to use fresh spermatozoa whenever possible; cryopreservation of sperm is recommended to be used only in uncontested situations.

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Specific expression and alternative splicing of mouse genes during spermatogenesis

Abstract: Considering the high abundance of spliced RNAs in testis compared to other tissues, it is needed to construct the landscape of alternative splicing during spermatogenesis.

Cited by 8 publications

References 49 publications

TET1 Catalytic Activity is Required for Reprogramming of Imprinting Control Regions and Patterning of Sperm-Specific Hypomethylated Regions

TET1 Catalytic Activity is Required for Reprogramming of Imprinting Control Regions and Patterning of Sperm-Specific Hypomethylated Regions

Comparative Proteome Analysis of Four Stages of Spermatogenesis in the Small-Spotted Catshark (Scyliorhinus canicula), Using High-Resolution NanoLC-ESI-MS/MS

Epigenetic Alterations in Cryopreserved Human Spermatozoa: Suspected Potential Functional Defects

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