Circ-CREBBP inhibits sperm apoptosis via the PI3K-Akt signaling pathway by sponging miR-10384 and miR-143-3p

Ding, Ning; Huang, Mengna; Liu, Jianfeng; Wang, Chonglong; Zhang, Chun; Cao, Jinkang; Zhang, Qin; Jiang, Li

doi:10.1038/s42003-022-04263-2

Cited by 7 publications

(4 citation statements)

References 73 publications

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“…We further predicted the function of the differentially expressed miRNAs in the top 100 and found that these miRNAs (miR-143-3p, miR-152-3p, miR-378a-3p and miR-92a-3p) were related to cell cycle or meiosis. miR-143-3p [68], miR-152-3p [69], miR-378a-3p [70] and miR-92a-3p [71,72] have also been reported to be involved in the regulation of spermatogenesis or semen quality. It is interesting that there is no significant difference in the miRNAs (miR-20, miR-21 and miR-106a) involved in the self-renewal of spermatogonial stem cells [46], indicating that testicular heat stress under the conditions of this study has little effect on spermatogonial stem cells and they have good recovery ability after testicular heat stress injury.…”

Section: Discussionmentioning

confidence: 99%

Potential Function of Testicular MicroRNAs in Heat-Stress-Induced Spermatogenesis Disorders

Gan

Xie

et al. 2023

IJMS

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Spermatogenesis is temperature-dependent, and the increase in testicular temperature seriously affects mammalian spermatogenesis and semen quality. In this study, the testicular heat stress model of mice was made with a 43 °C water bath for 25 min, and the effects of heat stress on semen quality and spermatogenesis-related regulators were analyzed. On the 7th day after heat stress, testis weight shrank to 68.45% and sperm density dropped to 33.20%. High-throughput sequencing analysis showed that 98 microRNAs (miRNAs) and 369 mRNAs were down-regulated, while 77 miRNAs and 1424 mRNAs were up-regulated after heat stress. Through gene ontology (GO) analysis of differentially expressed genes and miRNA–mRNA co-expression networks, it was found that heat stress may be involved in the regulation of testicular atrophy and spermatogenesis disorders by affecting cell meiosis process and cell cycle. In addition, through functional enrichment analysis, co-expression regulatory network, correlation analysis and in vitro experiment, it was found that miR-143-3p may be a representative potential key regulatory factor affecting spermatogenesis under heat stress. In summary, our results enrich the understanding of miRNAs in testicular heat stress and provide a reference for the prevention and treatment of heat-stress-induced spermatogenesis disorders.

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Section: Discussionmentioning

confidence: 99%

Potential Function of Testicular MicroRNAs in Heat-Stress-Induced Spermatogenesis Disorders

Gan

Xie

et al. 2023

IJMS

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“…The PI3K-Akt, MAPK, and Ras signalling pathways are involved in embryonic development. Ding et al [18] discovered that circCREBBP targets miR-143-3p and promotes boar sperm survival and vitality through the PI3K-Akt signalling pathway. Zhao et al [19] revealed that high melatonin levels may induce cell apoptosis, arrest the cell cycle, and inhibit cell growth through the PI3K-AKT signalling pathway, thus interfering with rat embryonic heart development.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis and validation of differentially expressed miRNA in the sperm of partners of patients with unexplained recurrent miscarriages

Tian,

Zhao

2024

Preprint

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Background: Recurrent miscarriage is a common multifactorial disease, and even after systematic examination, the cause of the miscarriages cannot be determined in approximately 50% of patients. However, currently, few examinations are conducted for partners of patients with recurrent miscarriages. The contribution of spermatozoa to new individuals is not limited to half of the diploid genome. Recent studies have shown that spermatozoa add several components to oocytes, including a complex RNA population that plays an important role in paternal chromatin packaging, sperm maturation and empowerment, fertilisation, early embryogenesis, and developmental maintenance. In view of this, we constructed a sperm miRNA expression profile of partners of patients with unexplained recurrent miscarriages and explored the relationship between unexplained recurrent miscarriages and differential miRNA expression in sperm. Methods: Semen samples were obtained from the partners of patients with unexplained recurrent miscarriages treated at the affiliated hospital of Inner Mongolia Medical University, as well as healthy men who underwent physical examinations between July 2021 and February 2023. The miRNA expression profiles of the sperm in the two groups were detected using high-throughput sequencing. Bioinformatics analysis of differentially expressed miRNAs was performed to predict target genes and their action pathways and verify the expression levels of paternal miRNAs in known embryos in the study and control groups through RT-PCR technology. Result: A total of 83 differentially expressed miRNAs were detected between the two groups, of which 39 were significantly upregulated and 44 were significantly downregulated. The results showed that spermatic hsa-miR-34c-5p, hsa-miR-1285-3p, hsa-miR-486-3p, and hsa-miR-146b-3p may regulate the occurrence of unexplained recurrence through the Ras, PI3K-Akt, and MAPK signalling pathways in the bioinformatics analysis. The expression of hsa-miR-34c-5 in spouses of patients with unexplained miscarriage recurrence was downregulated (p < 0.001). Binary logistic regression analysis showed that low expression of hsa-miR-34c-5p was a high-risk factor for recurrent miscarriage (odds ratio [OR] = 4.344; 95% confidence interval [CI], 1.11916.857; p < 0.05). Conclusion: The occurrence of unexplained recurrent miscarriages is associated with the differential expression of key miRNAs in the sperms of patients' spouses.

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“…These miRNAs exhibited good performance in discriminating patients with PCa from the controls. Moreover, we found that circ-CREBBP in SPEVs can regulate the expression of ssc-miR-143-3p and ssc-miR-10384 in sperm, as well as the expression of MCL1, CREB1, CREBBP, BAX, and CASP3, thereby affecting the apoptosis of sperm . Several studies have used proteomic techniques to detect proteins in SPEVs.…”

Section: Introductionmentioning

confidence: 92%

“…Moreover, we found that circ-CREBBP in SPEVs can regulate the expression of ssc-miR-143-3p and ssc-miR-10384 in sperm, as well as the expression of MCL1, CREB1, CREBBP, BAX, and CASP3, thereby affecting the apoptosis of sperm. 28 Several studies have used proteomic techniques to detect proteins in SPEVs. Yang et al identified 1,474 proteins in human seminal plasma exosomes, which were mainly involved in energy and metabolic pathways.…”

Section: ■ Introductionmentioning

confidence: 99%

Proteomics and Metabolic Characteristics of Boar Seminal Plasma Extracellular Vesicles Reveal Biomarker Candidates Related to Sperm Motility

Zhang,

Ding,

Cao

et al. 2024

J. Proteome Res.

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Although seminal plasma extracellular vesicles (SPEVs) play important roles in sperm function, little is known about their metabolite compositions and roles in sperm motility. Here, we performed metabolomics and proteomics analysis of boar SPEVs with high or low sperm motility to investigate specific biomarkers affecting sperm motility. In total, 140 proteins and 32 metabolites were obtained through differentially expressed analysis and weighted gene coexpression network analysis (WGCNA). Seven differentially expressed proteins (DEPs) (ADIRF, EPS8L1, PRCP, CD81, PTPRD, CSK, LOC100736569) and six differentially expressed metabolites (DEMs) (adenosine, beclomethasone, 1,2-benzenedicarboxylic acid, urea, 1-methyl-l-histidine, and palmitic acid) were also identified in WGCNA significant modules. Joint pathway analysis revealed that three DEPs (GART, ADCY7, and NTPCR) and two DEMs (urea and adenosine) were involved in purine metabolism. Our results suggested that there was significant correlation between proteins and metabolites, such as IL4I1 and urea (r = 0.86). Furthermore, we detected the expression level of GART, ADCY7, and CDC42 in sperm of two groups, which further verified the experimental results. This study revealed that several proteins and metabolites in SPEVs play important roles in sperm motility. Our results offered new insights into the complex mechanism of sperm motility and identified potential biomarkers for male reproductive diseases.

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Circ-CREBBP inhibits sperm apoptosis via the PI3K-Akt signaling pathway by sponging miR-10384 and miR-143-3p

Cited by 7 publications

References 73 publications

Potential Function of Testicular MicroRNAs in Heat-Stress-Induced Spermatogenesis Disorders

Potential Function of Testicular MicroRNAs in Heat-Stress-Induced Spermatogenesis Disorders

Bioinformatics analysis and validation of differentially expressed miRNA in the sperm of partners of patients with unexplained recurrent miscarriages

Proteomics and Metabolic Characteristics of Boar Seminal Plasma Extracellular Vesicles Reveal Biomarker Candidates Related to Sperm Motility

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