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Loss of circSry leads to decreased γH2AX levels and impairs spermatogenesis

ABSTRACT: Loss of circSry leads to decreased γH2AX levels and impairs spermatogenesis

PROVIDER: PRJNA813151 | ENA |

REPOSITORIES: ENA

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Loss of circSry leads to decreased γH2AX levels and impairs spermatogenesis

Project description:Purpose:To gain a deeper insight into how circSry regulates spermatogenesis in spermatocytes, RNA-sequencing (RNA-seq) was performed to analyze the genome-wide changes by circSry deletion.

2022-03-08 | GSE197971 | GEO

CircSry regulates spermatogenesis by enhancing γH2AX expression via sponging miR138-5p

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CircSry regulates spermatogenesis by enhancing γH2AX expression via sponging miR138-5p

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Dysfunction of CEP128 impairs spermatogenesis but not ciliogenesis in humans and mice

Project description:The centrosome is a conserved eukaryotic organelle essential for reproductive process, and centrosomal proteins (CEP) are necessary for composition of the centrosome. However, few CEPs have been genetically linked to fertility, and the related molecular mechanisms remains mysterious. Here, we identified a new CEP, CEP128, which is functional in spermatogenesis, fertilization and embryonic development in both humans and mice. The variants of CEP128/Cep128 could lead to aberrant centrosome structures of the sperm inducing to anomalies in sperm morphology, count as well as motility, and further result in male infertility, but did not grossly affect ciliogenesis. Mechanistically, both loss and up-regulation of CEP128 could cause suppressed expressions of the genes involved in the spermatogenesis and fertilization phase. Altogether, our findings unprecedentedly unveil a crucial role of CEP128 in male fertility and provides new insight into the function of CEPs in human disease.

2022-05-19 | PXD022731 | Pride

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Genome wide profiling of the RNAPII, γH2AX, H3K4Me1, H3K4M2 and H3K4Me3 in MLL2 F/F and FC/FC MEF cells

Project description:We investigated the RNAPII and γH2AX occupancy genome wide by ChIP-Seq in MLL2 F/F and FC/FC80 MEF cells. We found that a week after MLL2 excision (FC/FC cells), a group of genes present higher levels of γH2AX and RNAPII near the TSS, as compared to the control (F/F cells). H3K4Me1, H3K4M2 and H3K4Me3 levels near the TSS were also studied.

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Zika virus disrupts steroidogenesis and impairs spermatogenesis by stalling the translation of CYP17A1 mRNA

Project description:ZIKV infection is associated with testicular damage and abnormal spermatogenesis. However, the molecular mechanisms underlying these pathogenic processes remain unclear. Here, we demonstrate that ZIKV disrupts Leydig cells' ability to produce testosterone, leading to decreased sperm counts and motility. Specifically, the non-structural protein NS2A of ZIKV downregulates testosterone production by directly binding to mRNA of CYP17A1, a key enzyme in testosterone synthesis, thereby inhibiting its translation. Notably, the sole membrane-traversing segment and its flanking loops of NS2A are crucial for this interaction with CYP17A1 mRNA. Scanning mutagenesis studies within this sequence identified amino acid residues critical for NS2A binding and the suppression of CYP17A1 mRNA translation. Testicular inoculation of adeno-associated virus (AAV) delivering ZIKV-NS2A or its mutant showed that ZIKV-NS2A alone is sufficient to affect steroidogenesis and spermatogenesis in vivo. Moreover, a mutant virus generated by reverse genetics, containing a single amino acid mutation that abolishes NS2A’s binding to CYP17A1 mRNA, exhibited significantly lower inhibition of steroidogenesis and spermatogenesis compared to the wild-type virus in mouse models. These findings enhance our understanding of how ZIKV impacts male reproductive health and provide crucial insights for future preventive and therapeutic strategies.

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