关键词: ADAR BMP signaling Drosophila early spermatogenesis male infertility

Mesh : Animals Male Spermatogenesis / genetics Drosophila melanogaster / genetics metabolism Signal Transduction Drosophila Proteins / metabolism genetics Adenosine Deaminase / metabolism genetics Bone Morphogenetic Proteins / metabolism genetics Infertility, Male / genetics metabolism RNA-Binding Proteins / metabolism genetics Testis / metabolism

来  源:   DOI:10.3390/ijms25115643   PDF(Pubmed)

Abstract:
The dynamic process of Drosophila spermatogenesis involves asymmetric division, mitosis, and meiosis, which ultimately results in the production of mature spermatozoa. Disorders of spermatogenesis can lead to infertility in males. ADAR (adenosine deaminase acting on RNA) mutations in Drosophila cause male infertility, yet the causative factors remain unclear. In this study, immunofluorescence staining was employed to visualize endogenous ADAR proteins and assess protein levels via fluorescence-intensity analysis. In addition, the early differentiation disorders and homeostatic alterations during early spermatogenesis in the testes were examined through quantification of transit-amplifying region length, counting the number of GSCs (germline stem cells), and fertility experiments. Our findings suggest that deletion of ADAR causes testicular tip transit-amplifying cells to accumulate and become infertile in older male Drosophila. By overexpressing ADAR in early germline cells, male infertility can be partially rescued. Transcriptome analysis showed that ADAR maintained early spermatogenesis homeostasis through the bone-morphogenetic-protein (BMP) signaling pathway. Taken together, these findings have the potential to help explore the role of ADAR in early spermatogenesis.
摘要:
果蝇精子发生的动态过程涉及不对称分裂,有丝分裂,和减数分裂,最终导致成熟精子的产生。精子发生障碍可导致男性不育。果蝇中的ADAR(腺苷脱氨酶作用于RNA)突变会导致男性不育,然而,致病因素仍不清楚。在这项研究中,免疫荧光染色用于观察内源性ADAR蛋白,并通过荧光强度分析评估蛋白水平.此外,通过对转运放大区域长度的定量,检查了睾丸早期精子发生过程中的早期分化障碍和稳态改变,计数GSC(生殖干细胞)的数量,和生育实验。我们的发现表明,ADAR的缺失会导致睾丸尖端转运扩增细胞在老年雄性果蝇中积聚并变得不育。通过在早期生殖系细胞中过表达ADAR,男性不育可以部分救助。转录组分析表明,ADAR通过骨形态发生蛋白(BMP)信号通路维持早期精子发生稳态。一起来看,这些发现有可能有助于探索ADAR在早期精子发生中的作用。
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