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Ptbp2 这种 RNA 结合蛋白与实验性单侧隐睾症小鼠模型中生殖细胞损伤的关系。

Association between RNA-binding protein Ptbp2 and germ cell injury in an experimentally-induced unilateral cryptorchidism murine model.

机构信息

Department of Urology, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.

Department of Urology, the Second Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, China.

出版信息

PLoS One. 2017 Oct 18;12(10):e0186654. doi: 10.1371/journal.pone.0186654. eCollection 2017.

Abstract

RNA binding protein polypyrimidine tract binding protein 2 (Ptbp2) as a key alternative splicing regulator for male germ cell development is well established. However, its expression levels and role in cryptorchidism testes tissues has not been explored. Additionally, the molecular mechanism of heat stress impacts the correct proliferation and differentiation of germ cells is unclear. To investigate whether changes in Ptbp2 expression are correlated with heat stress-induced germ cell injury in testicular tissue, we used a murine model of intraperitoneal cryptorchidism with surgical operation. Here we present compelling evidence that germ cells are severely damaged in mice with unilateral cryptorchidism, with non-obstructive azoospermia. And the Ptbp2 and Pgk2 mRNA levels were significantly decreased in parallel, leading us to conclude that the negative correlation between Ptbp2 levels and germ cell injury in unilateral cryptorchidism murine model. We hypothesize that Ptbp2 is susceptible to heat stress and its disruption has resulted in stability decline of germ cell transcripts Pgk2 mRNA, which consequently lead to germ cell injury in cryptorchidism testes. Thus, we confirm that Ptbp2 is an essential factor in heat stress-induced sperm cell injury and non-obstructive azoospermia.

摘要

RNA 结合蛋白多嘧啶 tract 结合蛋白 2(Ptbp2)作为雄性生殖细胞发育的关键可变剪接调控因子已得到充分证实。然而,其在隐睾症睾丸组织中的表达水平和作用尚未得到探索。此外,热应激对生殖细胞正确增殖和分化的影响的分子机制尚不清楚。为了研究 Ptbp2 表达的变化是否与热应激引起的睾丸组织生殖细胞损伤有关,我们使用了经手术的腹腔内隐睾症小鼠模型。在这里,我们提供了令人信服的证据表明,单侧隐睾症小鼠的生殖细胞受到严重损伤,出现非阻塞性无精子症。并且 Ptbp2 和 Pgk2 mRNA 水平也显著下降,这表明 Ptbp2 水平与单侧隐睾症小鼠模型中生殖细胞损伤之间存在负相关关系。我们假设 Ptbp2 易受热应激影响,其破坏导致生殖细胞转录本 Pgk2 mRNA 的稳定性下降,进而导致隐睾症睾丸中的生殖细胞损伤。因此,我们证实 Ptbp2 是热应激诱导的精子细胞损伤和非阻塞性无精子症的重要因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7088/5646856/5617d72eb5e0/pone.0186654.g001.jpg

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