Association between RNA-binding protein Ptbp2 and germ cell injury in an experimentally-induced unilateral cryptorchidism murine model
Association between RNA-binding protein Ptbp2 and germ cell injury in an experimentally-induced unilateral cryptorchidism murine model
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RNA结合蛋白Ptbp2与实验诱导的单侧隐睾小鼠模型中生殖细胞损伤的关联
DOI：
10.1371/journal.pone.0186654
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发表时间：
2017-10-18
期刊：
影响因子：
3.7
通讯作者：
Zhang, Xiansheng
中科院分区：
文献类型：
--
作者：
Dou, Xianming;Gao, Jingjing;Zhang, Xiansheng
RNA结合蛋白多聚嘧啶束结合蛋白2（Ptbp2）作为男性生殖细胞发育的关键选择性剪接调节因子已被充分确立。然而，其在隐睾睾丸组织中的表达水平和作用尚未被探索。此外，热应激影响生殖细胞正确增殖和分化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诱导的睾丸组织生殖细胞损伤相关，我们使用了腹腔内隐睾手术的小鼠模型。在这里，我们提出了令人信服的证据表明，生殖细胞严重受损的小鼠单侧隐睾症，非梗阻性无精子症。Ptbp2和Pgk2 mRNA水平平行下降，提示Ptbp2水平与单侧隐睾小鼠模型生殖细胞损伤呈负相关。我们推测Ptbp2对热应激敏感，其破坏导致生殖细胞转录本Pgk2 mRNA稳定性下降，从而导致隐睾生殖细胞损伤。因此，我们确认Ptbp2是热应激诱导的精子细胞损伤和非梗阻性无精子症的一个重要因素。
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.