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PRDM Histone Methyltransferase mRNA Levels Increase in Response to Curative Hormone Treatment for Cryptorchidism-Dependent Male Infertility

机译:PRDM组蛋白甲基转移酶mRNA水平响应隐睾依赖性男性不育症的治疗性激素治疗增加

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There is a correlation between cryptorchidism and an increased risk of testicular cancer and infertility. During orchidopexy, testicular biopsies are performed to confirm the presence of type A dark (Ad) spermatogonia, which are a marker for low infertility risk (LIR). The Ad spermatogonia are absent in high infertility risk (HIR) patients, who are treated with a gonadotropin-releasing hormone agonist (GnRHa) to significantly lower the risk of infertility. Despite its prevalence, little is known about the molecular events involved in cryptorchidism. Previously, we compared the transcriptomes of LIR versus HIR patients treated with and without hormones. Here, we interpreted data regarding members of the positive regulatory domain-containing ( PRDM ) family; some of which encoded histone methyltransferases that are important for reproduction. We found there were lower levels of PRDM1 , PRDM6 , PRDM9 , PRDM13 , and PRDM14 mRNA in the testes of HIR patients compared with LIR patients, and that PRDM7, PRDM9 , PRDM12 , and PRDM16 were significantly induced after GnRHa treatment. Furthermore, we observed PRDM9 protein staining in the cytoplasm of germ cells in the testes from LIR and HIR patients, indicating that the mRNA and protein levels corresponded. This result indicated that the curative hormonal therapy for cryptorchidism involved conserved chromatin modification enzymes.
机译:隐睾症与睾丸癌和不育症风险增加之间存在相关性。在兰科手术期间,进行睾丸活检以确认是否存在A型深色(Ad)精原细胞,这是低不孕风险(LIR)的标志。高精子不育风险(HIR)患者不使用Ad精原细胞,这些患者接受促性腺激素释放激素激动剂(GnRHa)治疗可显着降低不孕风险。尽管它很盛行,但对于隐睾症涉及的分子事件知之甚少。以前,我们比较了使用和不使用激素治疗的LIR和HIR患者的转录组。在这里,我们解释了有关正调控域(PRDM)家族成员的数据。其中一些编码对再生很重要的组蛋白甲基转移酶。我们发现HIR患者的睾丸中PRDM1,PRDM6,PRDM9,PRDM13和PRDM14 mRNA的水平低于LIR患者,并且在GnRHa治疗后显着诱导了PRDM7,PRDM9,PRDM12和PRDM16。此外,我们在LIR和HIR患者的睾丸中观察到生殖细胞胞质中的PRDM9蛋白染色,表明mRNA和蛋白水平相对应。该结果表明治疗隐睾的激素治疗涉及保守的染色质修饰酶。

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