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Altered expression of CYP17A1 and CYP19A1 in undescended testes of dogs with unilateral cryptorchidism.
Animal Genetics ( IF 1.8 ) Pub Date : 2020-07-13 , DOI: 10.1111/age.12977
P Krzeminska 1 , M Stachowiak 1 , M Skrzypski 2 , T Nowak 3 , A Maslak 4 , M Switonski 1
Affiliation  

Cryptorchidism is the most common disorder of sex development in dogs and testosterone plays a crucial role in the inguinal phase of the testes descending into the scrotum. The molecular background of impaired testosterone synthesis in the testes of cryptorchid dogs is poorly elucidated. In this study, we analyzed the expression of four genes involved in testicular steroidogenesis (CYP17A1, CYP19A1, HSD3B2 and HSD17B3) in undescended and contralateral scrotal testes from inguinal unilateral cryptorchid dogs (n = 13) and from the scrotal gonads of normal males (n = 15). We found that transcript level of CYP17A1 was significantly increased in inguinal gonads, while the level of CYP19A1 was decreased. For these two genes, we analyzed the methylation level of single CpG sites in the promoter region localized within putative target sites for testicular transcription factors (NUR77, CREB, CAR and HSF2). A correlation between decreased methylation in the promoter of CYP17A1 and its increased transcript level in undescended gonads was observed, but the change in protein level was not significant. We also resequenced the 5ʹ‐flanking region of both genes and two known polymorphic sites, SNP in CYP17A1 and an indel in CYP19A1, were found. However, the distribution of the variants in affected (n = 80) and control (n = 75) dogs was not associated with cryptorchidism. We tentatively conclude that the altered expression of CYP17A1 and CYP19A1 in undescended testes could be caused by their exposure to increased temperature in the body. Furthermore, we showed that the identified polymorphisms cannot be considered markers associated with a predisposition to cryptorchidism.

中文翻译:

CYP17A1和CYP19A1在单侧隐睾症狗的睾丸未降降中表达的改变。

隐睾症是狗中最常见的性发育障碍,睾丸激素在睾丸的腹股沟期下降到阴囊中起着至关重要的作用。隐睾犬睾丸中睾丸激素合成受损的分子背景尚不清楚。在这项研究中,我们分析了参与睾丸类固醇生成四种基因(表达CYP17A1CYP19A1HSD3B2HSD17B3)在未降和对侧从腹股沟单方面隐睾狗阴囊睾丸(Ñ  = 13)和从正常的男性的阴囊生殖腺(Ñ  = 15)。我们发现CYP17A1的转录水平腹股沟性腺中的CYP19A1水平显着升高,而CYP19A1水平降低。对于这两个基因,我们分析了位于睾丸转录因子(NUR77,CREB,CAR和HSF2)的假定靶位点内的启动子区域中单个CpG位点的甲基化水平。观察到CYP17A1启动子中甲基化的减少与其在未下降的性腺中的转录水平增加之间的相关性,但蛋白质水平的变化并不显着。我们还对这两个基因的5′-侧翼区域进行了重新测序,发现了两个已知的多态性位点,CYP17A1中的SNP和CYP19A1中的插入/缺失。但是,变体在受影响(n  = 80)和对照(n  = 75)狗与隐睾症无关。我们初步得出结论,CYP17A1CYP19A1睾丸中的表达改变可能是由于它们暴露于体内温度升高引起的。此外,我们表明,所鉴定的多态性不能被视为与隐睾症易感性相关的标志物。
更新日期:2020-09-12
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