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CRISRP/Cas9-mediated knockout of Mct8 reveals a functional involvement of Mct8 in testis and sperm development in a rat.
Scientific Reports ( IF 3.8 ) Pub Date : 2020-07-07 , DOI: 10.1038/s41598-020-67594-2
Hee Sook Bae 1 , Yun-Kyeong Jin 2 , Sangwoo Ham 1 , Hee Kyoung Kim 2 , Hyejung Shin 1 , Gyu-Bon Cho 1 , Kyu Jun Lee 1 , Hohyeon Lee 1 , Kyeong-Min Kim 2 , Ok-Jae Koo 1 , Goo Jang 2 , Jung Min Lee 1, 3 , Jae Young Lee 1
Affiliation  

Thyroid hormone (TH) has long been believed to play a minor role in male reproduction. However, evidences from experimental model of thyrotoxicosis or hypothyroidism suggests its role in spermatogenesis. Cellular action of TH requires membrane transport via specific transporters such as monocarboxylate transporter 8 (MCT8). SLC16A2 (encodes for MCT8) inactivating mutation in humans can lead to Allan-Herndon Dudley-syndrome, a X-linked psychomotor and growth retardation. These patients present cryptorchidism which suggests a role of MCT8 during spermatogenesis. In this study, we found that Mct8 is highly expressed during early postnatal development and decreases its expression in the adulthood of testis of wild-type male rats. Histological analysis revealed that spermatogonia largely lacks MCT8 expression while spermatocytes and maturing spermatids highly express MCT8. To further understand the role of Mct8 during spermatogenesis, we generated Slc16a2 (encodes MCT8) knockout rats using CRISPR/Cas9. Serum THs (T3 and T4) level were significantly altered in Slc16a2 knockout rats when compared to wild-type littermates during early to late postnatal development. Unlike Slc16a2 knockout mice, Slc16a2 knockout rats showed growth delay during early to late postnatal development. In adult Slc16a2 knockout rats, we observed reduced sperm motility and viability. Collectively, our data unveil a functional involvement of MCT8 in spermatogenesis, underscoring the importance of TH signaling and action during spermatogenesis.



中文翻译:

CRISRP / Cas9介导的敲除Mct8揭示了Mct8在大鼠睾丸和精子发育中的功能参与。

长期以来,人们一直认为甲状腺激素(TH)在男性生殖中起着次要作用。然而,甲状腺毒症或甲状腺功能减退症实验模型的证据表明其在精子发生中的作用。TH的细胞作用需要通过特定的转运蛋白如单羧酸酯转运蛋白8(MCT8)进行膜转运。SLC16A2(编码MCT8)人体内的失活突变可能导致艾伦-汉登·达德利综合征,X连锁的精神运动和发育迟缓。这些患者表现出隐睾症,表明MCT8在精子发生过程中发挥了作用。在这项研究中,我们发现Mct8在产后早期发育过程中高度表达,并在野生型雄性大鼠睾丸成年期降低其表达。组织学分析显示,精原细胞大量缺乏MCT8表达,而精细胞和成熟精细胞高度表达MCT8。为了进一步了解Mct8在精子发生中的作用,我们使用CRISPR / Cas9生成了Slc16a2(编码MCT8)敲除大鼠。血清THS(T3和T4)在水平分别显著改变SLC16A2与野生型同窝仔相比,在出生后早期到晚期的基因敲除大鼠。与Slc16a2基因敲除小鼠不同,Slc16a2基因敲除大鼠在出生后早期至晚期显示出生长延迟。在成年Slc16a2基因敲除大鼠中,我们观察到精子活力和活力降低。总体而言,我们的数据揭示了MCT8在精子发生中的功能参与,强调了TH信号和精子发生过程中作用的重要性。

更新日期:2020-07-07
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