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CRISRP/Cas9-mediated knockout of Mct8 reveals a functional involvement of Mct8 in testis and sperm development in a rat

Cited 9 time in Web of Science Cited 7 time in Scopus
Authors

Bae, Hee Sook; Jin, Yun-Kyeong; Ham, Sangwoo; Kim, Hee Kyoung; Shin, Hyejung; Cho, Gyu-bon; Lee, Kyu Jun; Lee, Hohyeon; Kim, Kyeong-Min; Koo, Ok-Jae; Jang, Goo; Lee, Jung Min; Lee, Jae Young

Issue Date
2020-07-07
Publisher
Nature Publishing Group
Citation
Scientific Reports, Vol.10 No.1, p. 11148
Abstract
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.
ISSN
2045-2322
URI
https://hdl.handle.net/10371/195032
DOI
https://doi.org/10.1038/s41598-020-67594-2
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