Investigation of the lncRNA <i>THOR</i> in Mice Highlights the Importance of Noncoding RNAs in Mammalian Male Reproduction
<i>THOR</i> is a highly conserved testis-specific long noncoding RNA (lncRNA). The interaction between <i>THOR</i> and the development of the male reproductive system remains unclear. Herein, CRISPR/Cas9 technology was used to establish a stable <i>THOR</i>-defici...
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MDPI AG
2021-07-01
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| author | Lin Zhou Jianing Li Jinsong Liu Anbei Wang Ying Liu Hao Yu Hongsheng Ouyang Daxin Pang |
| author_facet | Lin Zhou Jianing Li Jinsong Liu Anbei Wang Ying Liu Hao Yu Hongsheng Ouyang Daxin Pang |
| author_sort | Lin Zhou |
| collection | DOAJ |
| description | <i>THOR</i> is a highly conserved testis-specific long noncoding RNA (lncRNA). The interaction between <i>THOR</i> and the development of the male reproductive system remains unclear. Herein, CRISPR/Cas9 technology was used to establish a stable <i>THOR</i>-deficient mouse model, and the relationship between <i>THOR</i> and the fertility of adult male mice was investigated. The male mice in which <i>THOR</i> was deleted were smaller than the WT male mice. Moreover, their survival rate was reduced by 60%, their fertility was reduced by 50%, their testicular size and sperm motility were reduced by 50%, their testicular cell apoptosis was increased by 7-fold, and their ratio of female-to-male offspring was imbalanced (approximately 1:3). Furthermore, to elucidate the mechanisms of male reproductive system development, the mRNA levels of <i>THOR</i> targets were measured by qRT-PCR. Compared with WT mice, the <i>THOR</i>-deficient mice exhibited significantly decreased mRNA levels of IGF2BP1, c-MYC, IGF1, and IGF2. MEK-ERK signaling pathway expression was downregulated as determined by Western blot. We found that <i>THOR</i> targeted the MER-ERK signaling pathway downstream of IGF2 by binding to IGF2BP1 and affected testicular and sperm development in male mice. These results may also provide perspectives for exploring the roles of lncRNAs in human reproductive development and the pathogenesis and potential therapeutic targets of infertility. |
| first_indexed | 2024-03-10T08:59:21Z |
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| language | English |
| last_indexed | 2024-03-10T08:59:21Z |
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| spelling | doaj.art-506b018bdb794157a9caa464447794362023-11-22T06:51:08ZengMDPI AGBiomedicines2227-90592021-07-019885910.3390/biomedicines9080859Investigation of the lncRNA <i>THOR</i> in Mice Highlights the Importance of Noncoding RNAs in Mammalian Male ReproductionLin Zhou0Jianing Li1Jinsong Liu2Anbei Wang3Ying Liu4Hao Yu5Hongsheng Ouyang6Daxin Pang7Key Lab for Zoonoses Research, Ministry of Education, College of Animal Sciences, Jilin University, Changchun 130062, ChinaKey Lab for Zoonoses Research, Ministry of Education, College of Animal Sciences, Jilin University, Changchun 130062, ChinaKey Lab for Zoonoses Research, Ministry of Education, College of Animal Sciences, Jilin University, Changchun 130062, ChinaKey Lab for Zoonoses Research, Ministry of Education, College of Animal Sciences, Jilin University, Changchun 130062, ChinaKey Lab for Zoonoses Research, Ministry of Education, College of Animal Sciences, Jilin University, Changchun 130062, ChinaKey Lab for Zoonoses Research, Ministry of Education, College of Animal Sciences, Jilin University, Changchun 130062, ChinaKey Lab for Zoonoses Research, Ministry of Education, College of Animal Sciences, Jilin University, Changchun 130062, ChinaKey Lab for Zoonoses Research, Ministry of Education, College of Animal Sciences, Jilin University, Changchun 130062, China<i>THOR</i> is a highly conserved testis-specific long noncoding RNA (lncRNA). The interaction between <i>THOR</i> and the development of the male reproductive system remains unclear. Herein, CRISPR/Cas9 technology was used to establish a stable <i>THOR</i>-deficient mouse model, and the relationship between <i>THOR</i> and the fertility of adult male mice was investigated. The male mice in which <i>THOR</i> was deleted were smaller than the WT male mice. Moreover, their survival rate was reduced by 60%, their fertility was reduced by 50%, their testicular size and sperm motility were reduced by 50%, their testicular cell apoptosis was increased by 7-fold, and their ratio of female-to-male offspring was imbalanced (approximately 1:3). Furthermore, to elucidate the mechanisms of male reproductive system development, the mRNA levels of <i>THOR</i> targets were measured by qRT-PCR. Compared with WT mice, the <i>THOR</i>-deficient mice exhibited significantly decreased mRNA levels of IGF2BP1, c-MYC, IGF1, and IGF2. MEK-ERK signaling pathway expression was downregulated as determined by Western blot. We found that <i>THOR</i> targeted the MER-ERK signaling pathway downstream of IGF2 by binding to IGF2BP1 and affected testicular and sperm development in male mice. These results may also provide perspectives for exploring the roles of lncRNAs in human reproductive development and the pathogenesis and potential therapeutic targets of infertility.https://www.mdpi.com/2227-9059/9/8/859<i>THOR</i>testisspermMEK-ERKmice |
| spellingShingle | Lin Zhou Jianing Li Jinsong Liu Anbei Wang Ying Liu Hao Yu Hongsheng Ouyang Daxin Pang Investigation of the lncRNA <i>THOR</i> in Mice Highlights the Importance of Noncoding RNAs in Mammalian Male Reproduction Biomedicines <i>THOR</i> testis sperm MEK-ERK mice |
| title | Investigation of the lncRNA <i>THOR</i> in Mice Highlights the Importance of Noncoding RNAs in Mammalian Male Reproduction |
| title_full | Investigation of the lncRNA <i>THOR</i> in Mice Highlights the Importance of Noncoding RNAs in Mammalian Male Reproduction |
| title_fullStr | Investigation of the lncRNA <i>THOR</i> in Mice Highlights the Importance of Noncoding RNAs in Mammalian Male Reproduction |
| title_full_unstemmed | Investigation of the lncRNA <i>THOR</i> in Mice Highlights the Importance of Noncoding RNAs in Mammalian Male Reproduction |
| title_short | Investigation of the lncRNA <i>THOR</i> in Mice Highlights the Importance of Noncoding RNAs in Mammalian Male Reproduction |
| title_sort | investigation of the lncrna i thor i in mice highlights the importance of noncoding rnas in mammalian male reproduction |
| topic | <i>THOR</i> testis sperm MEK-ERK mice |
| url | https://www.mdpi.com/2227-9059/9/8/859 |
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