<i>HDAC1</i>-Mediated lncRNA Stimulatory Factor of Follicular Development to Inhibit the Apoptosis of Granulosa Cells and Regulate Sexual Maturity through miR-202-3p-<i>COX1</i> Axis
Abnormal sexual maturity exhibits significant detrimental effects on adult health outcomes, and previous studies have indicated that targeting histone acetylation might serve as a potential therapeutic approach to regulate sexual maturity. However, the mechanisms that account for it remain to be fur...
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MDPI AG
2023-11-01
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| author | Xiaofeng Zhou Yingting He Hongyan Quan Xiangchun Pan Yinqi Zhou Zhe Zhang Xiaolong Yuan Jiaqi Li |
| author_facet | Xiaofeng Zhou Yingting He Hongyan Quan Xiangchun Pan Yinqi Zhou Zhe Zhang Xiaolong Yuan Jiaqi Li |
| author_sort | Xiaofeng Zhou |
| collection | DOAJ |
| description | Abnormal sexual maturity exhibits significant detrimental effects on adult health outcomes, and previous studies have indicated that targeting histone acetylation might serve as a potential therapeutic approach to regulate sexual maturity. However, the mechanisms that account for it remain to be further elucidated. Using the mouse model, we showed that Trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor, downregulated the protein level of Hdac1 in ovaries to promote the apoptosis of granulosa cells (GCs), and thus arrested follicular development and delayed sexual maturity. Using porcine GCs as a cell model, a novel sexual maturity-associated lncRNA, which was named as the stimulatory factor of follicular development (<i>SFFD</i>), transcribed from mitochondrion and mediated by <i>HDAC1</i>, was identified using RNA sequencing. Mechanistically, <i>HDAC1</i> knockdown significantly reduced the H3K27ac level at the −953/−661 region of <i>SFFD</i> to epigenetically inhibit its transcription. <i>SFFD</i> knockdown released miR-202-3p to reduce the expression of cyclooxygenase 1 (<i>COX1</i>), an essential rate-limited enzyme involved in prostaglandin synthesis. This reduction inhibited the proliferation and secretion of 17β-estradiol (E2) while promoting the apoptosis of GCs. Consequently, follicular development was arrested and sexual maturity was delayed. Taken together, <i>HDAC1</i> knockdown-mediated <i>SFFD</i> downregulation promoted the apoptosis of GCs through the miR-202-3p-<i>COX1</i> axis and lead to delayed sexual maturity. Our findings reveal a novel regulatory network modulated by <i>HDAC1</i>, and <i>HDAC1</i>-mediated <i>SFFD</i> may be a promising new therapeutic target to treat delayed sexual maturity. |
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| spelling | doaj.art-c7da82e6bde849b18712320b6ac9349f2023-12-08T15:13:12ZengMDPI AGCells2073-44092023-11-011223273410.3390/cells12232734<i>HDAC1</i>-Mediated lncRNA Stimulatory Factor of Follicular Development to Inhibit the Apoptosis of Granulosa Cells and Regulate Sexual Maturity through miR-202-3p-<i>COX1</i> AxisXiaofeng Zhou0Yingting He1Hongyan Quan2Xiangchun Pan3Yinqi Zhou4Zhe Zhang5Xiaolong Yuan6Jiaqi Li7Guangdong Laboratory of Lingnan Modern Agriculture, National Engineering Research Center for Breeding Swine Industry, State Key Laboratory of Swine and Poultry Breeding Industry, Guangdong Provincial Key Laboratory of Agro-Animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou 510642, ChinaGuangdong Laboratory of Lingnan Modern Agriculture, National Engineering Research Center for Breeding Swine Industry, State Key Laboratory of Swine and Poultry Breeding Industry, Guangdong Provincial Key Laboratory of Agro-Animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou 510642, ChinaGuangdong Laboratory of Lingnan Modern Agriculture, National Engineering Research Center for Breeding Swine Industry, State Key Laboratory of Swine and Poultry Breeding Industry, Guangdong Provincial Key Laboratory of Agro-Animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou 510642, ChinaGuangdong Laboratory of Lingnan Modern Agriculture, National Engineering Research Center for Breeding Swine Industry, State Key Laboratory of Swine and Poultry Breeding Industry, Guangdong Provincial Key Laboratory of Agro-Animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou 510642, ChinaGuangdong Laboratory of Lingnan Modern Agriculture, National Engineering Research Center for Breeding Swine Industry, State Key Laboratory of Swine and Poultry Breeding Industry, Guangdong Provincial Key Laboratory of Agro-Animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou 510642, ChinaGuangdong Laboratory of Lingnan Modern Agriculture, National Engineering Research Center for Breeding Swine Industry, State Key Laboratory of Swine and Poultry Breeding Industry, Guangdong Provincial Key Laboratory of Agro-Animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou 510642, ChinaGuangdong Laboratory of Lingnan Modern Agriculture, National Engineering Research Center for Breeding Swine Industry, State Key Laboratory of Swine and Poultry Breeding Industry, Guangdong Provincial Key Laboratory of Agro-Animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou 510642, ChinaGuangdong Laboratory of Lingnan Modern Agriculture, National Engineering Research Center for Breeding Swine Industry, State Key Laboratory of Swine and Poultry Breeding Industry, Guangdong Provincial Key Laboratory of Agro-Animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou 510642, ChinaAbnormal sexual maturity exhibits significant detrimental effects on adult health outcomes, and previous studies have indicated that targeting histone acetylation might serve as a potential therapeutic approach to regulate sexual maturity. However, the mechanisms that account for it remain to be further elucidated. Using the mouse model, we showed that Trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor, downregulated the protein level of Hdac1 in ovaries to promote the apoptosis of granulosa cells (GCs), and thus arrested follicular development and delayed sexual maturity. Using porcine GCs as a cell model, a novel sexual maturity-associated lncRNA, which was named as the stimulatory factor of follicular development (<i>SFFD</i>), transcribed from mitochondrion and mediated by <i>HDAC1</i>, was identified using RNA sequencing. Mechanistically, <i>HDAC1</i> knockdown significantly reduced the H3K27ac level at the −953/−661 region of <i>SFFD</i> to epigenetically inhibit its transcription. <i>SFFD</i> knockdown released miR-202-3p to reduce the expression of cyclooxygenase 1 (<i>COX1</i>), an essential rate-limited enzyme involved in prostaglandin synthesis. This reduction inhibited the proliferation and secretion of 17β-estradiol (E2) while promoting the apoptosis of GCs. Consequently, follicular development was arrested and sexual maturity was delayed. Taken together, <i>HDAC1</i> knockdown-mediated <i>SFFD</i> downregulation promoted the apoptosis of GCs through the miR-202-3p-<i>COX1</i> axis and lead to delayed sexual maturity. Our findings reveal a novel regulatory network modulated by <i>HDAC1</i>, and <i>HDAC1</i>-mediated <i>SFFD</i> may be a promising new therapeutic target to treat delayed sexual maturity.https://www.mdpi.com/2073-4409/12/23/2734sexual maturityfollicular developmentgranulosa cellshistone acetylationlncRNAs |
| spellingShingle | Xiaofeng Zhou Yingting He Hongyan Quan Xiangchun Pan Yinqi Zhou Zhe Zhang Xiaolong Yuan Jiaqi Li <i>HDAC1</i>-Mediated lncRNA Stimulatory Factor of Follicular Development to Inhibit the Apoptosis of Granulosa Cells and Regulate Sexual Maturity through miR-202-3p-<i>COX1</i> Axis Cells sexual maturity follicular development granulosa cells histone acetylation lncRNAs |
| title | <i>HDAC1</i>-Mediated lncRNA Stimulatory Factor of Follicular Development to Inhibit the Apoptosis of Granulosa Cells and Regulate Sexual Maturity through miR-202-3p-<i>COX1</i> Axis |
| title_full | <i>HDAC1</i>-Mediated lncRNA Stimulatory Factor of Follicular Development to Inhibit the Apoptosis of Granulosa Cells and Regulate Sexual Maturity through miR-202-3p-<i>COX1</i> Axis |
| title_fullStr | <i>HDAC1</i>-Mediated lncRNA Stimulatory Factor of Follicular Development to Inhibit the Apoptosis of Granulosa Cells and Regulate Sexual Maturity through miR-202-3p-<i>COX1</i> Axis |
| title_full_unstemmed | <i>HDAC1</i>-Mediated lncRNA Stimulatory Factor of Follicular Development to Inhibit the Apoptosis of Granulosa Cells and Regulate Sexual Maturity through miR-202-3p-<i>COX1</i> Axis |
| title_short | <i>HDAC1</i>-Mediated lncRNA Stimulatory Factor of Follicular Development to Inhibit the Apoptosis of Granulosa Cells and Regulate Sexual Maturity through miR-202-3p-<i>COX1</i> Axis |
| title_sort | i hdac1 i mediated lncrna stimulatory factor of follicular development to inhibit the apoptosis of granulosa cells and regulate sexual maturity through mir 202 3p i cox1 i axis |
| topic | sexual maturity follicular development granulosa cells histone acetylation lncRNAs |
| url | https://www.mdpi.com/2073-4409/12/23/2734 |
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