DCAF13 is essential for mouse uterine function and fertility
Abstract The incidence of female infertility is a growing worldwide concern and a leading cause of population decline. Therefore, understanding the pathogenesis of infertility is of utmost importance. DDB1 and CUL4 Associated Factor 13 (DCAF13) is a significant component of the CRL4 E3 ubiquitin lig...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-08-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-025-02583-w |
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| author | Qianhui Zhou Xiaohui Li Ningjing Wang Liang Zhang Enhui Jiang Kaixuan Wang Xingyu Yan Cong Zhang |
| author_facet | Qianhui Zhou Xiaohui Li Ningjing Wang Liang Zhang Enhui Jiang Kaixuan Wang Xingyu Yan Cong Zhang |
| author_sort | Qianhui Zhou |
| collection | DOAJ |
| description | Abstract The incidence of female infertility is a growing worldwide concern and a leading cause of population decline. Therefore, understanding the pathogenesis of infertility is of utmost importance. DDB1 and CUL4 Associated Factor 13 (DCAF13) is a significant component of the CRL4 E3 ubiquitin ligase complex responsible for recognizing substrates and degrading them after polyubiquitylation. DCAF13 has been implicated in oocyte and embryo development, but its role in the uterus remains elusive. To investigate its function, we generated Dcaf13 conditional knockout (cKO) mice and discovered that the uteri of cKO mice became smaller and thinner as they mature, and the embryos were unable to implant, leading to infertility. Mechanistically, we detected aberrant expression of estrogen and progesterone receptors, along with dysregulation of estrogen- and progesterone-responsive genes in the endometrium. This led to insufficient proliferation of endometrial cells in mice. RNAseq analysis revealed an overall increase in transcription of methylation-related genes, including SUV39H2, leading to higher H3K9me3 levels and consequently hindered cell proliferation in the uterus. Furthermore, DCAF13 knockdown resulted in elevated intracellular H3K9me3 levels. In conclusion, these findings suggest that DCAF13 is essential for maintaining the structure of the uterus and fertility. This study potentially contributes to the development of new strategies aimed at improving female reproductive health. |
| format | Article |
| id | doaj-art-21d4e85569824896bccaa8651316c718 |
| institution | Kabale University |
| issn | 2058-7716 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj-art-21d4e85569824896bccaa8651316c7182025-08-20T03:45:45ZengNature Publishing GroupCell Death Discovery2058-77162025-08-0111111310.1038/s41420-025-02583-wDCAF13 is essential for mouse uterine function and fertilityQianhui Zhou0Xiaohui Li1Ningjing Wang2Liang Zhang3Enhui Jiang4Kaixuan Wang5Xingyu Yan6Cong Zhang7Department of Reproductive Medicine, Ren Ji Hospital, Shanghai Jiao Tong University School of MedicineShandong Provincial Key Laboratory of Animal Resistance Biology, College of Life Sciences, Shandong Normal UniversityShandong Provincial Key Laboratory of Animal Resistance Biology, College of Life Sciences, Shandong Normal UniversityResearch Center of Translational Medicine, Jinan Central Hospital Affiliated to Shandong First Medical UniversityShandong Provincial Key Laboratory of Animal Resistance Biology, College of Life Sciences, Shandong Normal UniversityShandong Provincial Key Laboratory of Animal Resistance Biology, College of Life Sciences, Shandong Normal UniversityDepartment of Reproductive Medicine, Ren Ji Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Reproductive Medicine, Ren Ji Hospital, Shanghai Jiao Tong University School of MedicineAbstract The incidence of female infertility is a growing worldwide concern and a leading cause of population decline. Therefore, understanding the pathogenesis of infertility is of utmost importance. DDB1 and CUL4 Associated Factor 13 (DCAF13) is a significant component of the CRL4 E3 ubiquitin ligase complex responsible for recognizing substrates and degrading them after polyubiquitylation. DCAF13 has been implicated in oocyte and embryo development, but its role in the uterus remains elusive. To investigate its function, we generated Dcaf13 conditional knockout (cKO) mice and discovered that the uteri of cKO mice became smaller and thinner as they mature, and the embryos were unable to implant, leading to infertility. Mechanistically, we detected aberrant expression of estrogen and progesterone receptors, along with dysregulation of estrogen- and progesterone-responsive genes in the endometrium. This led to insufficient proliferation of endometrial cells in mice. RNAseq analysis revealed an overall increase in transcription of methylation-related genes, including SUV39H2, leading to higher H3K9me3 levels and consequently hindered cell proliferation in the uterus. Furthermore, DCAF13 knockdown resulted in elevated intracellular H3K9me3 levels. In conclusion, these findings suggest that DCAF13 is essential for maintaining the structure of the uterus and fertility. This study potentially contributes to the development of new strategies aimed at improving female reproductive health.https://doi.org/10.1038/s41420-025-02583-w |
| spellingShingle | Qianhui Zhou Xiaohui Li Ningjing Wang Liang Zhang Enhui Jiang Kaixuan Wang Xingyu Yan Cong Zhang DCAF13 is essential for mouse uterine function and fertility Cell Death Discovery |
| title | DCAF13 is essential for mouse uterine function and fertility |
| title_full | DCAF13 is essential for mouse uterine function and fertility |
| title_fullStr | DCAF13 is essential for mouse uterine function and fertility |
| title_full_unstemmed | DCAF13 is essential for mouse uterine function and fertility |
| title_short | DCAF13 is essential for mouse uterine function and fertility |
| title_sort | dcaf13 is essential for mouse uterine function and fertility |
| url | https://doi.org/10.1038/s41420-025-02583-w |
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