NAD+-dependent Sirt6 is a key regulator involved in telomere shortening of in vitro-cultured preimplantation embryos
Abstract Telomere length (TL) is important for maintaining the individual health of a species. Recent studies shows that in vitro fertilization therapy can drastically reduce TL in offspring, however, the underlying molecular mechanism remains unknown. Sirt6 is a NAD+-dependent epigenetic regulator...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-08-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-08567-x |
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| author | Danjun Li Wenzhi Li Xiaoyu Liao Shutian Jiang Meng Ma Zhijie Hu Kaibo Lin Weina Yu Xue Sun Yong Fan Haibo Wu Mingru Yin Li Wang Lun Suo Hui Long Xuefeng Lu Yanping Kuang Qifeng Lyu |
| author_facet | Danjun Li Wenzhi Li Xiaoyu Liao Shutian Jiang Meng Ma Zhijie Hu Kaibo Lin Weina Yu Xue Sun Yong Fan Haibo Wu Mingru Yin Li Wang Lun Suo Hui Long Xuefeng Lu Yanping Kuang Qifeng Lyu |
| author_sort | Danjun Li |
| collection | DOAJ |
| description | Abstract Telomere length (TL) is important for maintaining the individual health of a species. Recent studies shows that in vitro fertilization therapy can drastically reduce TL in offspring, however, the underlying molecular mechanism remains unknown. Sirt6 is a NAD+-dependent epigenetic regulator that has recently been found to play an important role in maintaining telomere stability. Here, we report that NAD+ deficiency in in vitro-cultured blastocysts impairs Sirt6 function, triggering telomere shortening of the inner cell mass and possibly affecting newborns. This phenotype could be effectively mitigated by supplementation with nicotinamide mononucleotide (NAD+ precursor) during in vitro culture, while it could not be achieved in Sirt6 conditional knockout embryos. mtROS accumulation and epigenetic modifications may also be involved in this process. Our results reveal the mechanism by which in vitro culture induces telomere shortening in preimplantation embryos, providing a potential target for improving in vitro culture conditions. |
| format | Article |
| id | doaj-art-ce0f5706da244d97b20d41c1721623ed |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-ce0f5706da244d97b20d41c1721623ed2025-08-24T11:45:46ZengNature PortfolioCommunications Biology2399-36422025-08-018111510.1038/s42003-025-08567-xNAD+-dependent Sirt6 is a key regulator involved in telomere shortening of in vitro-cultured preimplantation embryosDanjun Li0Wenzhi Li1Xiaoyu Liao2Shutian Jiang3Meng Ma4Zhijie Hu5Kaibo Lin6Weina Yu7Xue Sun8Yong Fan9Haibo Wu10Mingru Yin11Li Wang12Lun Suo13Hui Long14Xuefeng Lu15Yanping Kuang16Qifeng Lyu17Department of Assisted Reproduction, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Assisted Reproduction, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Assisted Reproduction, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Assisted Reproduction, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Assisted Reproduction, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Assisted Reproduction, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Assisted Reproduction, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Assisted Reproduction, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Assisted Reproduction, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Assisted Reproduction, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Assisted Reproduction, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Assisted Reproduction, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Assisted Reproduction, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Assisted Reproduction, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Assisted Reproduction, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Assisted Reproduction, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Assisted Reproduction, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Assisted Reproduction, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineAbstract Telomere length (TL) is important for maintaining the individual health of a species. Recent studies shows that in vitro fertilization therapy can drastically reduce TL in offspring, however, the underlying molecular mechanism remains unknown. Sirt6 is a NAD+-dependent epigenetic regulator that has recently been found to play an important role in maintaining telomere stability. Here, we report that NAD+ deficiency in in vitro-cultured blastocysts impairs Sirt6 function, triggering telomere shortening of the inner cell mass and possibly affecting newborns. This phenotype could be effectively mitigated by supplementation with nicotinamide mononucleotide (NAD+ precursor) during in vitro culture, while it could not be achieved in Sirt6 conditional knockout embryos. mtROS accumulation and epigenetic modifications may also be involved in this process. Our results reveal the mechanism by which in vitro culture induces telomere shortening in preimplantation embryos, providing a potential target for improving in vitro culture conditions.https://doi.org/10.1038/s42003-025-08567-x |
| spellingShingle | Danjun Li Wenzhi Li Xiaoyu Liao Shutian Jiang Meng Ma Zhijie Hu Kaibo Lin Weina Yu Xue Sun Yong Fan Haibo Wu Mingru Yin Li Wang Lun Suo Hui Long Xuefeng Lu Yanping Kuang Qifeng Lyu NAD+-dependent Sirt6 is a key regulator involved in telomere shortening of in vitro-cultured preimplantation embryos Communications Biology |
| title | NAD+-dependent Sirt6 is a key regulator involved in telomere shortening of in vitro-cultured preimplantation embryos |
| title_full | NAD+-dependent Sirt6 is a key regulator involved in telomere shortening of in vitro-cultured preimplantation embryos |
| title_fullStr | NAD+-dependent Sirt6 is a key regulator involved in telomere shortening of in vitro-cultured preimplantation embryos |
| title_full_unstemmed | NAD+-dependent Sirt6 is a key regulator involved in telomere shortening of in vitro-cultured preimplantation embryos |
| title_short | NAD+-dependent Sirt6 is a key regulator involved in telomere shortening of in vitro-cultured preimplantation embryos |
| title_sort | nad dependent sirt6 is a key regulator involved in telomere shortening of in vitro cultured preimplantation embryos |
| url | https://doi.org/10.1038/s42003-025-08567-x |
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