NAD+-dependent Sirt6 is a key regulator involved in telomere shortening of in vitro-cultured preimplantation embryos

作者：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 · 发表于：Communications Biology · 年份：2025 · DOI：10.1038/s42003-025-08567-x · 被引用次数：7 · 研究领域：Telomeres, Telomerase, and Senescence、CRISPR and Genetic Engineering、Pluripotent Stem Cells Research

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. NAD+ deficiency impairing Sirt6 function reveals the mechanism of in vitro culture-induced telomere shortening in preimplantation embryos, providing a target to improve IVF outcomes.