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 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 epige

SUBMITTER: Li D 

PROVIDER: S-EPMC12375090 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature