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Embryonic signatures of intergenerational epigenetic inheritance across paternal environments and genetic backgrounds.


ABSTRACT: The paternal preconception environment has been implicated as a modulator of phenotypic traits and disease risk in F1 offspring. However, the prevalence and mechanisms of such intergenerational epigenetic inheritance (IEI) in mammals remain poorly defined. Moreover, the interplay between paternal exposure, genetics, and age on emergent offspring features is unexplored. Here, we measure the quantitative impact of three paternal environments on early embryogenesis across genetic backgrounds. Using in vitro fertilisation (IVF) at scale, we capture batch-robust transcriptomic signatures of IEI with single-blastocyst resolution. Amongst these, paternal gut microbiota dysbiosis is linked with aberrant expression of (extra-)embryonic lineage regulators in blastocysts. In contrast, a paternal low-

SUBMITTER: Dura M 

PROVIDER: S-EPMC12624057 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature