Xavier · Human reproduction update 2019 · systematic review of mechanistic studies · n=?

Transgenerational inheritance: how impacts to the epigenetic and genetic information of parents affect offspring health.

Cited 255 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Systematic review of basic biology, animal models, and mechanistic pathways of transgenerational inheritance.

PubMed 31374565 · doi:10.1093/humupd/dmz017 · record verified 2026-08-29

What was done

The authors systematically searched PubMed using keywords covering transgenerational inheritance, epigenetic modifications, paternal and maternal inheritable traits, and environmental/biological factors. The review focused on mammalian systems (excluding plant models) to evaluate how environmental exposures, aging, diet, and toxicants alter germline DNA methylation, histone modifications, and non-coding RNAs, and how these modifications survive developmental epigenetic reprogramming to influence descendant phenotypes.

What was found

The abstract reports no quantitative metrics or effect sizes. Qualitatively, the review identified evidence in rodents and humans demonstrating that specific genomic domains and histone modification sites resist genome-wide demethylation and reprogramming events. These persistent modifications at enhancer and promoter regions, combined with spontaneous germline genetic mutations, transmit phenotypic changes across generations, contributing to conditions such as dominant genetic disorders, autism, and spontaneous schizophrenia.

Why it matters

This review synthesizes the biological mechanisms by which parental environmental exposures alter the germline epigenome, demonstrating that non-DNA sequence modifications can escape developmental erasure and directly impact offspring disease susceptibility.

Limits

The abstract provides no quantitative data, sample sizes, or number of included studies. The underlying evidence relies heavily on rodent models, which may not directly translate to human reproductive biology and germline reprogramming dynamics.

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