Transmission of reduced levels of miR-34/449 from sperm to preimplantation embryos is a key step in the transgenerational epigenetic inheritance of the effects of paternal chronic social instability stress.
Level 5 - mechanism / opinion, no new human data
Preclinical animal model and in vitro cell culture mechanistic research.
PubMed 38739481 · doi:10.1080/15592294.2024.2346694
What was done
Researchers studied how paternal chronic social instability (CSI) stress in mice transmits behavioral traits across generations via sperm microRNAs. They microinjected/restored miR-34c into preimplantation embryos (PIEs) derived from CSI-stressed male mice and evaluated anxiety and sociability in adult female offspring, as well as sperm miR-34/449 levels in adult male offspring. They also examined whether miR-34c induces expression of its own gene and miR-449 in mouse PIEs and human embryonic stem cells.
What was found
Restoring miR-34c in PIEs derived from CSI-stressed males prevented elevated anxiety and social deficits normally observed in adult female offspring, and partially restored sperm miR-34/449 levels in male offspring. Inducing miR-34c in PIEs stimulated endogenous expression of its own gene and miR-449, demonstrating an amplification mechanism that explains how sperm containing approximately 50-fold lower miRNA levels than PIEs can trigger downstream embryonic effects. Similar auto-induction of miR-34/449 by miR-34c was observed in human embryonic stem cells. The abstract does not provide exact sample sizes or numerical behavioral and molecular effect sizes.
Why it matters
This identifies an embryonic positive-feedback mechanism for sperm-transmitted miRNAs, explaining how trace paternal non-coding RNAs can alter development and transmit stress phenotypes across generations.
Limits
Findings rely on mouse models and in vitro human stem cell assays, so direct clinical transmission in humans is not proven. The abstract reports no numerical values, confidence intervals, or sample sizes.
Cited by
- supports Epigenetic transmission of stress and learning markers can span multiple generations in rodents and humans.