Advanced science (Weinheim, Baden-Wurttemberg, Germany)Apr 28, 2026

Disrupting Fathers' Body Clocks May Affect Offspring Thinking Through Changes in Sperm microRNAs

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jun 28, 2026

Abstract

Essence

In mice, paternal circadian disruption before conception impaired male offspring cognition, and sperm microRNAs appear to carry part of that effect.

Evidence

This preclinical mouse study exposed fathers to constant light, found memory and hippocampal plasticity deficits in male but not female F1 offspring, and used sperm small-RNA microinjection plus zygote miRNA inhibition to partly reproduce and reverse the phenotype.

Caveat

The main evidence is from mice and the reversal was only partial, so the mechanism's completeness and relevance to humans remain uncertain.

Simplified

A father's lifestyle can impact offspring's health. However, it is unclear whether and how paternal circadian rhythm disruption affects offspring neural development and cognitive function. Here, we show that male mice exposed to constant light (LL-F0) led to memory dysfunction and impaired hippocampal synaptic plasticity in male, but not female, F1 offspring (LL-F1). Paternal circadian disruption altered expression profiles of small RNAs, especially microRNAs (miRNAs), in mouse sperm. These miRNA changes were associated with chromatin accessible regions in spermatogonial stem cells, pointing to an early germline origin of the disrupted epigenetic state. In human sperm, we identified and validated upregulation of miR-92a-3p. Microinjection of total small RNAs from LL-F0 sperm or synthetic miR-92a-3p/miR-25-3p into zygotes was sufficient to phenocopy offspring cognitive impairment, whereas inhibition of these miRNAs in zygotes partially reversed the phenotype. These findings support a role for sperm-borne miRNAs in the intergenerational transmission of neurobehavioral deficits induced by paternal circadian disruption.