Paternal Circadian Disruption Impairs Offspring Cognition via Sperm microRNAs
Kexin Zou1, Sisi Luo1,2, Binliang Tang3
1Institute of Reproduction and Development, Shanghai Key Laboratory of Reproduction and Development, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China.
Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|April 28, 2026
Summary
Paternal circadian disruption impairs male offspring memory and neural function. Sperm microRNAs (miRNAs) mediate this intergenerational effect, highlighting epigenetic inheritance of neurobehavioral deficits.
Area of Science:
- Neuroscience
- Epigenetics
- Reproductive Biology
Background:
- Paternal lifestyle factors influence offspring health.
- The impact of paternal circadian rhythm disruption on offspring neural development and cognition remains unclear.
Purpose of the Study:
- To investigate the effects of paternal circadian disruption on offspring neural development and cognitive function.
- To explore the role of sperm-borne small RNAs, particularly microRNAs (miRNAs), in mediating these intergenerational effects.
Main Methods:
- Male mice were exposed to constant light (LL-F0) to disrupt circadian rhythms.
- Offspring (F1) cognitive function and hippocampal synaptic plasticity were assessed.
- Small RNA sequencing of sperm was performed, and specific miRNAs were quantified in human sperm.
- Microinjection of sperm small RNAs or synthetic miRNAs into zygotes was conducted to assess causality.
Main Results:
- Paternal circadian disruption led to memory dysfunction and impaired hippocampal synaptic plasticity in male, but not female, offspring.
- Altered small RNA profiles, including specific miRNAs, were observed in the sperm of disrupted fathers.
- Upregulation of miR-92a-3p was validated in human sperm.
- Microinjection of LL-F0 sperm small RNAs or specific miRNAs replicated cognitive deficits in offspring, while inhibition partially reversed them.
Conclusions:
- Paternal circadian disruption can negatively impact male offspring's neural development and cognitive function.
- Sperm-borne miRNAs are implicated in the intergenerational transmission of neurobehavioral deficits.
- Epigenetic modifications in germ cells may underlie the inheritance of environmentally induced traits.
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