tetano
Editor, Senior Moderator
Nat Commun
. 2025 Oct 11;16(1):9045.
doi: 10.1038/s41467-025-64473-0. Paternal SARS-CoV-2 infection impacts sperm small noncoding RNAs and increases anxiety in offspring in a sex-dependent manner
Elizabeth A Kleeman[SUP] 1 2 [/SUP], Carolina Gubert[SUP] #[/SUP][SUP] 3 [/SUP], Sonali N Reisinger[SUP] #[/SUP][SUP] 1 [/SUP], Kathryn C Davidson[SUP] 4 5 [/SUP], Da Lu[SUP] 1 2 [/SUP], Merle Dayton[SUP] 4 [/SUP], Liana Mackiewicz[SUP] 4 [/SUP], Bethany A Masson[SUP] 1 2 [/SUP], Pranav Adithya[SUP] 1 2 [/SUP], Alexandra L Garnham[SUP] 4 5 [/SUP], Gemma Stathatos[SUP] 6 [/SUP], Moira K O'Bryan[SUP] 6 [/SUP], Rikeish R Muralitharan[SUP] 7 8 [/SUP], Francine Z Marques[SUP] 7 8 9 [/SUP], Shanshan Li[SUP] 1 [/SUP], Huan Liao[SUP] 1 [/SUP], Shae McLaughlin[SUP] 1 [/SUP], Emmet T Keough[SUP] 1 [/SUP], Michelle Y Wheeler[SUP] 1 [/SUP], Pamudika Kiridena[SUP] 1 2 [/SUP], Marcel Doerflinger[SUP] 4 5 [/SUP], Marc Pellegrini[SUP] 4 5 [/SUP], Anthony J Hannan[SUP] 10 11 12 [/SUP]
Affiliations
Given that the SARS-CoV-2 virus, and the COVID-19 pandemic, constitutes a major environmental challenge faced by billions of people worldwide, we investigated whether paternal pre-conceptual SARS-CoV-2 infection has impacts on sperm RNA content, and intergenerational (F1) and transgenerational (F2) effects on offspring phenotypes. Using an established mouse-adapted SARS-CoV-2 (P21) preclinical model, we infected adult male mice with the virus, or performed a mock control infection, and bred them with naïve female mice four weeks later, when males were no longer infectious. Here we show that offspring of infected sires display increased anxiety-like behaviors. Additionally, the F1 offspring have significant transcriptomic changes in their hippocampus. Various sperm small noncoding RNAs, including PIWI-interacting RNAs, transfer-derived RNAs and microRNAs, are differentially altered by prior paternal SARS-CoV-2 infection. Microinjection of RNA from the sperm of SARS-CoV-2 infected males into fertilized oocytes leads to a phenotype resembling that of the naturally born F1 offspring, supporting the interpretation that sperm RNAs are contributing to the outcomes of our paternal SARS-CoV-2 model. Therefore, this study provides evidence that paternal SARS-CoV-2 infection impacts sperm and affects offspring phenotypes. These findings have public-health implications and inform further research in males affected by COVID-19, and their offspring.
. 2025 Oct 11;16(1):9045.
doi: 10.1038/s41467-025-64473-0. Paternal SARS-CoV-2 infection impacts sperm small noncoding RNAs and increases anxiety in offspring in a sex-dependent manner
Elizabeth A Kleeman[SUP] 1 2 [/SUP], Carolina Gubert[SUP] #[/SUP][SUP] 3 [/SUP], Sonali N Reisinger[SUP] #[/SUP][SUP] 1 [/SUP], Kathryn C Davidson[SUP] 4 5 [/SUP], Da Lu[SUP] 1 2 [/SUP], Merle Dayton[SUP] 4 [/SUP], Liana Mackiewicz[SUP] 4 [/SUP], Bethany A Masson[SUP] 1 2 [/SUP], Pranav Adithya[SUP] 1 2 [/SUP], Alexandra L Garnham[SUP] 4 5 [/SUP], Gemma Stathatos[SUP] 6 [/SUP], Moira K O'Bryan[SUP] 6 [/SUP], Rikeish R Muralitharan[SUP] 7 8 [/SUP], Francine Z Marques[SUP] 7 8 9 [/SUP], Shanshan Li[SUP] 1 [/SUP], Huan Liao[SUP] 1 [/SUP], Shae McLaughlin[SUP] 1 [/SUP], Emmet T Keough[SUP] 1 [/SUP], Michelle Y Wheeler[SUP] 1 [/SUP], Pamudika Kiridena[SUP] 1 2 [/SUP], Marcel Doerflinger[SUP] 4 5 [/SUP], Marc Pellegrini[SUP] 4 5 [/SUP], Anthony J Hannan[SUP] 10 11 12 [/SUP]
Affiliations
- PMID: 41076487
- PMCID: PMC12515249
- DOI: 10.1038/s41467-025-64473-0
Given that the SARS-CoV-2 virus, and the COVID-19 pandemic, constitutes a major environmental challenge faced by billions of people worldwide, we investigated whether paternal pre-conceptual SARS-CoV-2 infection has impacts on sperm RNA content, and intergenerational (F1) and transgenerational (F2) effects on offspring phenotypes. Using an established mouse-adapted SARS-CoV-2 (P21) preclinical model, we infected adult male mice with the virus, or performed a mock control infection, and bred them with naïve female mice four weeks later, when males were no longer infectious. Here we show that offspring of infected sires display increased anxiety-like behaviors. Additionally, the F1 offspring have significant transcriptomic changes in their hippocampus. Various sperm small noncoding RNAs, including PIWI-interacting RNAs, transfer-derived RNAs and microRNAs, are differentially altered by prior paternal SARS-CoV-2 infection. Microinjection of RNA from the sperm of SARS-CoV-2 infected males into fertilized oocytes leads to a phenotype resembling that of the naturally born F1 offspring, supporting the interpretation that sperm RNAs are contributing to the outcomes of our paternal SARS-CoV-2 model. Therefore, this study provides evidence that paternal SARS-CoV-2 infection impacts sperm and affects offspring phenotypes. These findings have public-health implications and inform further research in males affected by COVID-19, and their offspring.