COVID-19-associated inhibition of energy accumulation pathways in human semen samples

Abstract

Objective: To investigate transcriptional alterations in human semen samples associated with COVID-19 infection.

Design: Retrospective observational cohort study.

Setting: City hospital.

Patients: Ten patients who had recovered from mild COVID-19 infection. Eight of these patients had different sperm abnormalities that were diagnosed before infection. The control group consisted of 5 healthy donors without known abnormalities and no history of COVID-19 infection.

Interventions: We used RNA sequencing to determine gene expression profiles in all studied biosamples. Original standard bioinformatic instruments were used to analyze activation of intracellular molecular pathways.

Main outcome measures: Routine semen analysis, gene expression levels, and molecular pathway activation levels in semen samples.

Results: We found statistically significant inhibition of genes associated with energy production pathways in the mitochondria, including genes involved in the electron transfer chain and genes involved in toll-like receptor signaling. All protein-coding genes encoded by the mitochondrial genome were significantly down-regulated in semen samples collected from patients after recovery from COVID-19.

Conclusions: Our results may provide a molecular basis for the previously observed phenomenon of decreased sperm motility associated with COVID-19 infection. Moreover, the data will be beneficial for the optimization of preconception care for men who have recently recovered from COVID-19 infection.

Keywords: COVID-19; RNA sequencing; gene expression analysis; molecular pathways; sperm.