Figure 3.

Potential mechanistic pathways involved in the proposed reprogramming of offspring phenotypes due to paternal SARS-CoV-2 infection and immune activation.

High levels of systemic proinflammatory cytokines, such as TNF-α and IL-6, and neutrophils can potentially damage the testes and affect spermatogenesis. Since many epigenetic changes occur during spermatogenesis, these immune factors may be able to alter the sperm epigenome. Furthermore, stress and metabolic changes that may occur during SARS-CoV-2 infection could also affect specific contents of the sperm, such as noncoding RNAs. The sperm can transmit this epigenetic information to the oocyte at fertilisation, ultimately leading to changes in the expression of genes involved in embryonic development. This could modulate offspring development and function, and possibly alter disease susceptibility. Created with BioRender.com. Abbreviations: IL, interleukin; ROS, reactive oxygen species; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; TNF-α, tumour necrosis factor-α.