Semen Proteomics of COVID-19 Convalescent Men Reveals Disruption of Key Biological Pathways Relevant to Male Reproductive Function

A considerable section
of males suffered from COVID-19, with many
experiencing long-term repercussions. Recovered males have been documented
to have compromised fertility, albeit the mechanisms remain unclear.
We investigated the impact of COVID-19 on semen proteome following
complete clinical recovery using mass spectrometry. A label-free quantitative
proteomics study involved 10 healthy fertile subjects and 17 COVID-19-recovered
men. With 1% false discovery rate and >1 unique peptide stringency,
MaxQuant analysis found 1099 proteins and 8503 peptides. Of the 48
differentially expressed proteins between the healthy and COVID-19-recovered
groups, 21 proteins were downregulated and 27 were upregulated in
COVID-19-recovered males. The major pathways involved in reproductive
functions, such as sperm–oocyte recognition, testosterone response,
cell motility regulation, adhesion regulation, extracellular matrix
adhesion, and endopeptidase activity, were downregulated in COVID-19-recovered
patients according to bioinformatics analysis. Furthermore, the targeted
approach revealed significant downregulation of semenogelin 1 and
prosaposin, two proteins related to male fertility. Therefore, we
demonstrate the alteration of semen proteome in response to COVID-19,
thus disrupting the male reproductive function despite the patient’s
clinical remission. Hence, to understand fertility-related biological
processes triggered by this infection, a protracted evaluation of
the consequences of COVID-19 in recovered men is warranted.