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. 2025 Mar 21;26(1):281.
doi: 10.1186/s12864-025-11473-5.

Seminal plasma proteomics of asymptomatic COVID-19 patients reveals disruption of male reproductive function

Jialyu Huang #  1 , Yufang Su #  2 , Jiawei Wang #  3 , Zheng Fang  4 , Yiwei Zhang  5 , Hong Chen  1 , Xinxia Wan  1 , Yuanhuan Xiong  2 , Ning Song  6 , Houyang Chen  7 , Xingwu Wu  8
Affiliations

Seminal plasma proteomics of asymptomatic COVID-19 patients reveals disruption of male reproductive function

Jialyu Huang et al. BMC Genomics. .

Abstract

Background: A considerable proportion of males suffer from asymptomatic SARS-CoV-2 infection, while the effect on reproductive function and underlying pathomechanisms remain unclear.

Results: The total sperm count decreased evidently after asymptomatic infection, yet all semen samples were tested to be SARS-CoV-2 RNA negative. Through label‑free quantitative proteomic profiling, a total of 733 proteins were further identified in seminal plasma from 11 COVID-19 patients and seven uninfected controls. Of the 37 differentially expressed proteins, 23 were upregulated and 14 were downregulated in the COVID-19 group compared with control. Functional annotations in Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome showed that these proteins were highly enriched in infection, inflammation, and immunity-related pathways as well as spermatogenesis-associated biological process. Four proteins were significantly correlated with one or more semen parameters in Spearman's coefficient analysis, and seven were filtered as potential hub proteins from the interaction network by MCODE and Cytohubba algorithms. Furthermore, we verified the proteomic results by Western blot analysis of three representative proteins (ITLN1, GSTM2, and PSAP) in the validation cohort.

Conclusions: In summary, our study showed that acute asymptomatic COVID-19 could alter the seminal plasma protein profile without direct testicular infection and consequently lead to impaired semen quality. These novel findings should enlighten the physicians about the adverse effects of SARS-CoV-2 infection on male fertility, and provide valuable resources for reproductive biologists to further decipher the molecular functions.

Keywords: COVID-19; Proteomics; SARS-CoV-2; Seminal plasma.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The study was approved by the Reproductive Medicine Ethics Committee of Jiangxi Maternal and Child Health Hospital, and conducted in accordance with the Declaration of Helsinki. All patients signed informed contents before participation. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Identification of differentially expressed proteins (DEPs) in seminal plasma. (A) Volcano plot of the 34 DEPs between COVID-19 (n = 11) and control (n = 7) groups. (B) Heatmap of the 34 DEPs between COVID-19 (n = 11) and control (n = 7) groups. The criteria for DEPs are a fold change > 1.5 and a P-value < 0.05 from the t-test
Fig. 2
Fig. 2
Functional enrichment analyses of differentially expressed proteins in seminal plasma. (A) Gene Ontology enrichment analysis. (B) Kyoto Encyclopedia of Genes and Genomes enrichment analysis. (C) Reactome enrichment analysis
Fig. 3
Fig. 3
Correlation analyses of differentially expressed proteins (DEPs) and semen parameters. (A) Correlation heatmap among the 34 DEPs. (B) Scatterplot of PTPA and ARL8B with the most significant positive correlation. (C) Scatterplot of UGP2 and TWSG1 with the most significant negative correlation. (D) Correlation heatmap between the 34 DEPs and five semen parameters
Fig. 4
Fig. 4
Interaction network analysis of differentially expressed proteins in seminal plasma. (A) Construction of the protein-protein interaction network. (B) Screening of hub proteins by MCODE and Cytohubba algorithms. (C) Functional enrichment analysis of common hub proteins
Fig. 5
Fig. 5
Verification of protein expression in the validation cohort. (A) Western blot showing protein abundances of GSTM2, ITLN1, PSAP, and β-actin in seminal plasma of COVID-19 (n = 7) and control (n = 7) groups. (B) Relative protein quantification of GSTM2, ITLN1, and PSAP levels normalized to β-actin. ** p < 0.01, *** p < 0.001
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