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

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 b...

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Published inBMC genomics Vol. 26; no. 1; pp. 281 - 12
Main Authors Huang, Jialyu, Su, Yufang, Wang, Jiawei, Fang, Zheng, Zhang, Yiwei, Chen, Hong, Wan, Xinxia, Xiong, Yuanhuan, Song, Ning, Chen, Houyang, Wu, Xingwu
Format Journal Article
LanguageEnglish
Published London BioMed Central 21.03.2025
BioMed Central Ltd
Springer Nature B.V
BMC
Subjects
Adult
Algorithms
Animal Genetics and Genomics
Annotations
Asymptomatic
Asymptomatic infection
Biological activity
Biomarkers
Biomedical and Life Sciences
Blood proteins
Comparative analysis
COVID-19
COVID-19 - complications
COVID-19 - metabolism
COVID-19 - physiopathology
Disease transmission
Enzymes
Fertility
Genes
Genomes
Genomics
Health aspects
Humans
Infection
Infections
Life Sciences
Male
Males
Mass spectrometry
Medical research
Medicine, Experimental
Microarrays
Microbial Genetics and Genomics
Middle Aged
Motility
Peptides
Plant Genetics and Genomics
Plasma
Protein Interaction Maps
Proteins
Proteome
Proteomics
Proteomics - methods
Quality control
Reproductive organs, Male
RNA
SARS-CoV-2
Scientific imaging
Semen
Semen - metabolism
Seminal plasma
Severe acute respiratory syndrome coronavirus 2
Software
Solvents
Sperm
Sperm Count
Spermatogenesis
Type 2 diabetes
China
United States
United States > US
COVID-19
SARS-CoV-2
Seminal plasma
Proteomics
Online AccessGet full text
ISSN1471-2164
1471-2164
DOI10.1186/s12864-025-11473-5

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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.
AbstractList A considerable proportion of males suffer from asymptomatic SARS-CoV-2 infection, while the effect on reproductive function and underlying pathomechanisms remain unclear. 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. 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.
A considerable proportion of males suffer from asymptomatic SARS-CoV-2 infection, while the effect on reproductive function and underlying pathomechanisms remain unclear. 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. 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.
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, SARS-CoV-2, Seminal plasma, Proteomics
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.
A considerable proportion of males suffer from asymptomatic SARS-CoV-2 infection, while the effect on reproductive function and underlying pathomechanisms remain unclear.BACKGROUNDA considerable proportion of males suffer from asymptomatic SARS-CoV-2 infection, while the effect on reproductive function and underlying pathomechanisms remain unclear.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.RESULTSThe 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.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.CONCLUSIONSIn 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.
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.
BackgroundA considerable proportion of males suffer from asymptomatic SARS-CoV-2 infection, while the effect on reproductive function and underlying pathomechanisms remain unclear.ResultsThe 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.ConclusionsIn 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.
ArticleNumber 281
Audience Academic
Author Song, Ning
Wang, Jiawei
Chen, Hong
Chen, Houyang
Wu, Xingwu
Huang, Jialyu
Su, Yufang
Fang, Zheng
Zhang, Yiwei
Wan, Xinxia
Xiong, Yuanhuan
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/40119256$$D View this record in MEDLINE/PubMed
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Issue 1
Keywords COVID-19
SARS-CoV-2
Seminal plasma
Proteomics
Language English
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Snippet Background A considerable proportion of males suffer from asymptomatic SARS-CoV-2 infection, while the effect on reproductive function and underlying...
A considerable proportion of males suffer from asymptomatic SARS-CoV-2 infection, while the effect on reproductive function and underlying pathomechanisms...
Background A considerable proportion of males suffer from asymptomatic SARS-CoV-2 infection, while the effect on reproductive function and underlying...
BackgroundA considerable proportion of males suffer from asymptomatic SARS-CoV-2 infection, while the effect on reproductive function and underlying...
Abstract Background A considerable proportion of males suffer from asymptomatic SARS-CoV-2 infection, while the effect on reproductive function and underlying...
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StartPage 281
SubjectTerms Adult
Algorithms
Animal Genetics and Genomics
Annotations
Asymptomatic
Asymptomatic infection
Biological activity
Biomarkers
Biomedical and Life Sciences
Blood proteins
Comparative analysis
COVID-19
COVID-19 - complications
COVID-19 - metabolism
COVID-19 - physiopathology
Disease transmission
Enzymes
Fertility
Genes
Genomes
Genomics
Health aspects
Humans
Infection
Infections
Life Sciences
Male
Males
Mass spectrometry
Medical research
Medicine, Experimental
Microarrays
Microbial Genetics and Genomics
Middle Aged
Motility
Peptides
Plant Genetics and Genomics
Plasma
Protein Interaction Maps
Proteins
Proteome
Proteomics
Proteomics - methods
Quality control
Reproductive organs, Male
RNA
SARS-CoV-2
Scientific imaging
Semen
Semen - metabolism
Seminal plasma
Severe acute respiratory syndrome coronavirus 2
Software
Solvents
Sperm
Sperm Count
Spermatogenesis
Type 2 diabetes
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Title Seminal plasma proteomics of asymptomatic COVID-19 patients reveals disruption of male reproductive function
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