Specific types of male infertility are correlated with T cell exhaustion or senescence signatures
Abstract The association between male infertility and health status has yet to be unraveled. Here, by combining multiparameter phenotyping and scRNA-seq, we delineate the immune status of infertile men both at the semen and systemic levels. We first observe that young infertile men have a pro-inflam...
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| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56193-2 |
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| author | Giada Amodio Giorgia Giacomini Luca Boeri Massimiliano Raffo Simone Cilio Edoardo Pozzi Federico Belladelli Fausto Negri Anna Maria Ferrara Alessia d’Arma Francesca Romana Santoni de Sio Luca Pagliardini Enrico Papaleo Eugenio Ventimiglia Massimo Alfano Francesco Montorsi Andrea Salonia Silvia Gregori |
| author_facet | Giada Amodio Giorgia Giacomini Luca Boeri Massimiliano Raffo Simone Cilio Edoardo Pozzi Federico Belladelli Fausto Negri Anna Maria Ferrara Alessia d’Arma Francesca Romana Santoni de Sio Luca Pagliardini Enrico Papaleo Eugenio Ventimiglia Massimo Alfano Francesco Montorsi Andrea Salonia Silvia Gregori |
| author_sort | Giada Amodio |
| collection | DOAJ |
| description | Abstract The association between male infertility and health status has yet to be unraveled. Here, by combining multiparameter phenotyping and scRNA-seq, we delineate the immune status of infertile men both at the semen and systemic levels. We first observe that young infertile men have a pro-inflammatory milieu with increased frequency of myeloid cells and inflammatory mediators in the seminal fluid and the peripheral blood, which are immune alterations typically observed in healthy elderly men. Transcriptomic profiling confirms the upregulation of genes associated with the interferon-gamma and -alpha responses in peripheral blood T cells of infertile men with oligo-astheno-teratozoospermia or non-obstructive azoospermia, with distinct T cell signatures of exhaustion and senescence discriminating the two infertile conditions. These findings provide evidence that subtypes of male infertility are characterized by specific immune signatures and unravel the potential link between infertility and the risk of developing secondary diseases. |
| format | Article |
| id | doaj-art-50b8f1a691cb40cdb466b29172d55557 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-50b8f1a691cb40cdb466b29172d555572025-01-26T12:40:51ZengNature PortfolioNature Communications2041-17232025-01-0116111710.1038/s41467-025-56193-2Specific types of male infertility are correlated with T cell exhaustion or senescence signaturesGiada Amodio0Giorgia Giacomini1Luca Boeri2Massimiliano Raffo3Simone Cilio4Edoardo Pozzi5Federico Belladelli6Fausto Negri7Anna Maria Ferrara8Alessia d’Arma9Francesca Romana Santoni de Sio10Luca Pagliardini11Enrico Papaleo12Eugenio Ventimiglia13Massimo Alfano14Francesco Montorsi15Andrea Salonia16Silvia Gregori17San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS Ospedale San RaffaeleSan Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS Ospedale San RaffaeleIRCCS Fondazione Ca’ Granda Ospedale Maggiore Policlinico, Department of UrologyDivision of Experimental Oncology/Unit of Urology; URI; IRCCS Ospedale San RaffaeleDivision of Experimental Oncology/Unit of Urology; URI; IRCCS Ospedale San RaffaeleDivision of Experimental Oncology/Unit of Urology; URI; IRCCS Ospedale San RaffaeleDivision of Experimental Oncology/Unit of Urology; URI; IRCCS Ospedale San RaffaeleDivision of Experimental Oncology/Unit of Urology; URI; IRCCS Ospedale San RaffaeleDivision of Experimental Oncology/Unit of Urology; URI; IRCCS Ospedale San RaffaeleDivision of Experimental Oncology/Unit of Urology; URI; IRCCS Ospedale San RaffaeleSan Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS Ospedale San RaffaeleReproductive Sciences Laboratory, Obstetrics and Gynaecology Unit, IRCCS Ospedale San RaffaeleReproductive Sciences Laboratory, Obstetrics and Gynaecology Unit, IRCCS Ospedale San RaffaeleDivision of Experimental Oncology/Unit of Urology; URI; IRCCS Ospedale San RaffaeleDivision of Experimental Oncology/Unit of Urology; URI; IRCCS Ospedale San RaffaeleDivision of Experimental Oncology/Unit of Urology; URI; IRCCS Ospedale San RaffaeleDivision of Experimental Oncology/Unit of Urology; URI; IRCCS Ospedale San RaffaeleSan Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS Ospedale San RaffaeleAbstract The association between male infertility and health status has yet to be unraveled. Here, by combining multiparameter phenotyping and scRNA-seq, we delineate the immune status of infertile men both at the semen and systemic levels. We first observe that young infertile men have a pro-inflammatory milieu with increased frequency of myeloid cells and inflammatory mediators in the seminal fluid and the peripheral blood, which are immune alterations typically observed in healthy elderly men. Transcriptomic profiling confirms the upregulation of genes associated with the interferon-gamma and -alpha responses in peripheral blood T cells of infertile men with oligo-astheno-teratozoospermia or non-obstructive azoospermia, with distinct T cell signatures of exhaustion and senescence discriminating the two infertile conditions. These findings provide evidence that subtypes of male infertility are characterized by specific immune signatures and unravel the potential link between infertility and the risk of developing secondary diseases.https://doi.org/10.1038/s41467-025-56193-2 |
| spellingShingle | Giada Amodio Giorgia Giacomini Luca Boeri Massimiliano Raffo Simone Cilio Edoardo Pozzi Federico Belladelli Fausto Negri Anna Maria Ferrara Alessia d’Arma Francesca Romana Santoni de Sio Luca Pagliardini Enrico Papaleo Eugenio Ventimiglia Massimo Alfano Francesco Montorsi Andrea Salonia Silvia Gregori Specific types of male infertility are correlated with T cell exhaustion or senescence signatures Nature Communications |
| title | Specific types of male infertility are correlated with T cell exhaustion or senescence signatures |
| title_full | Specific types of male infertility are correlated with T cell exhaustion or senescence signatures |
| title_fullStr | Specific types of male infertility are correlated with T cell exhaustion or senescence signatures |
| title_full_unstemmed | Specific types of male infertility are correlated with T cell exhaustion or senescence signatures |
| title_short | Specific types of male infertility are correlated with T cell exhaustion or senescence signatures |
| title_sort | specific types of male infertility are correlated with t cell exhaustion or senescence signatures |
| url | https://doi.org/10.1038/s41467-025-56193-2 |
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