Specific types of male infertility are correlated with T cell exhaustion or senescence signatures

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 () and Silvia Gregori ()
Additional contact information
Giada Amodio: IRCCS Ospedale San Raffaele
Giorgia Giacomini: IRCCS Ospedale San Raffaele
Luca Boeri: Department of Urology
Massimiliano Raffo: Division of Experimental Oncology/Unit of Urology; URI; IRCCS Ospedale San Raffaele
Simone Cilio: Division of Experimental Oncology/Unit of Urology; URI; IRCCS Ospedale San Raffaele
Edoardo Pozzi: Division of Experimental Oncology/Unit of Urology; URI; IRCCS Ospedale San Raffaele
Federico Belladelli: Division of Experimental Oncology/Unit of Urology; URI; IRCCS Ospedale San Raffaele
Fausto Negri: Division of Experimental Oncology/Unit of Urology; URI; IRCCS Ospedale San Raffaele
Anna Maria Ferrara: Division of Experimental Oncology/Unit of Urology; URI; IRCCS Ospedale San Raffaele
Alessia d’Arma: Division of Experimental Oncology/Unit of Urology; URI; IRCCS Ospedale San Raffaele
Francesca Romana Santoni de Sio: IRCCS Ospedale San Raffaele
Luca Pagliardini: IRCCS Ospedale San Raffaele
Enrico Papaleo: IRCCS Ospedale San Raffaele
Eugenio Ventimiglia: Division of Experimental Oncology/Unit of Urology; URI; IRCCS Ospedale San Raffaele
Massimo Alfano: Division of Experimental Oncology/Unit of Urology; URI; IRCCS Ospedale San Raffaele
Francesco Montorsi: Division of Experimental Oncology/Unit of Urology; URI; IRCCS Ospedale San Raffaele
Andrea Salonia: Division of Experimental Oncology/Unit of Urology; URI; IRCCS Ospedale San Raffaele
Silvia Gregori: IRCCS Ospedale San Raffaele

Nature Communications, 2025, vol. 16, issue 1, 1-17

Abstract: 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.

Date: 2025
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56193-2

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DOI: 10.1038/s41467-025-56193-2

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