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Aging, inflammation and DNA damage in the somatic testicular niche with idiopathic germ cell aplasia

Author

Listed:
  • Massimo Alfano

    (URI, IRCCS Ospedale San Raffaele)

  • Anna Sofia Tascini

    (Center for Omics Sciences, IRCCS Ospedale San Raffaele)

  • Filippo Pederzoli

    (URI, IRCCS Ospedale San Raffaele
    Università Vita-Salute San Raffaele)

  • Irene Locatelli

    (URI, IRCCS Ospedale San Raffaele)

  • Manuela Nebuloni

    (L. Sacco Hospital, Università degli Studi di Milano)

  • Francesca Giannese

    (Center for Omics Sciences, IRCCS Ospedale San Raffaele)

  • Jose Manuel Garcia-Manteiga

    (Center for Omics Sciences, IRCCS Ospedale San Raffaele)

  • Giovanni Tonon

    (Center for Omics Sciences, IRCCS Ospedale San Raffaele)

  • Giada Amodio

    (IRCCS Ospedale San Raffaele)

  • Silvia Gregori

    (IRCCS Ospedale San Raffaele)

  • Alessandra Agresti

    (IRCCS Ospedale San Raffaele)

  • Francesco Montorsi

    (URI, IRCCS Ospedale San Raffaele
    Università Vita-Salute San Raffaele)

  • Andrea Salonia

    (URI, IRCCS Ospedale San Raffaele
    Università Vita-Salute San Raffaele)

Abstract

Molecular mechanisms associated with human germ cell aplasia in infertile men remain undefined. Here we perform single-cell transcriptome profiling to highlight differentially expressed genes and pathways in each somatic cell type in testes of men with idiopathic germ cell aplasia. We identify immaturity of Leydig cells, chronic tissue inflammation, fibrosis, and senescence phenotype of the somatic cells, as well markers of chronic inflammation in the blood. We find that deregulated expression of parentally imprinted genes in myoid and immature Leydig cells, with relevant changes in the ratio of Lamin A/C transcripts and an active DNA damage response in Leydig and peritubular myoid cells are also indicative of senescence of the testicular niche. This study offers molecular insights into the pathogenesis of idiopathic germ cell aplasia.

Suggested Citation

  • Massimo Alfano & Anna Sofia Tascini & Filippo Pederzoli & Irene Locatelli & Manuela Nebuloni & Francesca Giannese & Jose Manuel Garcia-Manteiga & Giovanni Tonon & Giada Amodio & Silvia Gregori & Aless, 2021. "Aging, inflammation and DNA damage in the somatic testicular niche with idiopathic germ cell aplasia," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25544-0
    DOI: 10.1038/s41467-021-25544-0
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