Porcine Sertoli Cell-Derived Exosomes Drive Spermatogonial Stem Cell differentiation through PSMD11-p38 MAPK-Mediated Redox Signaling
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ABSTRACT: Spermatogonial stem cell fate decisions-self-renewal versus differentiation-are orchestrated by complex intercellular communication within the testicular niche. While paracrine signaling has been extensively characterized, the role of extracellular vesicles, especially in livestock, remains poorly understood. Here we demonstrate that primary porcine Sertoli cell-derived exosomes constitute a previously unrecognized regulatory mechanism controlling SSC differentiation through redox homeostasis. Using an ex vivo porcine testicular culture system that recapitulates the native SSC microenvironment, we show that porcine Sertoli cell exosomes promote SSC differentiation, evidenced by decreased expression of stemness markers (GFRA1, UCHL1) and increased differentiation markers (KIT, STRA8). Proteomic profiling revealed enrichment of antioxidant enzymes (SOD1, SOD2, CAT etc.,) within these exosomes. Mechanistically, PSMD11 was identified as a novel regulatory protein within the exosome to modulate SSC redox balance via the p38 MAPK pathway. The differentiation of porcine SSCs was impaired by PSMD11 knockdown, while was recovered by exogenous PSMD11, confirming its functional significance. These findings establish exosome-mediated redox regulation as a fundamental mechanism governing SSC fate decisions, with implications for understanding male fertility, developing therapeutic strategies for azoospermia, and improving reproductive efficiency in agricultural species.
INSTRUMENT(S): Orbitrap Fusion
ORGANISM(S): Sus Scrofa (ncbitaxon:9823)
SUBMITTER:
Kang Zou
PROVIDER: MSV000098563 | MassIVE | Sat Jul 19 03:49:00 BST 2025
SECONDARY ACCESSION(S): PXD066323
REPOSITORIES: MassIVE
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