ArticleInternational journal of biological sciences2026
Single-cell atlas of rhesus monkey testis reveals aging- and season-dependent regulation of spermatogenesis and microenvironment homeostasis.
Article in International journal of biological sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Spermatogenesis is a highly orchestrated process that depends on precise coordination between germ cells and the testicular microenvironment. However, how intrinsic aging and seasonal transitions regulate this process in nonhuman primates remains poorly defined. Here we generate a single-cell transcriptomic atlas of the rhesus monkey testis spanning prepubertal, adult and aged stages across breeding and non-breeding seasons. We uncover pronounced seasonal oscillations in meiotic germ cells that coincide with remodeling of Sertoli-cell junctional programs, including tight- and adherens-junction components, supporting blood-testis barrier plasticity as a seasonally tuned layer associated with meiotic progression. Within the spermatogonial compartment, we identify a transcriptionally distinct, high-stemness undifferentiated spermatogonial state (U3) that is selectively enriched during the adult non-breeding season and progressively depleted with aging. U3 cells exhibit PDGF-associated signaling together with transcriptional programs linked to cytoskeletal organization and metabolic adaptation, consistent with a high-plasticity SSC state responsive to seasonal cues. Guided by these signatures, we establish a three-dimensional collagen-PDGF culture platform that enhances colony formation and supports extended propagation of rhesus SSCs in vitro. Finally, aging-associated shifts in testicular immune cell composition in rhesus monkeys were observed, including expanded CD3⁺CD4⁻CD8⁻ T-cell populations and pro-inflammatory macrophage profiles with diminished antigen-presentation signatures, and this phenotypic observation aligns with heightened inflammatory pressure on spermatogenic homeostasis. Collectively, this study delineates the age- and season-dependent regulation of spermatogenesis in rhesus monkeys, and provides new mechanistic insights into testicular aging and homeostasis.
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