Insights into replicative senescence of human testicular peritubular cells

作者: Nina Schmid , Florian Flenkenthaler , Jan B. Stöckl , Kim-Gwendolyn Dietrich , Frank M. Köhn

DOI: 10.1038/S41598-019-51380-W

关键词: Stem cellMitochondrial DNATelomereBiologyMacrophage migration inhibitory factorLysosomeCell biologySenescenceProteostasisPopulation

摘要: There is evidence for an age-related decline in male reproductive functions, yet how the human testis may age not understood. Human testicular peritubular cells (HTPCs) transport sperm, contribute to spermatogonial stem cell (SSC) niche and immune surveillance, and can be isolated studied vitro. Consequences of replicative senescence HTPCs were evaluated gain partial insights into aging. To this end, early advanced HTPC passages, which was indicated by increased size, altered nuclear morphology, enhanced β-galactosidase activity, telomere attrition reduced mitochondrial DNA (mtDNA), compared. These alterations are typical senescent cells, general. examine HTPC-specific changes, focused ion beam scanning electron microscopy (FIB/SEM) tomography employed, revealed a network lysosome population. The results coincide with data parallel proteomic analysis indicate deranged proteostasis. mRNA levels contractility markers growth factors, important SSC niche, significantly altered. A secretome identified, however, elevated macrophage migration inhibitory factor (MIF) dipeptidyl peptidase 4 (DPP4), play role spermatogenesis. Testicular DPP4 further represent possible drug target.

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