A developmental and aging atlas of the killifish testis uncovers a mid-age inflection point

The turquoise killifish (Nothobranchius furzeri), a teleost with an exceptional short lifespan, provides a unique opportunity to interrogate testicular development and aging across the entire life. Using histology, proliferation assays, and transcriptomic profiling, we constructed a comprehensive developmental and aging atlas of killifish spermatogenesis.

We identify a rapid onset of testicular tissue development upon hatching, followed by a peak in cell-cycling activity. In turn, killifish testicular tissue undergoes pronounced mid-life transition that marks the principal inflection point in testicular aging, characterized by a sharp decline in proliferative activity and expansion of the interstitial space. This transition is accompanied by activation of extracellular matrix remodeling, angiogenic and inflammatory pathways, and by concomitant repression of mitotic, meiotic, and spermatogonial gene networks.