Notch pathway is required for protection against heat-stress in spermatogonial stem cells

Abstract

Environmentally favorable conditions the sustainability of spermatogenesis is brought about by a balance between two types of division, the self-renewal division for the maintenance of the stem cell pool and the differentiation division for continuous production of spermatozoa. The production of gametes under unfavorable, stressful conditions can decrease or even be interrupted, compromising fertility parameters. Thus, the survival of spermatogonial stem cells (SSCs) is crucial for the recovery of spermatogenesis after stressful situations (e.g. high temperature). Here, we show that the Notch pathway protects the spermatogonial stem cells against thermal stress, ensuring reproductive success after normal conditions are restored. First, presenilin enhancer-2 (pen-2), the catalytic subunit of {gamma}-secretase complex, was localized in SSCs of the medaka testis. The exposure of adult males to thermal stress condition induced apoptosis in all spermatogenics cells, with the exception of SSCs. Concomitantly, the Notch pathways was up-regulated, including the pen-2, its ligands (dll4, jag1-2) and its receptors (notch1a-3); pen-2 expression was restricted to the SSCs during thermal stress. The importance of this pathway was further supported by an ex vivo approach, in which the inhibition of Notch activity induced a loss of SSCs. Overall, this study demonstrates that the Notch pathways activity is necessary for the protection of SSCs under chronic thermal stress.