Redox Homeostasis and Spermatogonial Stem Cell Aging: MolecularNetworks and Targeted Strategies of Antioxidant Interventions
QIU Xingyun1,2, FAN Yi3, LIU Bang1, ZHOU Dai1*
Male reproductive aging is a critical issue affecting fertility and reproductive health, which hasincreasingly attracted the attention of the academic community. The age-related decline in the function of SSCs(spermatogonial stem cells) is the fundamental basis of this reproductive decline. Current studies suggest that theabnormal accumulation of ROS (reactive oxygen species) not only directly damages SSCs but also impairs thetesticular microenvironment that supports their function, thereby disrupting the homeostasis between SSC self-renewal and differentiation. Focusing on the perspective of redox homeostasis, this review systematically outlines thepathological roles of ROS in the aging process of SSCs and summarizes the underlying mechanisms of endogenous and exogenous antioxidant interventions. Particular emphasis is placed on how antioxidants regulate the balancebetween cellular apoptosis and mitophagy through the crosstalk of signaling networks, including the Nrf2/Keap1,SIRT1/FOXO, and PI3K/Akt/mTOR pathways. Furthermore, given the dual properties of ROS as physiologicalsignaling molecules, this article objectively discusses the potential risk of “reductive stress” in antioxidant therapiesand explores the paradigm shift in intervention strategies from “simple scavenging” to “homeostasis reconstruction.” Finally, considering the physical restrictions imposed by the blood-testis barrier on drug delivery, the application potential of nano-targeted strategies in overcoming clinical translation challenges is briefly prospected. Thisreview aims to provide a theoretical reference for basic research and individualized clinical interventions in malereproductive aging.
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