Heat stress in spermatogenesis: a redox‐dependent decision network linking ROS, autophagy, and regulated cell death
- 1Instituto de Biodiversidade e Sustentabilidade (NUPEM) Universidade Federal do Rio de Janeiro (UFRJ) Av. Amaro Reinaldo dos Santos Silva, 764, São José do Barreto Macaé RJ 27965‐045 Brazil
- 2Programa de Pós‐Graduação em Ciência e Biotecnologia (PPBI) Universidade Federal Fluminense Rua Professor Marcos Waldemar de Freitas Reis, Bloco M, sala 229C São Domingos Niterói CEP 24210‐201 RJ Brazil
Abstract
Heat stress (HS) is an increasing threat to male reproductive health, disrupting spermatogenesis through complex and interdependent cellular responses within the seminiferous epithelium. Although excessive reactive oxygen species (ROS) production is a hallmark of HS, ROS also act as central regulators of cell fate decisions beyond their role in oxidative damage. Here, we propose a unified framework in which spermatogenic outcomes under HS are governed by a redox‐dependent decision network, whereby ROS dynamics determine the balance between adaptive responses and regulated cell death (RCD). At moderate levels, ROS activate cytoprotective mechanisms, including antioxidant defences and autophagy, thereby promoting proteostasis and preserving cellular homeostasis. In contrast, excessive or sustained ROS accumulation induces lipid peroxidation, mitochondrial dysfunction, and impaired autophagic flux, driving the transition toward interconnected RCD pathways, including apoptosis, ferroptosis, and pyroptosis. Autophagy emerges as a central regulatory checkpoint in this network, acting as a molecular rheostat that modulates the shift between adaptation and cell death. Importantly, HS effects are stage‐specific across spermatogenesis. Spermatogonia exhibit relative resilience due to efficient redox buffering and autophagic competence, whereas spermatocytes represent a critical vulnerability point, marked by heightened oxidative sensitivity and a strong propensity toward apoptosis. Post‐meiotic germ cells are particularly susceptible to disruptions in structural remodelling and membrane integrity, while Sertoli cells act as key regulators of the redox microenvironment and amplifiers of HS‐induced damage. Finally, we highlight redox balance modulation as a promising strategy to mitigate HS‐induced reproductive damage. However, effective antioxidant interventions must be precisely calibrated to preserve physiological redox signalling and autophagic function rather than indiscriminately suppress ROS. Together, this framework provides a mechanistic basis for understanding how HS regulates germ cell fate and identifies potential targets for preserving male fertility under environmental and physiological thermal stress.
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BibTeX
@article{batista2026heat,
title = {{Heat stress in spermatogenesis: a redox‐dependent decision network linking ROS, autophagy, and regulated cell death}},
author = {Ribrio Ivan Tavares Pereira Batista},
journal = {Biological Reviews of the Cambridge Philosophical Society},
year = {2026},
month = jul,
doi = {10.1002/brv.70200},
url = {https://doi.org/10.1002/brv.70200},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Heat stress in spermatogenesis: a redox‐dependent decision network linking ROS, autophagy, and regulated cell death
AU - Ribrio Ivan Tavares Pereira Batista
PY - 2026
DA - 2026/07/10
JO - Biological Reviews of the Cambridge Philosophical Society
DO - 10.1002/brv.70200
UR - https://doi.org/10.1002/brv.70200
AB - Heat stress (HS) is an increasing threat to male reproductive health, disrupting spermatogenesis through complex and interdependent cellular responses within the seminiferous epithelium. Although excessive reactive oxygen species (ROS) production is a hallmark of HS, ROS also act as central regulators of cell fate decisions beyond their role in oxidative damage. Here, we propose a unified framework in which spermatogenic outcomes under HS are governed by a redox‐dependent decision network, whereby ROS dynamics determine the balance between adaptive responses and regulated cell death (RCD). At moderate levels, ROS activate cytoprotective mechanisms, including antioxidant defences and autophagy, thereby promoting proteostasis and preserving cellular homeostasis. In contrast, excessive or sustained ROS accumulation induces lipid peroxidation, mitochondrial dysfunction, and impaired autophagic flux, driving the transition toward interconnected RCD pathways, including apoptosis, ferroptosis, and pyroptosis. Autophagy emerges as a central regulatory checkpoint in this network, acting as a molecular rheostat that modulates the shift between adaptation and cell death. Importantly, HS effects are stage‐specific across spermatogenesis. Spermatogonia exhibit relative resilience due to efficient redox buffering and autophagic competence, whereas spermatocytes represent a critical vulnerability point, marked by heightened oxidative sensitivity and a strong propensity toward apoptosis. Post‐meiotic germ cells are particularly susceptible to disruptions in structural remodelling and membrane integrity, while Sertoli cells act as key regulators of the redox microenvironment and amplifiers of HS‐induced damage. Finally, we highlight redox balance modulation as a promising strategy to mitigate HS‐induced reproductive damage. However, effective antioxidant interventions must be precisely calibrated to preserve physiological redox signalling and autophagic function rather than indiscriminately suppress ROS. Together, this framework provides a mechanistic basis for understanding how HS regulates germ cell fate and identifies potential targets for preserving male fertility under environmental and physiological thermal stress.
SN - 1464-7931
SN - 1469-185X
ER -