Dietary Patterns Modulate Ozone-Induced Reproductive Injury in C57BL/6J Mice.
- 1Department of Toxicology, Joint International Research Laboratory of Environment and Health, Ministry of Education, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China.
Abstract
Dietary patterns orchestrate systemic metabolism and reproductive health, yet whether specific dietary patterns modulate susceptibility to ozone-induced male reproductive toxicity and its intergenerational consequences remains unclear. Here, male C57BL/6J mice were fed ad libitum (AL), a 30% calorie-restricted diet (CR), or a 45% high-fat diet (HFD), followed by ozone exposure (1 ppm, 4 h/day, 5 days/week for 3 months) to recapitulate real-world condition. We found that ozone exposure exacerbated reproductive injury under both CR and HFD, each diet perturbing metabolism through distinct pathways. Under CR, ozone further suppressed glycolysis, the TCA cycle, and amino acid metabolism, resulting in severe testicular energy depletion and impaired spermatogenic differentiation. In contrast, HFD amplified ozone-induced metabolic overload, inflammatory activation, and mitochondrial stress, accompanied by dysregulated lipid metabolism. Integrated metabolomic analyses identified disruption of the glucose-lactate-TCA axis as a central mechanism underlying testicular energy failure. Furthermore, exposed males (F0) were subsequently mated with unexposed females to generate offspring (F1 and F2) for assessment of next-generation health risks. The results showed that paternal dietary regimen and ozone exposure exclusively perturbed metabolic homeostasis in F1 offspring, indicating a reversible metabolic reprogramming rather than stable transgenerational inheritance. Collectively, these findings establish systemic metabolic status as a critical determinant of ozone-induced reproductive toxicity and reveal that paternal nutritional and environmental challenges jointly prime metabolic susceptibility in the next generation (F1).
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BibTeX
@article{guo2026dietary,
title = {{Dietary Patterns Modulate Ozone-Induced Reproductive Injury in C57BL/6J Mice.}},
author = {Yuzhi Guo and Shen Chen and Jiahao Zhang and Miao Li and Xinhang Jiang and Yahan Yang and Lizhu Ye and Zhaohuan Gui and Guanghui Dong and Daochuan Li and Wen Chen},
journal = {Environment \& health (Washington, D.C.)},
year = {2026},
month = jun,
doi = {10.1021/envhealth.5c00865},
url = {https://europepmc.org/article/MED/42903743},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Dietary Patterns Modulate Ozone-Induced Reproductive Injury in C57BL/6J Mice.
AU - Yuzhi Guo
AU - Shen Chen
AU - Jiahao Zhang
AU - Miao Li
AU - Xinhang Jiang
AU - Yahan Yang
AU - Lizhu Ye
AU - Zhaohuan Gui
AU - Guanghui Dong
AU - Daochuan Li
AU - Wen Chen
PY - 2026
DA - 2026/06/02
JO - Environment & health (Washington, D.C.)
DO - 10.1021/envhealth.5c00865
UR - https://europepmc.org/article/MED/42903743
AB - Dietary patterns orchestrate systemic metabolism and reproductive health, yet whether specific dietary patterns modulate susceptibility to ozone-induced male reproductive toxicity and its intergenerational consequences remains unclear. Here, male C57BL/6J mice were fed ad libitum (AL), a 30% calorie-restricted diet (CR), or a 45% high-fat diet (HFD), followed by ozone exposure (1 ppm, 4 h/day, 5 days/week for 3 months) to recapitulate real-world condition. We found that ozone exposure exacerbated reproductive injury under both CR and HFD, each diet perturbing metabolism through distinct pathways. Under CR, ozone further suppressed glycolysis, the TCA cycle, and amino acid metabolism, resulting in severe testicular energy depletion and impaired spermatogenic differentiation. In contrast, HFD amplified ozone-induced metabolic overload, inflammatory activation, and mitochondrial stress, accompanied by dysregulated lipid metabolism. Integrated metabolomic analyses identified disruption of the glucose-lactate-TCA axis as a central mechanism underlying testicular energy failure. Furthermore, exposed males (F0) were subsequently mated with unexposed females to generate offspring (F1 and F2) for assessment of next-generation health risks. The results showed that paternal dietary regimen and ozone exposure exclusively perturbed metabolic homeostasis in F1 offspring, indicating a reversible metabolic reprogramming rather than stable transgenerational inheritance. Collectively, these findings establish systemic metabolic status as a critical determinant of ozone-induced reproductive toxicity and reveal that paternal nutritional and environmental challenges jointly prime metabolic susceptibility in the next generation (F1).
SN - 2833-8278
ER -