Fetal hypoxia causes oocyte oxidative stress damage via the Sirt3/Sod2 pathway and can be alleviated by nicotinamide mononucleotide
6 affiliations
- 1Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, Qinghai 810001, China
- 2Institute of Animal Husbandry and Veterinary Medicine, Beijing Academy of Agriculture and Forestry Sciences, Beijing 100097, China
- 3State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing 100193, China
- 4Air Force Medical University, Air Force Medical Center, PLA, Beijing 100089, China
- 5University of Chinese Academy of Sciences, Beijing 100049, China
- 6Qinghai Key Laboratory of Animal Ecological Genomics, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, 810001 Qinghai, China
Abstract
Environmental hypoxia exerts detrimental effects on the reproductive capabilities of both humans and animals. A fetal hypoxia model was established in which fetal mice were kept in a high-plateau hypoxic setting from embryonic day (E) 0 to 16.5. In our previous research, we found that fetal hypoxia exposure perturbs the methylation of imprinted genes in adult sperm and causes intergenerational placental impairments in male offspring. However, the specific impacts of fetal hypoxia on the female reproductive system, particularly regarding oocyte maturation, remain poorly understood. First, we found that fetal hypoxia mice exhibited a significant reduction in the average number of pups per litter. We conducted a comprehensive analysis of the transcriptome in oocytes from the hypoxic group and investigated the metabolic alterations within the follicular microenvironment. Fetal hypoxic stress contributed to cleavage and blastocyst rate reduction and induced early apoptosis and DNA damage triggered by mitochondrial dysfunction, oxidative stress aggravation and Sirt3/Sod2 downregulation. Additionally, administration of nicotinamide mononucleotide (NMN) has been shown to prevent oocytes from mitochondrial dysfunction and developmental impairment by increasing the expression of Sirt3/Sod2 and autophagy. The number of pups per litter in fetal hypoxia mice was reduced by 57.7% compared to the control group, while NMN intervention could restore it to 73.1% of the control group. These results indicate that fetal hypoxia exposure exerts multiple potential damages to adult female reproduction, while highlighting the clinical potential of NMN supplementation as a targeted intervention to alleviate such hypoxia-associated female reproductive impairment.
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BibTeX
@article{zhang2026fetal,
title = {{Fetal hypoxia causes oocyte oxidative stress damage via the Sirt3/Sod2 pathway and can be alleviated by nicotinamide mononucleotide}},
author = {Lu-Yao Zhang and Ke-Xiong Liu and Ke Zhang and Xiang Qin and Yu-Wen Luo and Qing-Rui Zhuan and Jian Hou and Qi-En Yang and Yun-Peng Hou},
journal = {Zoological Research},
year = {2026},
month = sep,
doi = {10.24272/j.issn.2095-8137.2025.579},
url = {https://doi.org/10.24272/j.issn.2095-8137.2025.579},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Fetal hypoxia causes oocyte oxidative stress damage via the Sirt3/Sod2 pathway and can be alleviated by nicotinamide mononucleotide
AU - Lu-Yao Zhang
AU - Ke-Xiong Liu
AU - Ke Zhang
AU - Xiang Qin
AU - Yu-Wen Luo
AU - Qing-Rui Zhuan
AU - Jian Hou
AU - Qi-En Yang
AU - Yun-Peng Hou
PY - 2026
DA - 2026/09/18
JO - Zoological Research
DO - 10.24272/j.issn.2095-8137.2025.579
UR - https://doi.org/10.24272/j.issn.2095-8137.2025.579
AB - Environmental hypoxia exerts detrimental effects on the reproductive capabilities of both humans and animals. A fetal hypoxia model was established in which fetal mice were kept in a high-plateau hypoxic setting from embryonic day (E) 0 to 16.5. In our previous research, we found that fetal hypoxia exposure perturbs the methylation of imprinted genes in adult sperm and causes intergenerational placental impairments in male offspring. However, the specific impacts of fetal hypoxia on the female reproductive system, particularly regarding oocyte maturation, remain poorly understood. First, we found that fetal hypoxia mice exhibited a significant reduction in the average number of pups per litter. We conducted a comprehensive analysis of the transcriptome in oocytes from the hypoxic group and investigated the metabolic alterations within the follicular microenvironment. Fetal hypoxic stress contributed to cleavage and blastocyst rate reduction and induced early apoptosis and DNA damage triggered by mitochondrial dysfunction, oxidative stress aggravation and Sirt3/Sod2 downregulation. Additionally, administration of nicotinamide mononucleotide (NMN) has been shown to prevent oocytes from mitochondrial dysfunction and developmental impairment by increasing the expression of Sirt3/Sod2 and autophagy. The number of pups per litter in fetal hypoxia mice was reduced by 57.7% compared to the control group, while NMN intervention could restore it to 73.1% of the control group. These results indicate that fetal hypoxia exposure exerts multiple potential damages to adult female reproduction, while highlighting the clinical potential of NMN supplementation as a targeted intervention to alleviate such hypoxia-associated female reproductive impairment.
SN - 2095-8137
ER -