Protective Effect of Hyperbaric Oxygen Therapy on Female Reproductive Function Damage in High-Altitude Hypoxic Environments

doi:10.12280/gjszjk.20260192

Abstract

Abstract:

High-altitude hypoxic environment can impair female reproductive function through multiple pathological mechanisms. Continuous hypoxic exposure can induce oxidative stress and mitochondrial dysfunction, activate the body's inflammatory responses, disrupt the endocrine balance of the hypothalamic-pituitary-gonadal axis, and abnormally trigger cellular autophagy. These pathological changes collectively damage the normal tissue structures of the ovaries and uterus, inhibit follicle growth and development, reduce endometrial receptivity, and lead to the decreased fertility and the increased risk of adverse pregnancy outcomes in women living at high altitudes. Hyperbaric oxygen therapy, as a safe and effective physical intervention, alleviates hypoxia in the body by increasing the blood oxygen pressure and the oxygen concentration in blood and tissues. Through multiple mechanisms including improving oxidative stress and mitochondrial function, inhibiting inflammatory responses, regulating the hypothalamic-pituitary-gonadal axis, suppressing cell apoptosis, and promoting tissue repair, it effectively mitigates the damage to the female reproductive function caused by high-altitude hypoxia. Therefore, hyperbaric oxygen therapy provides a new intervention idea and feasible strategy for protecting female reproductive health in high-altitude regions.

Key words: Hypoxia, Altitude sickness, Hyperbaric oxygenation, Genital diseases, female, Oxidative stress

YANG Jiao, YANG Kai-li, GAO Ting, HAN Xue, WANG Ling. Protective Effect of Hyperbaric Oxygen Therapy on Female Reproductive Function Damage in High-Altitude Hypoxic Environments[J]. Journal of International Reproductive Health/Family Planning, 2026, 45(5): 418-424.

References 42

[1]	Zhong Y, Liu F, Zhang X, et al. Research progress on reproductive system damage caused by high altitude hypoxia[J]. Endocrine, 2024, 83(3):559-570. doi: 10.1007/s12020-023-03643-w. pmid: 38170433
[2]	Feng J, Zhu C, Zou J, et al. Hyperbaric Oxygen Therapy for the Treatment of Bone-Related Diseases[J]. Int J Mol Sci, 2025, 26(3):1067. doi: 10.3390/ijms26031067.
[3]	Xiong Z, Liu X, Wang Q. High-altitude hypoxia exposure alters follicular metabolome and oocyte developmental potential in women[J]. Arch Gynecol Obstet, 2025, 311(4):1051-1061. doi: 10.1007/s00404-024-07695-9.
[4]	荣长仙, 付冲, 黄楠, 等. 抗缪勒管激素、雌二醇、窦卵泡数对不同海拔女性卵巢储备功能的临床研究[J]. 中国妇产科临床杂志, 2023, 24(1):89-90. doi: 10.13390/j.issn.1672-1861.2023.01.031.
[5]	张晓静, 钟艳, 牟宏芳, 等. 枸杞多糖改善高原低氧环境雌性大鼠生殖损伤的机制研究[J]. 四川大学学报(医学版), 2024, 55(6):1477-1484. doi: 10.12182/20241160203.
[6]	Atykanov A, Imetkulova Z, Abdurakhmanova A, et al. Changes in reproductive system in Indian female students in middle altitude conditions[J]. JBRA Assist Reprod, 2026, 30(1):112-119. doi: 10.5935/1518-0557.20250167.
[7]	Ammar AY, Minisy FM, Shawki HH, et al. Exposure to a Low-Oxygen Environment Causes Implantation Failure and Transcriptomic Shifts in Mouse Uteruses and Ovaries[J]. Biomedicines, 2024, 12(5):1016. doi: 10.3390/biomedicines12051016.
[8]	Pena E, El Alam S, Siques P, et al. Oxidative Stress and Diseases Associated with High-Altitude Exposure[J]. Antioxidants(Basel), 2022, 11(2):267. doi: 10.3390/antiox11020267.
[9]	Shi YQ, Zhu XT, Zhang SN, et al. Premature ovarian insufficiency: a review on the role of oxidative stress and the application of antioxidants[J]. Front Endocrinol(Lausanne), 2023, 14:1172481. doi: 10.3389/fendo.2023.1172481.
[10]	Sharma S, Singh Y, Sandhir R, et al. Mitochondrial DNA mutations contribute to high altitude pulmonary edema via increased oxidative stress and metabolic reprogramming during hypobaric hypoxia[J]. Biochim Biophys Acta Bioenerg, 2021, 1862(8):148431. doi: 10.1016/j.bbabio.2021.148431.
[11]	Aiken CE, Tarry-Adkins JL, Spiroski AM, et al. Chronic gestational hypoxia accelerates ovarian aging and lowers ovarian reserve in next-generation adult rats[J]. FASEB J, 2019, 33(6):7758-7766. doi: 10.1096/fj.201802772R. pmid: 30888848
[12]	Xie Q, Hong W, Li Y, et al. Chitosan oligosaccharide improves ovarian granulosa cells inflammation and oxidative stress in patients with polycystic ovary syndrome[J]. Front Immunol, 2023, 14:1086232. doi: 10.3389/fimmu.2023.1086232.
[13]	Luo Z, Tian M, Yang G, et al. Hypoxia signaling in human health and diseases: implications and prospects for therapeutics[J]. Signal Transduct Target Ther, 2022, 7(1):218. doi: 10.1038/s41392-022-01080-1.
[14]	Rahman MA, Jalouli M, Bhajan SK, et al. The Role of Hypoxia-Inducible Factor-1α (HIF-1α) in the Progression of Ovarian Cancer: Perspectives on Female Infertility[J]. Cells, 2025, 14(6):437. doi: 10.3390/cells14060437.
[15]	Xiong S, Liu Z, Yao J, et al. HIF-1α regulated GLUT1-mediated glycolysis enhances Treponema pallidum-induced cytokine responses[J]. Cell Commun Signal, 2025, 23(1):219. doi: 10.1186/s12964-025-02211-1. pmid: 40346557
[16]	Shirafuji A, Orisaka M, Shimizu-Mizuno N, et al. Pro-inflammatory cytokines disrupt in vitro preantral follicle development by targeting granulosa and theca cell functions[J]. Front Endocrinol(Lausanne), 2025, 16:1667019. doi: 10.3389/fendo.2025.1667019.
[17]	Zhang J, Guo S, Dou B, et al. High-Altitude Hypoxia Injury: Systemic Mechanisms and Intervention Strategies on Immune and Inflammatory Responses[J]. Antioxidants(Basel), 2025, 15(1):36. doi: 10.3390/antiox15010036.
[18]	Xie Q, Kang Y, Zhang C, et al. The Role of Kisspeptin in the Control of the Hypothalamic-Pituitary-Gonadal Axis and Reproduction[J]. Front Endocrinol(Lausanne), 2022, 13:925206. doi: 10.3389/fendo.2022.925206.
[19]	Liu W, Pu L, Deng B, et al. Intermittent hypobaric hypoxia causes deleterious effects on the reproductive system in female rats[J]. Biomed Pharmacother, 2020, 130:110511. doi: 10.1016/j.biopha.2020.110511. pmid: 32679462
[20]	Ding M, Lu Y, Huang X, et al. Acute hypoxia induced dysregulation of clock-controlled ovary functions[J]. Front Physiol, 2022, 13:1024038. doi: 10.3389/fphys.2022.1024038.
[21]	Pan Y, Wu G, Chen M, et al. Lactate Promotes Hypoxic Granulosa Cells' Autophagy by Activating the HIF-1α/BNIP3/Beclin-1 Signaling Axis[J]. Genes(Basel), 2024, 16(1):14. doi: 10.3390/genes16010014.
[22]	Zhang L, Liu K, Liu Z, et al. In pre-clinical study fetal hypoxia caused autophagy and mitochondrial impairment in ovary granulosa cells mitigated by melatonin supplement[J]. J Adv Res, 2024, 64:15-30. doi: 10.1016/j.jare.2023.11.008.
[23]	Liang Z, Guo Q, Zheng Z, et al. Hypoxia-inducible factor 1α inhibitor reduces hippocampal neuronal ferroptosis[J]. Neural Regen Res, 2026, 21(6):2389-2396. doi: 10.4103/NRR.NRR-D-24-01007.
[24]	Tang Z, Xu R, Zhang Z, et al. HIF-1α Protects Granulosa Cells From Hypoxia-Induced Apoptosis During Follicular Development by Inducing Autophagy[J]. Front Cell Dev Biol, 2021, 9:631016. doi: 10.3389/fcell.2021.631016.
[25]	Young HY, Lee S, Choi YE, et al. Hyperbaric oxygen increases mitochondrial biogenesis and function with oxidative stress in HL-1 cardiomyocytes[J]. J Appl Physiol(1985), 2025, 138(6):1490-1504. doi: 10.1152/japplphysiol.00428.2024.
[26]	Zhao H, Zhang T, Wang Y, et al. Early Hyperbaric Oxygen Therapy Promotes Recovery of Blunt Liver Injury in Rats via Inhibiting Inflammatory Response and Oxidative Stress[J]. Int J Med Sci, 2025, 22(9):2174-2185. doi: 10.7150/ijms.109842. pmid: 40303491
[27]	Sakas R, Dan K, Edelman D, et al. Hyperbaric Oxygen Therapy Alleviates Memory and Motor Impairments Following Traumatic Brain Injury via the Modulation of Mitochondrial-Dysfunction-Induced Neuronal Apoptosis in Rats[J]. Antioxidants(Basel), 2023, 12(12):2034. doi: 10.3390/antiox12122034.
[28]	Hsu HT, Yang YL, Chang WH, et al. Hyperbaric Oxygen Therapy Improves Parkinson's Disease by Promoting Mitochondrial Biogenesis via the SIRT-1/PGC-1α Pathway[J]. Biomolecules, 2022, 12(5):661. doi: 10.3390/biom12050661.
[29]	Ortega MA, Fraile-Martinez O, García-Montero C, et al. A General Overview on the Hyperbaric Oxygen Therapy: Applications, Mechanisms and Translational Opportunities[J]. Medicina(Kaunas), 2021, 57(9):864. doi: 10.3390/medicina57090864.
[30]	Lindenmann J, Kamolz L, Graier W, et al. Hyperbaric Oxygen Therapy and Tissue Regeneration: A Literature Survey[J]. Biomedicines, 2022, 10(12):3145. doi: 10.3390/biomedicines10123145.
[31]	Sunshine MD, Bindi VE, Nguyen BL, et al. Oxygen therapy attenuates neuroinflammation after spinal cord injury[J]. J Neuroinflammation, 2023, 20(1):303. doi: 10.1186/s12974-023-02985-6.
[32]	Yang L, Zhu HZ, Xie L, et al. Neuroprotective effects of hyperbaric oxygen therapy on vascular cognitive impairment in hypoperfused mice via miR-137-3p/TRAF3 pathway[J]. Transl Psychiatry, 2025, 15(1):537. doi: 10.1038/s41398-025-03771-z.
[33]	Xia A, Huang H, You W, et al. The neuroprotection of hyperbaric oxygen therapy against traumatic brain injury via NF-κB/MAPKs-CXCL1 signaling pathways[J]. Exp Brain Res, 2022, 240(1):207-220. doi: 10.1007/s00221-021-06249-8.
[34]	Guo Y, Liu J, Du X, et al. ROS exhaustion reverses the effects of hyperbaric oxygen on hemorrhagic transformation through reactivating microglia in post-stroke hyperglycemic mice[J]. Sci Rep, 2024, 14(1):21410. doi: 10.1038/s41598-024-72454-4. pmid: 39271781
[35]	Lampiasi N, Russo R. HIF-1α as a Central Regulator of Monocyte Responses to Hypoxia[J]. Biology(Basel), 2026, 15(3):213. doi: 10.3390/biology15030213.
[36]	Wang J, Yu W, Zhang Y, et al. Mechanism of hyperbaric oxygen therapy downregulating H-type angiogenesis in subchondral bone of knee osteoarthritis through the PHD2/HIF-1α pathway[J]. J Orthop Surg Res, 2025, 20(1):79. doi: 10.1186/s13018-025-05514-8. pmid: 39844325
[37]	王淼. 芬吗通联合高压氧治疗对早发性卵巢功能不全患者改良Kupperman积分、性激素及抗苗勒管激素水平的影响[J]. 实用妇科内分泌电子杂志, 2023, 10(30):72-74. doi: 10.3969/j.issn.2095-8803.2023.30.023.
[38]	Yu J, Qi YL, Lu DW, et al. Multiple Protocols Combined with Hyperbaric Oxygen Therapy on the Maintenance of Ovarian Function in Patients After Ovarian Cystectomy[J]. Front Surg, 2022, 9:877114. doi: 10.3389/fsurg.2022.877114.
[39]	Awad-Igbaria Y, Ferreira N, Keadan A, et al. HBO treatment enhances motor function and modulates pain development after sciatic nerve injury via protection the mitochondrial function[J]. J Transl Med, 2023, 21(1):545. doi: 10.1186/s12967-023-04414-x. pmid: 37582750
[40]	王芳芳, 王楠, 袁恒荣, 等. 高压氧疗法对神经退行性疾病的作用机制及应用研究进展[J]. 生理学报, 2025, 77(2):318-326. doi: 10.13294/j.aps.2025.0033.
[41]	Sánchez-Rodríguez EC, López VJ. Hypoxic ischemic encephalopathy (HIE)[J]. Front Neurol, 2024, 15:1389703. doi: 10.3389/fneur.2024.1389703.
[42]	Fu Q, Duan R, Sun Y, et al. Hyperbaric oxygen therapy for healthy aging: From mechanisms to therapeutics[J]. Redox Biol, 2022, 53:102352. doi: 10.1016/j.redox.2022.102352.