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Journal of Peking University (Health Sciences) ›› 2025, Vol. 57 ›› Issue (4): 627-632. doi: 10.19723/j.issn.1671-167X.2025.04.001

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Low-level laser therapy for the treatment of male infertility and erectile dysfunction

Yuanjie NIU1, Zhongcheng XIN1,2,*(), Guiting LIN3, Pan DING1, Jiancheng PAN1, Yuhong FENG1, Yinglu GUO2   

  1. 1. Male Reproductive and Sexual Medicine, Department of Urology, The Second Hospital of Tianjin Medical University; Tianjin Institute of Urology, Tianjin 300211, China
    2. Department of Urology, Peking University First Hospital, Beijing 100034, China
    3. Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA 94143-0738, USA
  • Received:2025-04-18 Online:2025-08-18 Published:2025-08-02
  • Contact: Zhongcheng XIN

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Abstract:

Low-level laser therapy (LLLT), a noninvasive photobiomodulation technique, employs red or near-infrared (NIR) light (600-1 000 nm) with power outputs ranging from 5 to 500 mW. It exerts therapeutic effects through molecular mechanisms, specifically the activation of cytochrome C oxidase (CCO) and the modulation of intracellular signaling pathways. By enhancing mitochondrial adenosine triphosphate (ATP) synthesis, LLLT mitigates oxidative stress, regulates the reactive oxygen species (ROS)/glutathione peroxidase (GSH-Px)/superoxide dismutase (SOD) axis, and activates key pathways, including phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK). These mechanisms confer antioxidant, anti-inflammatory, and pro-regenerative properties to LLLT, making it a viable intervention for dermatological conditions, oncological therapies, and musculoskeletal disorders. Recent preclinical studies underscore LLLT' s potential in male reproductive health. Specifically, it ameliorates cavernosal fibrosis and endothelial dysfunction in erectile dysfunction (ED) models by upregulating the PI3K/Akt and MAPK/ERK pathways. In the context of sperm biology, LLLT enhances motility and acrosomal integrity in both fresh and cryopreserved spermatozoa. This is achieved through mitochondrial metabolic reprogramming, such as CCO-mediated electron transport chain activation, redox homeostasis restoration, and epigenetic modulation involving DNA methylation and histone acetylation. Additionally, LLLT alleviates scrotal heat-induced oligospermia by promoting seminiferous epithelial differentiation, elevating serum testosterone levels, and suppressing lipid peroxidation. These findings highlight the translational potential of LLLT in regenerative medicine, particularly for male sexual and reproductive disorders. Future research efforts should focus on interdisciplinary collaborations spanning life sciences, engineering, and physics. The goal is to optimize laser parameters, including wavelength, irradiance, and treatment duration, and establish standardized protocols. Rigorous preclinical and clinical investigations are paramount to validate the safety, efficacy, and long-term outcomes of LLLT, ultimately paving the way for its integration into precision medicine frameworks for urological and reproductive therapies.

Key words: Low-level laser therapy, Photobiomodulation, Male infertility, Erectile dysfunction

CLC Number: 

  • R698

Table 1

Mechanisms of cellular signaling pathway regulation by multi-wavelength low-level laser"

Wavelength/nm Signaling pathway Biological effects Reference
904 Catalase Reduces ROS, promotes wound healing in diabetic mice [29]
635 NF-κB Reduces ROS, inhibits NF-κB, decreases PGE2, COX-1, and COX-2 expression, anti-inflammatory [30]
980 PI3K/Akt/Bcl-2 Regulates S-phase progression in osteoblasts [31]
910 MAPK/ERK Enhances cell migration and cytoskeletal remodeling [32]
808 Hedgehog (Ptch, Ihh, Smo, Gli) Promotes osteoblast proliferation [33]
650 NO/Ca2+/ROS Enhances sperm motility [34]
635 VEGF Reduces VEGF concentration, increases endothelial cell proliferation [35]
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