Therapeutics · Emerging Therapies
Abstract
The aim of the present study is to assess whether low level laser therapy (LLLT) can protect ovaries from chemotherapy-induced gonadotoxicity using a mice model of premature ovarian failure induced by cyclophosphamide (CTX). LLLT (64 J/cm2) increased the number of antral follicles whilst decreasing the number of atretic follicles compared to CTX alone. LLLT increased the number of primordial follicles compared with those in the CTX group but they did not differ from those in the control group. LLLT treatment increased the number of AMH-positive follicles compared to CTX alone. LLLT application increased ovarian weight, serum progesterone concentration and P450scc protein levels compared to CTX alone. LLLT reduced the apoptosis in antral follicles and the BAX/BCL-2 ratio compared to CTX alone. Vascular morphology, analysed by CD31 and α-SMA immunostaining, was restored in LLLT-treated ovaries compared to CTX alone. In conclusion, application of LLLT prior to CTX might serve as a promising and novel protocol to preserve female fertility in cancer survivors.
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Low level laser therapy (LLLT) modulates ovarian function in mature female mice
Oubiña G et al., 2019 · Progress in biophysics and molecular biology
It is known that LLLT has beneficial effects on several pathological conditions including wound healing, pain and inflammation. LLLT modulates biological processes, including cell proliferation, apoptosis and angiogenesis. In the present study, we examined the effect of local application of LLLT on follicular dynamics, ovarian reserve, AMH expression, progesterone levels, apoptosis, angiogenesis, and reproductive outcome in adult mice. LLLT (200 J/cm2) increased the percentage of primary and preantral follicles, whilst decreasing the percentage of corpora lutea compared to control ovaries. LLLT-treated ovaries did not exhibit any changes regarding the number of primordial follicles. We observed a higher percentage of AMH-positive follicles (in early stages of development) in LLLT-treated ovaries compared to control ovaries. LLLT reduced the P4 concentration and the apoptosis in early antral follicles compared to control ones. LLLT caused a reduction in the endothelial cell area and an increase in the periendothelial cell area in the ovary. Additionally, LLLT was able to improve oocyte quality. Our findings suggest that local application of LLLT modulates follicular dynamics by regulating apoptosis and the vascular stability in mouse ovary. In conclusion, these data indicate that LLLT might become a novel and useful tool in the treatment of several pathologies, including female reproductive disorders.
Related research
Has the time come to include low-level laser photobiomodulation as an adjuvant therapy in the treatment of impaired endometrial receptivity?
El Faham DA et al., 2018 · Lasers in medical science
Low-level laser therapy (LLLT) has been used in photobiomodulation to promote healing, regenerate, and restore tissue function. Women with persistent thin endometrium were assumed to encounter diminished activity in the regenerative and functional capacity of their endometrium. The aim of this study was to examine the ability of LLLT in 635 nm wavelength to enhance the proliferation and gene expression of in vitro cultured endometrial cells. Single (SE) versus multiple exposures (ME) to LLLT were examined in the study groups and compared to controls. A fluence dose of 4.27 J/cm2 for 16 min was given once in the SE or divided in three equal sessions in days 2, 4, and 6 of the culture in ME. Cellular response was evaluated by measuring viable cell numbers and surface area. Pattern of MUC1, ITGA5, ITGB3, LIF, and PTEN gene expression was assessed using the qRT-PCR. Greater numbers of cells were found in both study groups (P < 0.001) as compared to controls. The surface area of cells at the end of culture phase was highly significant (P < 0.001) in ME when compared to SE and controls. A statistically significant difference was found in terms of gene expression in both irradiated groups (P < 0.001) as compared to controls, although greater difference in PTEN tumour suppressor gene (Phosphatase and tensin homolog) expression was toward ME. The introduction of LLLT to the armamentarium of infertility will serve as a new adjuvant therapy in this field. The current study proofed that LLLT was able to increase the proliferative and functional capacity of cultured endometrial cells.
Photobiomodulation ameliorates ovarian aging by alleviating oxidative stress and inflammation damage and improving mitochondrial function
He Y et al., 2024 · Journal of photochemistry and photobiology. B, Biology
Ovarian aging is a serious clinical concern. Few safe and effective methods are currently available to improve ovarian functions. Photobiomodulation (PBM) is a safe and noninvasive physical therapy that can modulate a series of biological processes. Recently, several studies have noted its potential to improve the function of ovary and reproductive cells. However, the effects of PBM treatment on natural ovarian aging remain unclear. In this study, we used a naturally reproductive aging mouse model to observe the effect of PBM on ovarian function. Young and aged female ICR mice were treated with or without PBM for 2 months. PBM was performed using a semiconductor InGaAlP laser emitting at 650 nm (80 mW, 6.7 mW/cm2 for 5 or 10 min, resulting in a dose of 2 or 4 J/cm2, respectively). After treatment, the effects of PBM and its role in oxidative stress, inflammation, and mitochondrial function were investigated. We found that PBM (4 J/cm2) effectively recovered the levels of sex hormones, increased the number of primordial and growing follicles, improved angiogenesis, and decreased cell apoptosis in naturally aged mice. Moreover, PBM reduced oxidative stress, inhibited chronic ovarian inflammation, and improved mitochondrial function in aged ovaries. Similar protective effects of PBM were observed in a hydrogen peroxide-induced oxidative stress model of human granulosa cell line (KGN) in vitro. Increased cell viability, cell proliferation, hormone secretion, mitochondrial membrane potential, and adenosine triphosphate levels and decreased apoptosis and oxidative stress were detected in KGN cells after PBM treatment. Collectively, this study suggest that PBM treatment is beneficial for restoring ovarian function in naturally reproductive aging mice and has a significant protective effect against oxidative stress damage in KGN cells. The mechanisms underlying the benefits of PBM in ovarian aging include antioxidant stress, reduction of inflammation, and preservation of mitochondrial function. Therefore, this study emphasizes the potential of PBM as a therapeutic intervention to ameliorate ovarian aging.
How do red and infrared low-level lasers affect folliculogenesis cycle in rat's ovary tissue in comparison with clomiphene under in vivo condition
Naseri P et al., 2017 · Lasers in medical science
Folliculogenesis is a cycle that produces the majority of oocyte. Any disruption to this cycle leads to ovulation diseases, like polycystic ovarian syndrome (PCOS). Treatments include drugs and surgery; lasers have also been used complementarily. Meanwhile, still there is no definite treatment for PCOS. This study investigated the photo-bio stimulation effect of near-infrared and red low-level laser on producing follicles and compared the result with result of using common drug, clomiphene. Therefore, the aim of this study was to propose the use of lasers autonomously treatment. So, there was one question: how do lasers affect folliculogenesis cycle in rat's ovary tissue? In this study, 28 rats were assigned to four groups as follows: control (CT), clomiphene drug (D), red laser (RL), and near-infrared laser (NIRL). Afterwards, 14 rats of RL and NIRL groups received laser on the first 2 days of estrous cycle, each 6 days, for 48 days. During treatment period, each rat received energy density of 5 J/cm2. Seven rats in D group received clomiphene. After the experiment, lasers' effects at two wavelengths of 630 and 810 nm groups have been investigated and compared with clomiphene and CT groups. Producing different follicles to complement folliculogenesis cycle increased in NIRL and RL groups, but this increase was significant only in the NIRL group. This indicates that NIRL increases ovarian activity to produce oocyte that certainly can be used in future studies for finding a cure to ovarian negligence to produce more oocyte and treat diseases caused by it like PCOS.
630 nm LED phototherapy enhances ovarian function and fertility potential in advanced reproductive age females
Su T et al., 2026 · Bioengineering & translational medicine
Ovarian aging, a major contributor to declining fertility in women of advanced reproductive age (ARA), is strongly associated with impaired mitochondrial function within oocytes. Although current mitochondrial-targeted strategies can improve ovarian function, their clinical application remains limited by cost and side effects. In this study, 630 nm light-emitting diode (LED) phototherapy is shown to ameliorate ovarian aging phenotypes in ARA mice by enhancing mitochondrial complex II activity via upregulation of succinate dehydrogenase subunit B (SDHB). This intervention restores oocyte adenosine triphosphate (ATP) production, improves meiotic progression, and significantly increases blastocyst formation. To assess translational feasibility, a wearable 630 nm LED phototherapy device is developed and evaluated in a pilot clinical study in women with diminished ovarian reserve (DOR). After treatment, the antral follicle count (AFC) significantly increases from a median of 2 (IQR 1-5) to 6 (IQR 2-7; p = 0.011), and the number of oocytes retrieved showed a non-significant tendency to increase from 2 (IQR 1-5) to 5 (IQR 2-7; p = 0.083), indicating a potential improvement in ovarian reserve. These findings demonstrate that 630 nm LED phototherapy enhances mitochondrial function and oocyte competence, providing a promising non-invasive strategy to improve fertility in women affected by ovarian aging.