Exposure to 2,4-dichlorophenoxyacetic acid induces oxidative stress and apoptosis in mouse testis

Zhang, Dalei; Wu, Yaling; Yuan, Yangyang; Liu, Wenwen; Kuang, Haibin; Yang, Jianhua; Yang, Bei; Wu, Lei; Wu, Zhongze; Xu, Chao-Jiang

doi:10.1016/j.pestbp.2016.10.006

Cited by 20 publications

(7 citation statements)

References 33 publications

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“…44 There was oxidative stress in the testis of mice exposed to 2,4-D, resulting in the decrease of SOD activity and the increase of MDA content in serum. 45 Our results showed that the serum content of MDA in 2,4-D-exposed rats increased, while the activities of SOD and GSH-Px decreased, which indicated that the antioxidant ability was weakened and the lipid peroxidation was enhanced, which caused the body to enter a state of oxidative stress, potentially affecting the spermatogenic function in rat testis. Under normal physiological conditions, the production and clearance of ROS are maintained and regulated by oxidation and antioxidant systems in organisms.…”

Section: Discussionmentioning

confidence: 61%

“…SOD and GSH‐Px are important markers for the antioxidant capacity of the body 44 . There was oxidative stress in the testis of mice exposed to 2,4‐D, resulting in the decrease of SOD activity and the increase of MDA content in serum 45 . Our results showed that the serum content of MDA in 2,4‐D‐exposed rats increased, while the activities of SOD and GSH‐Px decreased, which indicated that the antioxidant ability was weakened and the lipid peroxidation was enhanced, which caused the body to enter a state of oxidative stress, potentially affecting the spermatogenic function in rat testis.…”

Section: Discussionmentioning

confidence: 99%

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Mechanism of 2,4‐Dichlorophenoxyacetic acid‐induced damage to rat testis via Fas/FasL pathway and the protective effect of Lycium barbarum polysaccharides

Zhou

Wang

et al. 2022

Environmental Toxicology

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The herbicide 2,4-Dichlorophenoxyacetic acid (2,4-D) is widely used to control broadleaved weeds and has been associated with male infertility. We studied the molecular mechanisms of 2,4-D induced male reproductive system damage and the protective effects of Lycium barbarum polysaccharides (LBP) using Sprague Dawley rats and TM4 cells. Treatment with 2,4-D caused architectural and functional changes in the testis, including collapsed and atrophied seminiferous tubules with reduced number of spermatozoa, scarce sperm in the epididymal duct, low levels of serum testosterone, decreased superoxide dismutase and glutathione peroxidase activity, high malondialdehyde content, and increased apoptosis in the testis and epididymis. The expression of Fas, FasL, FADD, Pro-caspase-8, Cleaved-Caspase-8, Pro-Caspase-3, and Cleaved-Caspase-3 were significantly increased in the testicular tissue of 2,4-D-treated rats. The proliferative activity of TM4 cells decreased with an increase in dose and time of 2,4-D exposure, along with enhanced Fas/Fas ligand expression and a decreased concentration of inhibin B in TM4 cell culture medium. Depletion of Fas by specific shRNA transfection reversed the effects of 2,4-D in TM4 cells, further confirming the involvement of death receptor pathway in 2,4-Dmediated apoptosis of sertoli cells. Treatment with LBP also reversed the effects of 2,4-D in testicular cells, resulting in improved cell architecture along with enhanced proliferative capacity. Moreover, in response to LBP treatment of Sertoli cells, the content of inhibin B increased, the level of reactive oxygen species and malondialdehyde decreased, the activities of superoxide dismutase and glutathione peroxidase increased, and the rate of apoptosis as well as the expression of Fas/Fas ligand signaling pathway proteins decreased.

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Section: Discussionmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Mechanism of 2,4‐Dichlorophenoxyacetic acid‐induced damage to rat testis via Fas/FasL pathway and the protective effect of Lycium barbarum polysaccharides

Zhou

Wang

et al. 2022

Environmental Toxicology

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“…The number of conjugated bonds in the structure of astaxanthin is related to its strong antioxidant function, which allows it to effectively remove oxygen free radicals from ovarian tissue and reduce body damage [ 31 ]. Under normal conditions, a certain amount of reactive oxygen species is produced in the follicles, and these molecules play an important role in follicle development and ovulation [ 32 ]. Dietary supplementation with astaxanthin improves antioxidant capacity and reduces oxidative damage in the ovary during gonad development in tilapia.…”

Section: Discussionmentioning

confidence: 99%

Role of Astaxanthin as a Stimulator of Ovarian Development in Nile Tilapia (Oreochromis niloticus) and Its Potential Regulatory Mechanism: Ameliorating Oxidative Stress and Apoptosis

Qiang

Tao

et al. 2022

Aquaculture Nutrition

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A 60-day feeding experiment was performed to evaluate the effect of dietary astaxanthin on gonad development, the antioxidant system, and its inherent mechanism in female Nile tilapia (Oreochromis niloticus). Fish were fed with diets containing astaxanthin at five levels [0 mg/kg (control), 50 mg/kg, 100 mg/kg, 150 mg/kg, and 200 mg/kg]. At the end of experiment, the group fed with 150 mg/kg astaxanthin showed significantly increased specific growth rate, feed utilization, viscerosomatic index, and hepatosomatic index compared with the control group ( P < 0.05 ). Gonad development was stimulated in the groups fed with 100 mg/kg and 150 mg/kg astaxanthin, and their gonadosomatic index and egg diameter were significantly higher than those of the control group and the group fed with 200 mg/kg astaxanthin. The ovaries of females in the groups fed with 100 mg/kg and 150 mg/kg astaxanthin were fully developed, the eggs were gray-yellow and uniform in size, and a large number of oocytes developed to stages IV and V. The serum levels of 17 β-estradiol, follicle-stimulating hormone, and luteinizing hormone were significantly higher in the groups fed with 100 mg/kg and 150 mg/kg astaxanthin than in the group fed with 200 mg/kg astaxanthin. Compared with the control and the other groups, the group fed with 150 mg/kg astaxanthin showed significantly higher transcript levels of genes encoding hormone receptors and higher catalase activity in ovarian tissues, lower malondialdehyde content, decreased apoptosis (reduced granulosa cell apoptosis and lower transcript levels of bax and caspase-3), and reduced follicular atresia. Gene ontology analyses revealed that cell division and the cell cycle were enriched with differentially expressed genes in the group fed with 150 mg/kg astaxanthin, compared with the control group. We concluded that dietary astaxanthin at a concentration of 150 mg/kg activates follicle development by inhibiting expression of mapk1 (involved in MAPK signaling) and increasing the expression genes involved in oocyte meiosis (chp2, ppp3ca, map2k1, and smc1a1) and progesterone-mediated oocyte maturation (igf1, plk1, and cdk1). In conclusion, female Nile tilapia fed with 150 mg/kg astaxanthin showed increased growth, reduced oxidative stress in ovarian tissue, lower levels of cell apoptosis, and improved oocyte development.

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“…Apoptosis, an indispensable process during normal spermatogenesis, is closely related to the lipid peroxidation of spermatogenic cells (De Rooij & Janssen, 1987). On the other hand, spermatogonia that are damaged by oxidative stress due to nutritional and environmental factors are also cleared by apoptosis (Zhang et al, 2012(Zhang et al, , 2017.…”

Section: Discussionmentioning

confidence: 99%

“…As a key enzyme for the metabolism of unsaturated fatty acids, 12/15‐Lox interacts between unsaturated fatty acid oxidation and lipophilic antioxidants and determined the redox state of cell membranes (Singh & Rao, 2019). Moreover, apoptosis is closely related to the lipid peroxidation of spermatogenic cells (Wang, Zeng, et al, 2016; Zhang et al, 2017). However, little information is available to explain the role of GPX4‐12/15‐Lox‐mediated apoptosis in GC2‐spd cell activity.…”

Section: Introductionmentioning

confidence: 99%

The effects of selenium on GPX4‐mediated lipid peroxidation and apoptosis in germ cells

Liu

Zhu

Yuan

et al. 2021

J of Applied Toxicology

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Emerging evidence suggests that selenium plays an essential role in sperm maturation.However, the specific signaling pathway by which selenium exerts effect has not been elucidated. To evaluate the effect of selenium on GPX4-mediated lipid peroxidation and apoptosis in germ cells, selenium deficiency was modeled by culturing GC2-spd cells in serum-free medium. Treatment with 0.5-μM sodium selenite (NaSe) or 5.0-μM selenomethionine (SeMet) significantly improved the proliferation rate and GPX4 protein expression after selenium deficiency. Moreover, NaSe and SeMet decreased the MDA content and lipid peroxidation. When adenovirus was used to knockdown the expression of the GPX4 gene (shRNA-GPX4), the early apoptosis rate of the shRNA-GPX4 cells was significantly higher than that of the EGFP cells. Increased expression of Caspase3 and Bax, as well as MDA content were observed in the shRNA-GPX4 cells compared with EGFP cells. In further, overexpression of the GPX4 gene (ORF-GPX4) cells exhibited increased cell proliferation and decreased MDA content. However, there was no significant difference in 12/15-lox expression both in ORF-GPX4 cells and shRNA-GPX4 cells. Conclusively, GPX4 was involved in the regulation of lipid peroxidation and apoptosis in GC2-spd cells. Selenium played a role in promoting cell proliferation by mediating GPX4. The regulation of GPX4 may occur independently of 12/15-Lox. These findings confirmed the effect of selenium on spermatogenesis and offered a potential target for treating abnormal semen quality in men.

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Exposure to 2,4-dichlorophenoxyacetic acid induces oxidative stress and apoptosis in mouse testis

Cited by 20 publications

References 33 publications

Mechanism of 2,4‐Dichlorophenoxyacetic acid‐induced damage to rat testis via Fas/FasL pathway and the protective effect of Lycium barbarum polysaccharides

Mechanism of 2,4‐Dichlorophenoxyacetic acid‐induced damage to rat testis via Fas/FasL pathway and the protective effect of Lycium barbarum polysaccharides

Role of Astaxanthin as a Stimulator of Ovarian Development in Nile Tilapia (Oreochromis niloticus) and Its Potential Regulatory Mechanism: Ameliorating Oxidative Stress and Apoptosis

The effects of selenium on GPX4‐mediated lipid peroxidation and apoptosis in germ cells

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