Urban fine particulate matter exposure causes male reproductive injury through destroying blood-testis barrier (BTB) integrity

Cao, Xining; Shen, Lianju; Wu, Shengde; Yan, Chao; Zhou, Yue; Geng, Xin; Wang, Yang-cai; Yang, Liu; Liu, Bo; Tang, Xiangliang; Guo, Min; Liu, Dongyao; Chen, Long; Sun, Mei; He, Dalin; Lin, Tao; Wei, Guanghui

doi:10.1016/j.toxlet.2016.12.004

Cited by 75 publications

(33 citation statements)

References 44 publications

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“…The results indicated that the damage of testicular BTB integrality could cause the male reproductive toxicity. The previous studies showed that the exposure to PM 2.5 could cause BTB integrity disruption in rat and Zhang et al reported that sulfur dioxide (an environmental toxicants) could destroy the integrity of BTB ultrastructure, which is similar to our results. The results mean that PM 2.5 could induce the male reproductive toxicity through damaging the BTB integrality.…”

Section: Discussionsupporting

confidence: 92%

“…These results suggested that spermatogenesis may be influenced by PM 2.5 exposure. This is similar to the finding of Cao et al, which showed that PM 2.5 could damage the testicular and epididymal tissue structures of rats after inhalation exposure . Spermatogenesis orderly proceeds in the microenvironment composed of BTB.…”

Section: Discussionsupporting

confidence: 91%

“…Moreover, the decreasing of testosterone resulted in the detachment of developing spermatids from SCs in the seminiferous epithelium, demonstrating that testosterone is important in cell adhesion . PM 2.5 , with ability of inducing SC impairment and inhibiting testosterone production, has been considered as an endocrine disruptor . Luteinizing hormone is glycol‐protein hormones secreted by the anterior pituitary and act directly on the testis to stimulate somatic cellular functions in support of spermatogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…Study of Radwan et al showed that PM exposure could decrease the level of testosterone in human . Recent studies have proved that PM 2.5 could impair blood–testis barrier (BTB) integrity thought reducing expressions of tight junction, adherens junction, and gap junction proteins in testicular tissue, followed by oxidative stress . As a result, the reproductive system is the critical target of PM 2.5 .…”

Section: Introductionmentioning

confidence: 99%

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Fine particle matter disrupts the blood–testis barrier by activating TGF‐β3/p38 MAPK pathway and decreasing testosterone secretion in rat

Liu

Ren

Wei

et al. 2018

Environmental Toxicology

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Fine particle matter (PM) is correlated with male reproductive dysfunction in animals and humans, but the underlying mechanisms remain unknown. To investigate the toxic mechanism of PM, 32 male Sprague-Dawley (SD) rats were exposed to saline or PM with the doses of 1.8, 5.4, and 16.2 mg/kg.b.w. via intratracheal instillation, respectively, one time every 3 days, in total times for 30 days. Sperm concentration, hormone level, the expressions of BTB-associated protein and the mitogen-activated protein kinase (MAPK) pathway, tumor necrosis factor α and transforming growth factor β3 levels were detected. The results showed a decrease in sperm number, testosterone and luteinizing hormone levels and altered ultrastructure of BTB in testis of rat after exposure to PM . The protein levels of N-Cadherin, Occludin, Claudin-11, and Connexin-43 were significantly decreased in the testes. TGF-β3 content in testes showed increase, with the p-p38/p38 MAPK ratio also increasing after PM exposure. These results demonstrate that PM restrained the expressions of BTB-associated proteins through activating TGF-β3/p38 MAPK pathway and decreasing testosterone secretion, and therefore lead to the damage of BTB resulting in the decrease of sperm quality, which might be the potential reasons for its negative effects on spermatogenesis and male reproduction.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Fine particle matter disrupts the blood–testis barrier by activating TGF‐β3/p38 MAPK pathway and decreasing testosterone secretion in rat

Liu

Ren

Wei

et al. 2018

Environmental Toxicology

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“…A 20 μL volume of the suspension was transferred into 4 mL of fresh physiological saline (200‐fold dilution) and incubated in a 37°C water bath for 1 h. One drop of the diluted sperm suspension was transferred to a counting chamber of an improved Neubauer hemocytometer. Then, the sperm were counted under a light microscope at ×100 magnification according to the practical methods for sperm counting …”

Section: Methodsmentioning

confidence: 99%

Di‐(2‐ethylhexyl) phthalate (DEHP)‐induced testicular toxicity through Nrf2‐mediated Notch1 signaling pathway in Sprague–Dawley rats

Tang

Shen

et al. 2018

Environmental Toxicology

Self Cite

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Di-(2-ethylhexyl) phthalate (DEHP) is an environmental endocrine disruptor widely used in China that is harmful to the male reproductive system. Many studies have shown that DEHP causes testicular toxicity through oxidative stress, but the specific mechanism is unknown. Because the Notch pathway is a key mechanism for regulating cell growth and proliferation, we investigated whether Notch is involved in DEHP-induced testicular toxicity and whether vitamins E and C could rescue testicular impairment in Sprague-Dawley (SD) rats. Compared with the control group, we found that DEHP exposure induced testicular toxicity through oxidative stress injury, and it decreased the testosterone level (P < .01) and upregulated nuclear factor-erythroid 2 related factor (Nrf2) expression (P < .01). Therefore, because oxidative stress might be the initiating factor of DEHP-induced testicular toxicity, treatment with the antioxidant vitamins E and C activated the Notch1 signaling pathway in the testis and in Leydig cells. Treatment with vitamins E and C normalized the oxidative stress state after DEHP exposure and restored testicular development to be similar to the control group. In summary, antioxidant vitamins E and C may be used to treat DEHP-induced testicular toxicity.

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Luteolin Ameliorates Testis Injury and Blood–Testis Barrier Disruption through the Nrf2 Signaling Pathway and by Upregulating Cx43

Zhang

Zhu

et al. 2019

Molecular Nutrition Food Res

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Scope: Luteolin, a natural flavonoid, displays protective activities to testicular tissue. However, the molecular mechanisms are still unclear. In this study, the aim is to identify the protective effects and underlying mechanisms of luteolin against triptolide (TP)-induced damage of testicular tissue. Methods and results: Pre-incubation of Sertoli cells (SCs) with luteolin results in a significant reduction of TP-induced apoptotic cells, which occurs concomitantly with the effective inhibition of reactive oxygen species accumulation. Luteolin results in a significant reduction in testicular damage and spermatogenesis dysfunction in a mouse model of testicular damage. Mechanistic studies reveal that luteolin significantly triggers Nrf2 translocation, increases antioxidant response element-luciferase reporter activity, and induces antioxidant enzyme expression. Nrf2 siRNA reduces luteolin-induced protection in SCs. Besides inhibiting apoptosis, luteolin recovers the blood-testis barrier (BTB) integrity by upregulating connexin43 (Cx43) expression. Moreover, specifically blocked Cx43 activity completely blocks repairmen of luteolin to BTB values. In accordance with in vitro results, luteolin suppresses testicular injury and spermatogenesis dysfunction by activation of Nrf2 and Cx43 in a testicular injury model. Conclusion:Luteolin is identified as a novel active ingredient that contributes to the protective activity in testicular damage through activating the Nrf2 signaling pathway and by upregulating Cx43.

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Urban fine particulate matter exposure causes male reproductive injury through destroying blood-testis barrier (BTB) integrity

Cited by 75 publications

References 44 publications

Fine particle matter disrupts the blood–testis barrier by activating TGF‐β3/p38 MAPK pathway and decreasing testosterone secretion in rat

Fine particle matter disrupts the blood–testis barrier by activating TGF‐β3/p38 MAPK pathway and decreasing testosterone secretion in rat

Di‐(2‐ethylhexyl) phthalate (DEHP)‐induced testicular toxicity through Nrf2‐mediated Notch1 signaling pathway in Sprague–Dawley rats

Luteolin Ameliorates Testis Injury and Blood–Testis Barrier Disruption through the Nrf2 Signaling Pathway and by Upregulating Cx43

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