Disturbance in Testosterone Production in Leydig Cells by Polycyclic Aromatic Hydrocarbons

Oh, Seunghoon

doi:10.12717/dr.2014.18.4.187

Cited by 19 publications

(10 citation statements)

References 57 publications

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“…In Leydig cells from vertebrates, similar disorders to those we described in the ADG cells from mussels in this work have been identified as pathologic: abnormal enlargement, changes in shape, and internal structure and foamy appearance of cytoplasm due to proliferation of lipid droplets (lipidosis) (Creasy and Foster, 2002;Dietrich and Krieger, 2009;Cheng, 2014). Lipidosis of Leydig cells has been related to their degeneration and with disturbance of their function (Chung et al, 2011;Oh, 2014). The Leydig cells function is the biosynthesis of testosterone, which indirectly regulates spermatogenesis in a complex cascade of chemical interactions with Sertoli and germ cells, resulting in feedback regulation of testosterone synthesis.…”

Section: Cell Injuriessupporting

confidence: 62%

Gonadal Histopathological Disorders in Mytilus galloprovincialis Male Exposed to Tars Used in Mussel Farms

et al. 2019

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Polycyclic aromatic hydrocarbons (PAHs) and trace metals are pollutants widely distributed in the marine environment with toxic effects on live organisms, but few laboratory studies have proved their causal relationship with histopathologic alterations from invertebrates. We analyse the histopathologic effects of a tar mixture used in mussel farms on the gonad of male mussels. Mussels were exposed to water-accommodated fractions from different sub-lethal concentrations of that tar mixture during different times. The accumulation of PAHs and metals in mussels was quantified in each one tar exposure condition, and a comparative histological and morphometric analysis of the male gonad was performed, as well as of the gametogenic disorders and the cellular pathologies induced. Spermatogenesis disruption and alterations of somatic and germinal cells were observed as a direct effect of treatment. The pathologies observed followed an increasing malignity sequence depending on dose and exposure time: spawning induction; arrest of spermatogenesis and spermiogenesis; suppression of immune response; dysplasia of Sertoli and connective cells and finally, severe disorders of germinal cells. We demonstrate for the first time that tar used in waterproofing of floating rafts from the mussel farms causes severe effects on male mussel gonad, constituting a direct risk to the health of these organisms, affecting gametogenesis, quality of gametes and, ultimately, the sustainability of this resource and their quality for human consumption. Moreover, we propose the pathologies described in mussel as biomarkers of marine pollution and the mussel gonad as study model of testicular toxicity mechanisms in male reproduction.

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Section: Cell Injuriessupporting

confidence: 62%

Gonadal Histopathological Disorders in Mytilus galloprovincialis Male Exposed to Tars Used in Mussel Farms

et al. 2019

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“…In this study, the BTB disruption could be a potential reason for PM 2.5 ‐caused reproductive dysfunction in male rat thus led to less sperm. Meanwhile, PM 2.5 is a complex compound composes of many endocrine‐disrupting chemical such as polycyclic aromatic hydrocarbons that influences the endocrine system at the hormone level, such as testicular testosterone by inhibiting 3 beta‐hydroxysteroid dehydrogenase (3β‐HSD) and steroidogenic acute regulatory protein (StAR) . Testosterone is curial for spermatogenesis and integrity of BTB .…”

Section: Discussionmentioning

confidence: 99%

“…Meanwhile, PM 2.5 is a complex compound composes of many endocrine-disrupting chemical such as polycyclic aromatic hydrocarbons 21 that influences the endocrine system at the hormone level, such as testicular testosterone by inhibiting 3 beta-hydroxysteroid dehydrogenase (3b-HSD) and steroidogenic acute regulatory protein (StAR). 45 Testosterone is curial for spermatogenesis and integrity of BTB. 46,47 Toxicological studies have shown that specific knockout of androgen receptors (ARs) in Sertoli and Leydig cells could result in infertility in mice.…”

Section: Pm 25 Activated P38 Mapk Signaling In Testes Of Ratsmentioning

confidence: 99%

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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“…7,12‐Dimethylbenz[α]anthracene (DMBA) is a PAH found in high concentrations in the tar fraction of cigarette smoke and car exhaust in addition to benzo[α]pyrene . DMBA has been widely reported to induce immunotoxicity as an immune suppressor in laboratory animal models and extensively used as an experimental model carcinogen for skin, breast, oral, lung, and other cancers .…”

Section: Introductionmentioning

confidence: 99%

7,12‐Dimethylbenz[α]anthracene increases cell proliferation and invasion through induction of Wnt/β‐catenin signaling and EMT process

Kwon

Baek

et al. 2018

Environmental Toxicology

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7,12-Dimethylbenz[α]anthracene (DMBA) is a hazardous component present in polluted environments. DMBA has been used as an experimental tool for in vivo tumor formation owing to its carcinogenic effects, but the detailed molecular mechanism of DMBA has not been fully established. To comprehend the carcinogenic mechanism of DMBA, we explored its effects in the breast cancer cell lines, MCF-7 and MDA-MB-231, and the cervical cancer cell line, HeLa. Cell viability assay and measurement of a proliferation marker showed that DMBA markedly increased cancer cell proliferation. Furthermore, morphological observations and wound healing assays in nontumorigenic MCF-10A cells and trans-well invasion assays in cancer cells following DMBA treatment revealed that DMBA induced cell migration and invasion. To reveal the molecular mechanism of DMBA, we investigated the effects of DMBA on the epithelial-mesenchymal transition (EMT) process and Wnt/β-catenin signaling, a critical pathway for cell proliferation that was reported to correlate with the EMT process, by using quantitative RT-PCR (qPCR), western blot analysis, and confocal microscopy. Consequently, we found that DMBA increased cancer cell proliferation and invasion through the promotion of EMT-inducing factors and β-catenin. Especially, it was revealed in promoter activity assay using mutated luciferase vectors on transcription factor-binding sites that TWIST1 is promoted by DMBA through induction of STAT3-mediated promoter activation. To further elucidate the detailed mechanism of DMBA, we aimed to identify the key regulator of its carcinogenic action. DMBA was shown to significantly upregulate the expression of specificity protein 1 (Sp1), a transcription factor, and the carcinogenic effects of DMBA were blocked via the suppression or interruption of Sp1 activity. In conclusion, our data suggested that DMBA induced carcinogenic effects through activation of Wnt/β-catenin signaling and the EMT process by upregulating Sp1 activity.

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Disturbance in Testosterone Production in Leydig Cells by Polycyclic Aromatic Hydrocarbons

Cited by 19 publications

References 57 publications

Gonadal Histopathological Disorders in Mytilus galloprovincialis Male Exposed to Tars Used in Mussel Farms

Gonadal Histopathological Disorders in Mytilus galloprovincialis Male Exposed to Tars Used in Mussel Farms

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

7,12‐Dimethylbenz[α]anthracene increases cell proliferation and invasion through induction of Wnt/β‐catenin signaling and EMT process

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