Protective Effect of Resveratrol on Benzo(a)Pyrene Induced Dysfunctions of Steroidogenesis and Steroidogenic Acute Regulatory Gene Expression in Leydig Cells
Benzo(a)pyrene [B(a)P] is the toxic environmental Polycyclic Aromatic Hydrocarbon (PAH), that exerts male reproductive dysfunctions. In this study the molecular mechanism of B(a)P induced Leydig cell steroidogenic dysfunctions and its protective mechanism of action with a natural Aryl hydrocarbon re...
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Frontiers Media S.A.
2019-04-01
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Online Access: | https://www.frontiersin.org/article/10.3389/fendo.2019.00272/full |
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author | Bhaswati Banerjee Supriya Chakraborty Pratip Chakraborty Debidas Ghosh Kuladip Jana |
author_facet | Bhaswati Banerjee Supriya Chakraborty Pratip Chakraborty Debidas Ghosh Kuladip Jana |
author_sort | Bhaswati Banerjee |
collection | DOAJ |
description | Benzo(a)pyrene [B(a)P] is the toxic environmental Polycyclic Aromatic Hydrocarbon (PAH), that exerts male reproductive dysfunctions. In this study the molecular mechanism of B(a)P induced Leydig cell steroidogenic dysfunctions and its protective mechanism of action with a natural Aryl hydrocarbon receptor (AhR) antagonist and anti-oxidant, Resveratrol (Res) has been investigated. B(a)P exposure induced ROS mediated steroidogenic imbalance via activation of p38MAPK and repression of testosterone level as well as other steroidogenic enzymes like CYPIIA1, 3β-HSD, 17β-HSD expressions. B(a)P exposure decreased StAR protein expression along with increased DAX-1, a transcriptional repressor of StAR gene. Along with that B(a)P decreased the expression of SF-1 that acts as a transcriptional inducer of StAR gene expression. The study has established Resveratrol as a potential agent combating the deleterious effect of B(a)P on Leydig cell steroidogenesis. Resveratrol treatment resulted significant protection against B(a)P by scavenging ROS and modulating the transcriptional regulation of anti-oxidant enzymes. Furthermore, Resveratrol also prevented stress kinase like p38 MAPK activation and increased StAR protein expression through the reduction of DAX-1 expression. Moreover, the testosterone production was efficiently restored with Resveratrol treatment. ChIP assay also revealed that resveratrol improved SF-1expression which further increased the StAR gene expression. Resveratrol acted efficiently against B(a)P, through its anti-oxidative properties as well as inhibits p38MAPK and increased steroidogenesis and StAR expression through the modulation of SF-1 gene expression. |
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language | English |
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spelling | doaj.art-6082ff5d86e24b0f9c2322f4c419d9732022-12-22T01:48:30ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922019-04-011010.3389/fendo.2019.00272446453Protective Effect of Resveratrol on Benzo(a)Pyrene Induced Dysfunctions of Steroidogenesis and Steroidogenic Acute Regulatory Gene Expression in Leydig CellsBhaswati Banerjee0Supriya Chakraborty1Pratip Chakraborty2Debidas Ghosh3Kuladip Jana4Division of Molecular Medicine, Bose Institute, Calcutta Improvement Trust Scheme VIIM, Kolkata, IndiaDivision of Molecular Medicine, Bose Institute, Calcutta Improvement Trust Scheme VIIM, Kolkata, IndiaDepartment of Infertility, Institute of Reproductive Medicine, Kolkata, IndiaDepartment of Bio-Medical Laboratory Science and Management, Vidyasagar University Midnapore, Midnapore, IndiaDivision of Molecular Medicine, Bose Institute, Calcutta Improvement Trust Scheme VIIM, Kolkata, IndiaBenzo(a)pyrene [B(a)P] is the toxic environmental Polycyclic Aromatic Hydrocarbon (PAH), that exerts male reproductive dysfunctions. In this study the molecular mechanism of B(a)P induced Leydig cell steroidogenic dysfunctions and its protective mechanism of action with a natural Aryl hydrocarbon receptor (AhR) antagonist and anti-oxidant, Resveratrol (Res) has been investigated. B(a)P exposure induced ROS mediated steroidogenic imbalance via activation of p38MAPK and repression of testosterone level as well as other steroidogenic enzymes like CYPIIA1, 3β-HSD, 17β-HSD expressions. B(a)P exposure decreased StAR protein expression along with increased DAX-1, a transcriptional repressor of StAR gene. Along with that B(a)P decreased the expression of SF-1 that acts as a transcriptional inducer of StAR gene expression. The study has established Resveratrol as a potential agent combating the deleterious effect of B(a)P on Leydig cell steroidogenesis. Resveratrol treatment resulted significant protection against B(a)P by scavenging ROS and modulating the transcriptional regulation of anti-oxidant enzymes. Furthermore, Resveratrol also prevented stress kinase like p38 MAPK activation and increased StAR protein expression through the reduction of DAX-1 expression. Moreover, the testosterone production was efficiently restored with Resveratrol treatment. ChIP assay also revealed that resveratrol improved SF-1expression which further increased the StAR gene expression. Resveratrol acted efficiently against B(a)P, through its anti-oxidative properties as well as inhibits p38MAPK and increased steroidogenesis and StAR expression through the modulation of SF-1 gene expression.https://www.frontiersin.org/article/10.3389/fendo.2019.00272/fullB(a)Pleydig cellROSStARp38 MAPKSF1 |
spellingShingle | Bhaswati Banerjee Supriya Chakraborty Pratip Chakraborty Debidas Ghosh Kuladip Jana Protective Effect of Resveratrol on Benzo(a)Pyrene Induced Dysfunctions of Steroidogenesis and Steroidogenic Acute Regulatory Gene Expression in Leydig Cells Frontiers in Endocrinology B(a)P leydig cell ROS StAR p38 MAPK SF1 |
title | Protective Effect of Resveratrol on Benzo(a)Pyrene Induced Dysfunctions of Steroidogenesis and Steroidogenic Acute Regulatory Gene Expression in Leydig Cells |
title_full | Protective Effect of Resveratrol on Benzo(a)Pyrene Induced Dysfunctions of Steroidogenesis and Steroidogenic Acute Regulatory Gene Expression in Leydig Cells |
title_fullStr | Protective Effect of Resveratrol on Benzo(a)Pyrene Induced Dysfunctions of Steroidogenesis and Steroidogenic Acute Regulatory Gene Expression in Leydig Cells |
title_full_unstemmed | Protective Effect of Resveratrol on Benzo(a)Pyrene Induced Dysfunctions of Steroidogenesis and Steroidogenic Acute Regulatory Gene Expression in Leydig Cells |
title_short | Protective Effect of Resveratrol on Benzo(a)Pyrene Induced Dysfunctions of Steroidogenesis and Steroidogenic Acute Regulatory Gene Expression in Leydig Cells |
title_sort | protective effect of resveratrol on benzo a pyrene induced dysfunctions of steroidogenesis and steroidogenic acute regulatory gene expression in leydig cells |
topic | B(a)P leydig cell ROS StAR p38 MAPK SF1 |
url | https://www.frontiersin.org/article/10.3389/fendo.2019.00272/full |
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