10−7 M genistein partially alleviates 10−7 M MEHP unfavorable effects in a new modified fetal rat testis culture system

Background: Recent studies revealed that some common endocrine-disrupting chemicals (EDCs) including phthalates and phytoestrogens may exhibit low-dose effects properties. However, how low dose of these EDCs and their mixture would affect fetal rat testis development still needs further investigatio...

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Main Authors: Tong-Dian Zhang, Yu-Bo Ma, Ming Gao, He-Cheng Li, Zi-Ming Wang, Tie Chong, Lian-Dong Zhang
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-08-01
Series:Frontiers in Cell and Developmental Biology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2022.987928/full
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author Tong-Dian Zhang
Tong-Dian Zhang
Yu-Bo Ma
Ming Gao
He-Cheng Li
Zi-Ming Wang
Tie Chong
Lian-Dong Zhang
author_facet Tong-Dian Zhang
Tong-Dian Zhang
Yu-Bo Ma
Ming Gao
He-Cheng Li
Zi-Ming Wang
Tie Chong
Lian-Dong Zhang
author_sort Tong-Dian Zhang
collection DOAJ
description Background: Recent studies revealed that some common endocrine-disrupting chemicals (EDCs) including phthalates and phytoestrogens may exhibit low-dose effects properties. However, how low dose of these EDCs and their mixture would affect fetal rat testis development still needs further investigation. Moreover, testis organ culture system also needs further modification to provide an effective tool for ex vivo EDCs study.Methods: We firstly modified the agarose organ culture system, in which fetal rat testes were cultured for 4 days (d1 to d4) on agarose gels held by Millicell inserts. Then we used the modified agarose culture system to study the combined effects of multiple EDCs exposure. 15.5 dpc fetal rat testes were isolated and treated with vehicle, MEHP (0.1 μmol/L), GEN (0.1 μmol/L) or MEHP (0.1 μmol/L) + GEN (0.1 μmol/L). Parameters concerning testicular cell development and function were evaluated, trying to gain insight into the early molecular events after multiple EDCs exposure.Results: The development of somatic, germ cells and seminiferous tubule in 15.5 dpc fetal rat testis was better sustained in the modified agarose culture system. Based on the modified system, we found that MEHP at 0.1 μmol/L induced alterations in gonocyte markers, antioxidative enzyme activity as well as transient reduction of testosterone production, accompanied by mitochondria swelling in gonocytes and Sertoli cells. No obvious morphological and histological alterations were observed in all treated groups. However, coadministration of genistein at 0.1 μmol/L partially alleviated MEHP-induced fetal testis damage ex vivo through enhancement of antioxidative action. MEHP at low dose still showed weak endocrine disrupting properties but did not exhibit typical low-dose effects.Conclusion: Our findings indicated that the modified agarose culture system could better mimic testicular microenvironment without obvious hypoxic cell damage. Furthermore, low dose of MEHP induced mild disruption to fetal testis development, cotreatment of genistein at low dose attenuated MEHP induced fetal testis injuries in part by balancing redox state, indicating that low dose of genistein may partially protect fetal testis from phthalates induced injury.
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spelling doaj.art-61ba5292430743b582988f10cf1d708c2022-12-22T02:18:12ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-08-011010.3389/fcell.2022.98792898792810−7 M genistein partially alleviates 10−7 M MEHP unfavorable effects in a new modified fetal rat testis culture systemTong-Dian Zhang0Tong-Dian Zhang1Yu-Bo Ma2Ming Gao3He-Cheng Li4Zi-Ming Wang5Tie Chong6Lian-Dong Zhang7Department of Urology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, ChinaDepartment of Andrology, Liaocheng People’s Hospital, Liaocheng, Shandong, ChinaDepartment of Urology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, ChinaDepartment of Nephrology, Xi’an No. 4 Hospital, Xi’an, Shaanxi, ChinaDepartment of Urology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, ChinaDepartment of Urology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, ChinaDepartment of Urology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, ChinaDepartment of Urology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, ChinaBackground: Recent studies revealed that some common endocrine-disrupting chemicals (EDCs) including phthalates and phytoestrogens may exhibit low-dose effects properties. However, how low dose of these EDCs and their mixture would affect fetal rat testis development still needs further investigation. Moreover, testis organ culture system also needs further modification to provide an effective tool for ex vivo EDCs study.Methods: We firstly modified the agarose organ culture system, in which fetal rat testes were cultured for 4 days (d1 to d4) on agarose gels held by Millicell inserts. Then we used the modified agarose culture system to study the combined effects of multiple EDCs exposure. 15.5 dpc fetal rat testes were isolated and treated with vehicle, MEHP (0.1 μmol/L), GEN (0.1 μmol/L) or MEHP (0.1 μmol/L) + GEN (0.1 μmol/L). Parameters concerning testicular cell development and function were evaluated, trying to gain insight into the early molecular events after multiple EDCs exposure.Results: The development of somatic, germ cells and seminiferous tubule in 15.5 dpc fetal rat testis was better sustained in the modified agarose culture system. Based on the modified system, we found that MEHP at 0.1 μmol/L induced alterations in gonocyte markers, antioxidative enzyme activity as well as transient reduction of testosterone production, accompanied by mitochondria swelling in gonocytes and Sertoli cells. No obvious morphological and histological alterations were observed in all treated groups. However, coadministration of genistein at 0.1 μmol/L partially alleviated MEHP-induced fetal testis damage ex vivo through enhancement of antioxidative action. MEHP at low dose still showed weak endocrine disrupting properties but did not exhibit typical low-dose effects.Conclusion: Our findings indicated that the modified agarose culture system could better mimic testicular microenvironment without obvious hypoxic cell damage. Furthermore, low dose of MEHP induced mild disruption to fetal testis development, cotreatment of genistein at low dose attenuated MEHP induced fetal testis injuries in part by balancing redox state, indicating that low dose of genistein may partially protect fetal testis from phthalates induced injury.https://www.frontiersin.org/articles/10.3389/fcell.2022.987928/fullmono-(2-ethylhexyl) phthalategenisteinfetal testisorgan cultureoxidative stress
spellingShingle Tong-Dian Zhang
Tong-Dian Zhang
Yu-Bo Ma
Ming Gao
He-Cheng Li
Zi-Ming Wang
Tie Chong
Lian-Dong Zhang
10−7 M genistein partially alleviates 10−7 M MEHP unfavorable effects in a new modified fetal rat testis culture system
Frontiers in Cell and Developmental Biology
mono-(2-ethylhexyl) phthalate
genistein
fetal testis
organ culture
oxidative stress
title 10−7 M genistein partially alleviates 10−7 M MEHP unfavorable effects in a new modified fetal rat testis culture system
title_full 10−7 M genistein partially alleviates 10−7 M MEHP unfavorable effects in a new modified fetal rat testis culture system
title_fullStr 10−7 M genistein partially alleviates 10−7 M MEHP unfavorable effects in a new modified fetal rat testis culture system
title_full_unstemmed 10−7 M genistein partially alleviates 10−7 M MEHP unfavorable effects in a new modified fetal rat testis culture system
title_short 10−7 M genistein partially alleviates 10−7 M MEHP unfavorable effects in a new modified fetal rat testis culture system
title_sort 10 7 m genistein partially alleviates 10 7 m mehp unfavorable effects in a new modified fetal rat testis culture system
topic mono-(2-ethylhexyl) phthalate
genistein
fetal testis
organ culture
oxidative stress
url https://www.frontiersin.org/articles/10.3389/fcell.2022.987928/full
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