Effect of mono-(2-ethylhexyl) phthalate on human and mouse fetal testis: In vitro and in vivo approaches
The present study was conducted to determine whether exposure to the mono-(2-ethylhexyl) phthalate (MEHP) represents a genuine threat to male human reproductive function. To this aim, we investigated the effects on human male fetal germ cells of a 10−5M exposure. This dose is slightly above the mean...
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creator | Muczynski, V. Cravedi, J.P. Lehraiki, A. Levacher, C. Moison, D. Lecureuil, C. Messiaen, S. Perdu, E. Frydman, R. Habert, R. Rouiller-Fabre, V. |
description | The present study was conducted to determine whether exposure to the mono-(2-ethylhexyl) phthalate (MEHP) represents a genuine threat to male human reproductive function. To this aim, we investigated the effects on human male fetal germ cells of a 10−5M exposure. This dose is slightly above the mean concentrations found in human fetal cord blood samples by biomonitoring studies. The in vitro experimental approach was further validated for phthalate toxicity assessment by comparing the effects of in vitro and in vivo exposure in mouse testes.
Human fetal testes were recovered during the first trimester (7–12weeks) of gestation and cultured in the presence or not of 10−5M MEHP for three days. Apoptosis was quantified by measuring the percentage of Caspase-3 positive germ cells. The concentration of phthalate reaching the fetal gonads was determined by radioactivity measurements, after incubations with 14C-MEHP.
A 10−5M exposure significantly increased the rate of apoptosis in human male fetal germ cells. The intratesticular MEHP concentration measured corresponded to the concentration added in vitro to the culture medium. Furthermore, a comparable effect on germ cell apoptosis in mouse fetal testes was induced both in vitro and in vivo.
This study suggests that this 10−5M exposure is sufficient to induce changes to the in vivo development of the human fetal male germ cells.
► 10−5M of MEHP impairs germ cell development in the human fetal testis. ► Organotypic culture is a suitable approach to investigate phthalate effects in human. ► MEHP is not metabolized in the human fetal testis. ► In mice, MEHP triggers similar effects both in vivo and in vitro. |
doi_str_mv | 10.1016/j.taap.2012.03.016 |
format | Article |
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Human fetal testes were recovered during the first trimester (7–12weeks) of gestation and cultured in the presence or not of 10−5M MEHP for three days. Apoptosis was quantified by measuring the percentage of Caspase-3 positive germ cells. The concentration of phthalate reaching the fetal gonads was determined by radioactivity measurements, after incubations with 14C-MEHP.
A 10−5M exposure significantly increased the rate of apoptosis in human male fetal germ cells. The intratesticular MEHP concentration measured corresponded to the concentration added in vitro to the culture medium. Furthermore, a comparable effect on germ cell apoptosis in mouse fetal testes was induced both in vitro and in vivo.
This study suggests that this 10−5M exposure is sufficient to induce changes to the in vivo development of the human fetal male germ cells.
► 10−5M of MEHP impairs germ cell development in the human fetal testis. ► Organotypic culture is a suitable approach to investigate phthalate effects in human. ► MEHP is not metabolized in the human fetal testis. ► In mice, MEHP triggers similar effects both in vivo and in vitro.</description><identifier>ISSN: 0041-008X</identifier><identifier>EISSN: 1096-0333</identifier><identifier>DOI: 10.1016/j.taap.2012.03.016</identifier><identifier>PMID: 22484159</identifier><identifier>CODEN: TXAPA9</identifier><language>eng</language><publisher>Amsterdam: Elsevier Inc</publisher><subject>60 APPLIED LIFE SCIENCES ; Animals ; APOPTOSIS ; Apoptosis - drug effects ; Biological and medical sciences ; BLOOD ; CARBON 14 ; Carbon Radioisotopes ; Caspase 3 - metabolism ; CONCENTRATION RATIO ; CULTURE MEDIA ; Diethylhexyl Phthalate - analogs & derivatives ; Diethylhexyl Phthalate - pharmacokinetics ; Diethylhexyl Phthalate - toxicity ; Dose-Response Relationship, Drug ; Fetus ; Germ cell ; GERM CELLS ; Germ Cells - drug effects ; Germ Cells - metabolism ; GOATS ; HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY ; HORMONES ; Human ; Humans ; IN VITRO ; In Vitro Techniques ; IN VIVO ; Life Sciences ; Male ; MASS SPECTROSCOPY ; Medical sciences ; MICE ; Mice, Inbred C57BL ; PHTHALATES ; RADIOACTIVITY ; Reproductive Biology ; RETENTION ; Sexual reproduction ; Species Specificity ; Testis ; Testis - drug effects ; Testis - embryology ; TOXICITY ; Toxicology</subject><ispartof>Toxicology and applied pharmacology, 2012-05, Vol.261 (1), p.97-104</ispartof><rights>2012 Elsevier Inc.</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2012 Elsevier Inc. All rights reserved.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c591t-b0914914373add196d01a278e14904c400cb75e979e833569f72e74dcac0cf203</citedby><cites>FETCH-LOGICAL-c591t-b0914914373add196d01a278e14904c400cb75e979e833569f72e74dcac0cf203</cites><orcidid>0000-0002-7339-9185 ; 0000-0002-6045-0324 ; 0000-0002-5503-5337</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.taap.2012.03.016$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=25985604$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22484159$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-00776675$$DView record in HAL$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/22215319$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Muczynski, V.</creatorcontrib><creatorcontrib>Cravedi, J.P.</creatorcontrib><creatorcontrib>Lehraiki, A.</creatorcontrib><creatorcontrib>Levacher, C.</creatorcontrib><creatorcontrib>Moison, D.</creatorcontrib><creatorcontrib>Lecureuil, C.</creatorcontrib><creatorcontrib>Messiaen, S.</creatorcontrib><creatorcontrib>Perdu, E.</creatorcontrib><creatorcontrib>Frydman, R.</creatorcontrib><creatorcontrib>Habert, R.</creatorcontrib><creatorcontrib>Rouiller-Fabre, V.</creatorcontrib><title>Effect of mono-(2-ethylhexyl) phthalate on human and mouse fetal testis: In vitro and in vivo approaches</title><title>Toxicology and applied pharmacology</title><addtitle>Toxicol Appl Pharmacol</addtitle><description>The present study was conducted to determine whether exposure to the mono-(2-ethylhexyl) phthalate (MEHP) represents a genuine threat to male human reproductive function. To this aim, we investigated the effects on human male fetal germ cells of a 10−5M exposure. This dose is slightly above the mean concentrations found in human fetal cord blood samples by biomonitoring studies. The in vitro experimental approach was further validated for phthalate toxicity assessment by comparing the effects of in vitro and in vivo exposure in mouse testes.
Human fetal testes were recovered during the first trimester (7–12weeks) of gestation and cultured in the presence or not of 10−5M MEHP for three days. Apoptosis was quantified by measuring the percentage of Caspase-3 positive germ cells. The concentration of phthalate reaching the fetal gonads was determined by radioactivity measurements, after incubations with 14C-MEHP.
A 10−5M exposure significantly increased the rate of apoptosis in human male fetal germ cells. The intratesticular MEHP concentration measured corresponded to the concentration added in vitro to the culture medium. Furthermore, a comparable effect on germ cell apoptosis in mouse fetal testes was induced both in vitro and in vivo.
This study suggests that this 10−5M exposure is sufficient to induce changes to the in vivo development of the human fetal male germ cells.
► 10−5M of MEHP impairs germ cell development in the human fetal testis. ► Organotypic culture is a suitable approach to investigate phthalate effects in human. ► MEHP is not metabolized in the human fetal testis. ► In mice, MEHP triggers similar effects both in vivo and in vitro.</description><subject>60 APPLIED LIFE SCIENCES</subject><subject>Animals</subject><subject>APOPTOSIS</subject><subject>Apoptosis - drug effects</subject><subject>Biological and medical sciences</subject><subject>BLOOD</subject><subject>CARBON 14</subject><subject>Carbon Radioisotopes</subject><subject>Caspase 3 - metabolism</subject><subject>CONCENTRATION RATIO</subject><subject>CULTURE MEDIA</subject><subject>Diethylhexyl Phthalate - analogs & derivatives</subject><subject>Diethylhexyl Phthalate - pharmacokinetics</subject><subject>Diethylhexyl Phthalate - toxicity</subject><subject>Dose-Response Relationship, Drug</subject><subject>Fetus</subject><subject>Germ cell</subject><subject>GERM CELLS</subject><subject>Germ Cells - drug effects</subject><subject>Germ Cells - metabolism</subject><subject>GOATS</subject><subject>HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY</subject><subject>HORMONES</subject><subject>Human</subject><subject>Humans</subject><subject>IN VITRO</subject><subject>In Vitro Techniques</subject><subject>IN VIVO</subject><subject>Life Sciences</subject><subject>Male</subject><subject>MASS SPECTROSCOPY</subject><subject>Medical sciences</subject><subject>MICE</subject><subject>Mice, Inbred C57BL</subject><subject>PHTHALATES</subject><subject>RADIOACTIVITY</subject><subject>Reproductive Biology</subject><subject>RETENTION</subject><subject>Sexual reproduction</subject><subject>Species Specificity</subject><subject>Testis</subject><subject>Testis - drug effects</subject><subject>Testis - embryology</subject><subject>TOXICITY</subject><subject>Toxicology</subject><issn>0041-008X</issn><issn>1096-0333</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kV-L1DAUxYso7rj6BXyQggi7D603f9o0iy_LsroLA74o-BYy6S3N0Ca1yQzOtze14_omBJIcfvdyzz1Z9pZASYDUH_dl1HoqKRBaAiuT9CzbEJB1AYyx59kGgJMCoPlxkb0KYQ8AknPyMruglDecVHKT9fddhybmvstH73xxRQuM_Wno8ddpuM6nPvZ60BFz7_L-MGqXa9cm9BAw7zDqIY8Yog03-aPLjzbO_g9gl88xvadp9tr0GF5nLzo9BHxzvi-z75_vv909FNuvXx7vbreFqSSJxQ4k4ekwwXTbElm3QDQVDSYVuOEAZicqlEJiw1hVy05QFLw12oDpKLDL7P3a16exVDA2oumNdy65VJRSUjEiE3W9UsmdmmY76vmkvLbq4XarFg1AiLoW1ZEk9mplk5Wfh-RWjTYYHAbtMO1BpSyEFIw2C0pX1Mw-hBm7p94EFq5We7VkppbMFDCVpFT07tz_sBuxfSr5G1ICPpwBHYweulk7Y8M_rpJNVQNP3KeVw7Tfo8V5sY_OYGvnxX3r7f_m-A2wq7Hx</recordid><startdate>20120515</startdate><enddate>20120515</enddate><creator>Muczynski, V.</creator><creator>Cravedi, J.P.</creator><creator>Lehraiki, A.</creator><creator>Levacher, C.</creator><creator>Moison, D.</creator><creator>Lecureuil, C.</creator><creator>Messiaen, S.</creator><creator>Perdu, E.</creator><creator>Frydman, R.</creator><creator>Habert, R.</creator><creator>Rouiller-Fabre, V.</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7U7</scope><scope>C1K</scope><scope>1XC</scope><scope>VOOES</scope><scope>OTOTI</scope><orcidid>https://orcid.org/0000-0002-7339-9185</orcidid><orcidid>https://orcid.org/0000-0002-6045-0324</orcidid><orcidid>https://orcid.org/0000-0002-5503-5337</orcidid></search><sort><creationdate>20120515</creationdate><title>Effect of mono-(2-ethylhexyl) phthalate on human and mouse fetal testis: In vitro and in vivo approaches</title><author>Muczynski, V. ; Cravedi, J.P. ; Lehraiki, A. ; Levacher, C. ; Moison, D. ; Lecureuil, C. ; Messiaen, S. ; Perdu, E. ; Frydman, R. ; Habert, R. ; Rouiller-Fabre, V.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c591t-b0914914373add196d01a278e14904c400cb75e979e833569f72e74dcac0cf203</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>60 APPLIED LIFE SCIENCES</topic><topic>Animals</topic><topic>APOPTOSIS</topic><topic>Apoptosis - drug effects</topic><topic>Biological and medical sciences</topic><topic>BLOOD</topic><topic>CARBON 14</topic><topic>Carbon Radioisotopes</topic><topic>Caspase 3 - metabolism</topic><topic>CONCENTRATION RATIO</topic><topic>CULTURE MEDIA</topic><topic>Diethylhexyl Phthalate - analogs & derivatives</topic><topic>Diethylhexyl Phthalate - pharmacokinetics</topic><topic>Diethylhexyl Phthalate - toxicity</topic><topic>Dose-Response Relationship, Drug</topic><topic>Fetus</topic><topic>Germ cell</topic><topic>GERM CELLS</topic><topic>Germ Cells - drug effects</topic><topic>Germ Cells - metabolism</topic><topic>GOATS</topic><topic>HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY</topic><topic>HORMONES</topic><topic>Human</topic><topic>Humans</topic><topic>IN VITRO</topic><topic>In Vitro Techniques</topic><topic>IN VIVO</topic><topic>Life Sciences</topic><topic>Male</topic><topic>MASS SPECTROSCOPY</topic><topic>Medical sciences</topic><topic>MICE</topic><topic>Mice, Inbred C57BL</topic><topic>PHTHALATES</topic><topic>RADIOACTIVITY</topic><topic>Reproductive Biology</topic><topic>RETENTION</topic><topic>Sexual reproduction</topic><topic>Species Specificity</topic><topic>Testis</topic><topic>Testis - drug effects</topic><topic>Testis - embryology</topic><topic>TOXICITY</topic><topic>Toxicology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Muczynski, V.</creatorcontrib><creatorcontrib>Cravedi, J.P.</creatorcontrib><creatorcontrib>Lehraiki, A.</creatorcontrib><creatorcontrib>Levacher, C.</creatorcontrib><creatorcontrib>Moison, D.</creatorcontrib><creatorcontrib>Lecureuil, C.</creatorcontrib><creatorcontrib>Messiaen, S.</creatorcontrib><creatorcontrib>Perdu, E.</creatorcontrib><creatorcontrib>Frydman, R.</creatorcontrib><creatorcontrib>Habert, R.</creatorcontrib><creatorcontrib>Rouiller-Fabre, V.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><collection>OSTI.GOV</collection><jtitle>Toxicology and applied pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Muczynski, V.</au><au>Cravedi, J.P.</au><au>Lehraiki, A.</au><au>Levacher, C.</au><au>Moison, D.</au><au>Lecureuil, C.</au><au>Messiaen, S.</au><au>Perdu, E.</au><au>Frydman, R.</au><au>Habert, R.</au><au>Rouiller-Fabre, V.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effect of mono-(2-ethylhexyl) phthalate on human and mouse fetal testis: In vitro and in vivo approaches</atitle><jtitle>Toxicology and applied pharmacology</jtitle><addtitle>Toxicol Appl Pharmacol</addtitle><date>2012-05-15</date><risdate>2012</risdate><volume>261</volume><issue>1</issue><spage>97</spage><epage>104</epage><pages>97-104</pages><issn>0041-008X</issn><eissn>1096-0333</eissn><coden>TXAPA9</coden><abstract>The present study was conducted to determine whether exposure to the mono-(2-ethylhexyl) phthalate (MEHP) represents a genuine threat to male human reproductive function. To this aim, we investigated the effects on human male fetal germ cells of a 10−5M exposure. This dose is slightly above the mean concentrations found in human fetal cord blood samples by biomonitoring studies. The in vitro experimental approach was further validated for phthalate toxicity assessment by comparing the effects of in vitro and in vivo exposure in mouse testes.
Human fetal testes were recovered during the first trimester (7–12weeks) of gestation and cultured in the presence or not of 10−5M MEHP for three days. Apoptosis was quantified by measuring the percentage of Caspase-3 positive germ cells. The concentration of phthalate reaching the fetal gonads was determined by radioactivity measurements, after incubations with 14C-MEHP.
A 10−5M exposure significantly increased the rate of apoptosis in human male fetal germ cells. The intratesticular MEHP concentration measured corresponded to the concentration added in vitro to the culture medium. Furthermore, a comparable effect on germ cell apoptosis in mouse fetal testes was induced both in vitro and in vivo.
This study suggests that this 10−5M exposure is sufficient to induce changes to the in vivo development of the human fetal male germ cells.
► 10−5M of MEHP impairs germ cell development in the human fetal testis. ► Organotypic culture is a suitable approach to investigate phthalate effects in human. ► MEHP is not metabolized in the human fetal testis. ► In mice, MEHP triggers similar effects both in vivo and in vitro.</abstract><cop>Amsterdam</cop><pub>Elsevier Inc</pub><pmid>22484159</pmid><doi>10.1016/j.taap.2012.03.016</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-7339-9185</orcidid><orcidid>https://orcid.org/0000-0002-6045-0324</orcidid><orcidid>https://orcid.org/0000-0002-5503-5337</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | 60 APPLIED LIFE SCIENCES Animals APOPTOSIS Apoptosis - drug effects Biological and medical sciences BLOOD CARBON 14 Carbon Radioisotopes Caspase 3 - metabolism CONCENTRATION RATIO CULTURE MEDIA Diethylhexyl Phthalate - analogs & derivatives Diethylhexyl Phthalate - pharmacokinetics Diethylhexyl Phthalate - toxicity Dose-Response Relationship, Drug Fetus Germ cell GERM CELLS Germ Cells - drug effects Germ Cells - metabolism GOATS HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY HORMONES Human Humans IN VITRO In Vitro Techniques IN VIVO Life Sciences Male MASS SPECTROSCOPY Medical sciences MICE Mice, Inbred C57BL PHTHALATES RADIOACTIVITY Reproductive Biology RETENTION Sexual reproduction Species Specificity Testis Testis - drug effects Testis - embryology TOXICITY Toxicology |
title | Effect of mono-(2-ethylhexyl) phthalate on human and mouse fetal testis: In vitro and in vivo approaches |
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