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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Veröffentlicht in:Toxicology and applied pharmacology 2012-05, Vol.261 (1), p.97-104
Hauptverfasser: Muczynski, V., Cravedi, J.P., Lehraiki, A., Levacher, C., Moison, D., Lecureuil, C., Messiaen, S., Perdu, E., Frydman, R., Habert, R., Rouiller-Fabre, V.
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container_issue 1
container_start_page 97
container_title Toxicology and applied pharmacology
container_volume 261
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
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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 &amp; 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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