Effect of mono-(2-ethylhexyl) phthalate on human and mouse fetal testis: In vitro and in vivo approaches

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• 作者：V. Muczynski^a ; ^b ; ^c ; J.P. Cravedi^d ; A. Lehraiki^a ; ^b ; ^c ; C. Levacher^a ; ^b ; ^c ; D. Moison^a ; ^b ; ^c ; C. Lecureuil^a ; ^b ; ^c ; S. Messiaen^a ; ^b ; ^c ; E. Perdu^d ; R. Frydman^e ; R. Habert^a ; ^b ; ^c ; V. Rouiller-Fabre^a ; ^b ; ^c ; ^{virginie.rouiller-fabre@cea.fr}
• 关键词：AMH ; anti-Mü ; llerian hormone ; DAB ; 3 ; 3&prime ; -diaminobenzidine ; DEHP ; di-(2-ethylhexyl) phthalate ; dpc ; days post coitum ; m/hFETA ; mouse/human FEtal Testis Assay ; HPLC ; High Pressure Liquid Chromatography ; LC&ndash ; MS/MS ; Liquid Chromatography&ndash ; T
• 刊名：Toxicology and Applied Pharmacology
• 出版年：2012
• 期刊代码：58_0041008x
• 类别：pha
• 出版时间：15 May, 2012
• 卷：261
• 期：1
• 页码：97-104
• 文件大小：775 K

摘要

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^鈭?#xA0;5 M 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 (7-12 weeks) of gestation and cultured in the presence or not of 10^鈭?#xA0;5 M 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^鈭?#xA0;5 M 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^鈭?#xA0;5 M exposure is sufficient to induce changes to the in vivo development of the human fetal male germ cells.