A new method for toxicity assays on human and mouse fetal testis R. Lambrot a,b,c, * , G. Livera a,b,c , H. Coffigny a,b,c , C. Pairault a,b,c , R. Frydman d , R. Habert a,b,c , V. Rouiller-Fabre a,b,c a CEA, DSV/DRR/SEGG/LDRG, 92265 Fontenay-aux-Roses, France b Université Paris-XII–Denis-Diderot, 92265 Fontenay-aux-Roses, France c Unit of Gametogenesis and Genotoxicity, Université Paris-XII, Inserm, U566, 92265 Fontenay-aux-Roses, France d Service de gynécologie–obstétrique, hôpital A.-Béclère, Clamart, France Received 13 January 2006; accepted 21 September 2006 Available online 16 October 2006 Abstract Exposure to environmental pollutants (EP) is associated with a wide range of toxic effects, in particular in testis development. Uranium is a potential pollutant of nuclear industry and over the last few years, its environmental concentrations have increased. In animals, the current procedures for evaluating the potential developmental toxicity of uranium are based on in vivo studies. These methods do not allow to know the direct effects on testicular cells and are obviously excluded for human experiments. Consequently, we have developed an in vitro culture system of the whole testis. In the present study we characterized and validated this organ culture system in both mouse fetal testes and human fetal testes recovered during the first trimester (6–12 weeks) of gestation. We compared the histological aspect, the number of germ cells and the testosterone production, before and after culture. Testicular architecture and intercellular communications were preserved, and organ culture appears as a powerful method for studying the early development of testicular gametogenesis and steroidogenesis in both species. Thus by using this method we will be able to investigate the effects of uranium on mouse and human developing testis. The mouse model will allow us to determine the dose range of interest without restriction of material. © 2006 Elsevier Masson SAS. All rights reserved. Keywords: Human; Mouse; Fetus; Testis development; Organ culture; Uranium 1. Introduction The adult testis has two fundamental functions: steroidogen- esis and gametogenesis. The steroidogenesis is characterized by the production of sexual steroids, such as testosterone which induces and maintains primary and secondary sexual characters. The gametogenesis consists in germ cell produc- tion. These two functions are initiated during fetal life and their onset is very important. Indeed, testosterone production induces male primary sexual characters, and the number of germ cells formed during fetal and neonatal life partly deter- mines the number of spermatozoids produced in adulthood and thus, the fecundity of the individual. In human, the chronology of testicular development has been studied. The genital ridge destined to develop into either a testis or an ovary appears at the fourth week of gestation (wk) and remains identical in males and females until the sixth week. From the seventh week on, testis and ovary can be morphologically distinguished from each other, the testis in particular contains germ cells, called gonocytes, and Sertoli cells, which are supporting cells, within testis cords [1,2]. Testis cords are surrounded by an interstitium which includes Leydig cells, producing testos- terone after the eighth week of gestation [3]. During the last years, attention has focused on the fetal tes- tis since many epidemiological, clinical and experimental clues have suggested that this organ is the target of endocrine dis- ruptors and genotoxic agents [4,5]. Exposure to environmental pollutants (EP), such as uranium, is associated with a wide range of toxic effects, both chemical and radiological, but the information concerning the toxicity on reproduction is scarce. Most reproductive effects of uranium are based on its chemical nature and properties, rather than on its radioactive action. In animals, the current procedures for evaluating the potential www.elsevier.com/locate/biochi Biochimie 88 (2006) 1831–1835 * Corresponding author. E-mail address: romain.lambrot@cea.fr (R. Lambrot). 0300-9084/$ - see front matter © 2006 Elsevier Masson SAS. All rights reserved. doi:10.1016/j.biochi.2006.09.022