Lack of effect on rat testicular organogenesis after in utero exposure to 3-monochloropropane-1,2-diol (3-MCPD).
3-Monochloropropane-1,2-diol (3-MCPD) is a food-born contaminant known to display toxic effects on male reproduction, producing infertility in rats and humans. Using the rat as a model, we investigated whether or not testicular organogenesis, which, in the rat species, occurs during the second half of gestation, was at particular risk regarding 3-MCPD toxicity. Pregnant rats were given daily doses of 5, 10 or 25 mg/kg BW of 3-MCPD from days 11.5-18.5 postcoitum (dpc). On 19.5 dpc, testes were removed from fetuses for histological examination and testosterone analysis. Eight genes were selected among the differentiation markers of testicular cell lineages, and their expression was studied by RT-PCR. The levels of 3-MCPD and its main metabolite, beta-chlorolactic acid, were assayed in fetal tissues and dam plasma. Our results show a statistically significant decrease in the mean body weight gain of pregnant rats treated with 10 and 25 mg/kg BW of 3-MCPD. Fetal testes exposed to 3-MCPD exhibited normal histology and produced testosterone at levels that were similar to controls. In addition, 3-MCPD did not alter gene expression in the fetal testes. This lack of effect occurred under conditions where 3-MCPD and beta-chlorolactic acid were found to readily cross the placental barrier and diffuse throughout the fetal tissues. Our findings indicate that 3-MCPD has minimal effect on rat testicular organogenesis.
Agence Française de Sécurité Sanitaire des Aliments, Unité de Toxicologie Génétique des Contaminants Alimentaires, la Haute Marche, 35133 Javené, Fougères, France. r.elramy@fougeres.afssa.fr
Rosy
R
El Ramy
Mostafa
M
Ould Elhkim
Martine
M
Poul
Maguelone G
MG
Forest
Patrick
P
Leduque
Brigitte
B
Le Magueresse-Battistoni
D000085:Acetates / Q000378:metabolism; D000818:Animals; D005260:Female; D005333:Fetus / Q000378:metabolism; D005865:Gestational Age; D005990:Glycerol / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000633:toxicity; D006801:Humans; D008297:Male; D008431:Maternal-Fetal Exchange; D038081:Organogenesis / Q000187:drug effects*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013737:Testis / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism; D000517:alpha-Chlorohydrin
D000085:Acetates; D013739:Testosterone; C006972:chloroacetic acid; D000517:alpha-Chlorohydrin; D005990:Glycerol