Chronic Dietary Exposure to a Low-Dose Mixture of Genistein and Vinclozolin Modifies the Reproductive Axis, Testis Transcriptome, and Fertility.

Autor: Eustache, Florence1, Mondon, Françoise2,3,4, Canivenc-Lavier, Marie Chantal5, Lesaffre, Corinne2,3,4, Fulla, Yvonne6, Berges, Raymond5, Cravedi, Jean Pierre7, Vaiman, Daniel2,3,4,8, Auger, Jacques1 jacques.auger@cch.aphp.fr
Předmět:
Zdroj: Environmental Health Perspectives. Aug2009, Vol. 117 Issue 8, p1272-1279. 8p. 3 Charts, 4 Graphs.
Abstrakt: Background: The reproductive consequences and mechanisms of action of chronic exposure to low-dose endocrine disruptors are poorly understood. Objective: We assessed the effects of a continuous, low-dose exposure to a phytoestrogen (genistein) and/or an antiandrogenic food contaminant (vinclozolin) on the male reproductive tract and fertility. Methods: Male rats were exposed by gavage to genistein and vinclozolin from conception to adulthood, alone or in combination, at low doses (1 mg/kg/day) or higher doses (10 and 30 mg/kg/day). We studied a number of standard reproductive toxicology end points and also assessed testicularmRNA expression profiles using long-oligonucleotide microarrays. Results: The low-dose mixture and high-dose vinclozolin produced the most significant alterations in adults: decreased sperm counts, reduced sperm motion parameters, decreased litter sizes, and increased postimplantation loss. Testicular mRNA expression profiles for these exposure conditions were strongly correlated. Functional clustering indicated that many of the genes induced belong to the "neuroactive ligand-receptor interactions" family encompassing several hormonally related actors (e.g., follicle-stimulating hormone and its receptor). All exposure conditions decreased the levels of mRNAs involved in ribosome function, indicating probable decreased protein production. Conclusions: Our study shows that chronic exposure to a mixture of a dose of a phytoestrogenequivalent to that in the human diet and a low dose—albeit not environmental—of a common antiandrogenic food contaminant may seriously affect the male reproductive tract and fertility. [ABSTRACT FROM AUTHOR]
Databáze: GreenFILE