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Evidence for Sex-specific Effects of TCDD on Male and Female Progeny Exposed in Utero

Le Magueress-Battistoni, B*; Odet, F*; Guigon, C; Vérot, A*; Guyot, R*; Ramy, Re*; Desses, P; Lazar, V; Coudouel, N; Bleux, C; Forest, M*; Leduque, P*; Magre, S

ISEE/ISEA 2006 Conference Abstracts Supplement: Session Abstracts: Abstracts

*INSERM U418, UMR INRA, Lyon, France; †UMR CNRS 7079, Paris, France; and ‡Institut Gustave Roussy, Villejuif, France


Reproductive and developmental disorders are the most sensitive toxic effects caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The present study aimed at examining specific endpoints in males and females exposed in utero. To that purpose, pregnant rats were given one oral dose of TCDD (0.2 μg/kg) on gestational day 15. Preliminary experiments established that the dose 1 μg/kg induced maternal and fetal toxicity. TCDD 0.2 μg/kg caused no changes in growth curve, testis weight, or testicular histology. Furthermore, intratesticular levels of testosterone, 17-beta estradiol or DHT measured at 3, 20, 32, 45, and 90 days postnatal (dpn) were normal. However, we noticed an increased germ cell apoptosis during the juvenile period and a 30% decrease in sperm numbers at 67 and 90 dpn. We next used a microarray gene expression profiling (Agilent technology) to identify genes with altered transcript levels at specific time-points during testicular development (3 and 32 dpn). Although data have yet to be validated using a quantitative RT-PCR procedure, it is worth to note that most genes identified encode proteins involved in cell cycle and apoptosis. In female progeny, TCDD caused no changes in the onset of puberty or in fertility at the beginning of the reproductive life. However, we noticed an increase in ovarian weight during the prepubertal period. We also observed that the growth of follicles in the prepubertal ovaries was accelerated. This was demonstrated using in situ hybridization and specific markers of follicular maturation. Furthermore, preliminary results obtained from microarray gene expression profiling and quantitative RT-PCR allowed the identification of endocrine-related genes induced by TCDD. Our data are in line with the hypothesis of an alteration of the endocrine function in the prepubertal ovary. Collectively, our data suggest that an embryonic in utero exposure to an endocrine disruptor (TCDD) may alter the endocrine environment of the germinal lineage during the prepubertal period, in the female progeny. In the male progeny, the TCDD treatment would result in an abnormal germ cell differentiation in the juvenile period with a subsequent alteration of the adult spermatogenic capacity.

© 2006 Lippincott Williams & Wilkins, Inc.