PARENT SESSION
REPRODUCTIVE TOXICOLOGY
Harborside C
7:30 AM-10:00 AM

(306) EXPOSURE OF DAMS TO TRIBUTYLTIN HAS GENDER-SPECIFIC EFFECTS ON GONADAL GENE EXPRESSION PROFILES OF THE FETUSES.

Adeeko, Adedayo¹, Li, Daming¹, Trasler, Jacquetta^1,2,3, Hales, Barbara¹, Robaire, Bernard^1,4, ¹ Dept Pharmacology and Therapeutics, Montreal, CA² Dept Pediatrics, Montreal, CA³ Dept Human Genetics, Montreal, CA⁴ Dept Obstetrics and Gynecology, Montreal, CA

ABSTRACT- Tributyltin (TBT) is used extensively in agriculture and industry and consequently is widely distributed in the environment. TBT is a known endocrine disruptor in some wildlife species and is transferred across the placenta. To evaluate how in utero exposure to TBT affects gonadogenesis in the offspring, timed pregnant Sprague Dawley rats were gavaged either with vehicle (olive oil) or TBT (20 mg/kg) from days 0-19 of gestation. On gestational day 20, five dams from each group were sacrificed, RNA was extracted from fetal testes and ovaries from littermates and labeled with 32P for gene expression profiling using Atlas Rat 1.2 arrays (Clontech); membranes were scanned and data analyzed (GeneSpring). A total of 261 genes were expressed in control testes; a slightly higher number, 287 genes, were expressed in the TBT-treated testes and 253 of these genes were expressed in both control and treated testes. Whereas only 4 genes were down regulated by at least 1.5-fold, 75 genes were up regulated by at least 1.5-fold as a result of in utero TBT exposure. The effects of TBT treatment on fetal ovarian gene expression were very different from those on fetal testes. The number of genes expressed in the control ovaries was 235 and in the TBT treated ovaries, 236; 222 of these genes were co-expressed. While 18 genes were down regulated by at least 1.5-fold, only 3 genes were increased by at least 1.5-fold as a result of in utero TBT exposure. Interestingly, transcripts for genes involved in mitochondrial functions were upregulated in the TBT-exposed testis but were not changed in the TBT-exposed ovary. While the ovarian expression of heat shock protein 90 was decreased by 1.5-fold, and transcripts for other stress-related genes tended to decrease, testicular expression of heat shock protein 90 was increased by 1.5-fold, and expression of stress-related genes tended to increase. Thus, in utero TBT exposure altered gene expression profiles in fetal gonads in a gender-specific manner. Funded by the Toxic Substances Research Initiative.

KEY WORDS: tributyltin, gene expression, fetal testis, fetal ovary