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

(304) EXPOSURE IN UTERO TO TRIBUTYLTIN CHLORIDE REDUCED VENTRAL PROSTATE WEIGHT AND ALTERED GENE EXPRESSION IN THE PROGENY.

Robaire, Bernard^1,2, Luu, Trang¹, Adeeko, Adedayo¹, Li, Daming¹, Hales, Barbara¹, ¹ Dept of Pharmacology and Therapeutics, Montreal, CA² Dept of Obstetrics and Gynecology, Montreal, CA

ABSTRACT- Tributyltin (TBT) is ubiquitous in the environment. It is used in the ship construction industry, as a fungicide in agriculture, and for the stabilization of PVC pipes. TBT is an endocrine disruptor and is transferred to the conceptus through the placenta. Exposure of humans to TBT, especially during pregnancy, is a public health concern. To evaluate if in utero exposure to TBT has long term consequences on an androgen sensitive organ, the ventral prostate, timed pregnant Sprague Dawley rats were gavaged either with vehicle (olive oil) or TBT chloride (10 mg/kg body weight) throughout pregnancy and allowed to deliver. Neither the weight of the dams nor that of their offspring was affected by the treatment. However, ventral prostate weights in adult (90 days) male offspring were dramatically reduced (control: 0.60±0.04g; TBT: 0.37±0.04g). To determine whether this weight reduction was associated with selective modification of gene expression, we investigated the gene expression profiles in ventral prostates from adult progeny exposed in utero to vehicle (n=4) or TBT (n=4) using the Atlas Rat 1.2 arrays (Clontech); membranes were scanned and data analyzed (GeneSpring). While 237 genes were expressed in control ventral prostates, only 194 genes were detected in prostates from rats exposed to TBT in utero; 47 genes were expressed exclusively in the control ventral prostate, but only 3 genes were expressed exclusively in those exposed to TBT. A total of 32 genes were down regulated by at least 1.5-fold following in utero exposure to TBT; no genes were up regulated as a result of exposure to TBT. The down regulated genes included two cytoskeletal proteins, five protease-related genes, and six nucleases or related to nucleotide (GTP or ATP) binding proteins. These data demonstrate that exposure of dams to TBT, at apparently non-toxic doses, resulted in dramatic effects on both tissue weight and gene expression in the ventral prostate of adult progeny. Funded by the Toxic Substances Research Initiative.

KEY WORDS: tributyltin, ventral prostate, gene expression profile, in utero exposure