Effects of neonatal exposure to tributyltin on the rat brain myelination.

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Tributyltin (TBT) is recognized as an endocrine-disrupting chemical, because of suppressing the aromatase for conversion of androgen to estrogen. The purpose of this study was to evaluate the effect of TBT on development of rat neuronal tissues.A: Prenatal exposure to TBT(1) Pregnant rats were exposed TBT on days 7 or 14 of pregnancy. The offspring brains were collected on the 21st day after birth. Steroid contents, P450 activity in microsome fractions, and the activities of oligodendrocyte enzyme CNP (2', 3'-cyclic nucleotide 3'-phosphodiesterase) in the TBT exposed rats were not significantly different from those in the control rats. Results showed that prenatal exposure to TBT did not affect the brain development of offspring. The fetuses are probably defended from TBT by the placenta.B: Neonatal exposure to TBT(1) Neonatal rats were exposed TBT on the day of birth. Brains of offspring were collected on 21, 35, and 49 days of age. The CNP activities of myelin in all neonatal TBT exposed groups were significantly decreased compared with those of the control groups even in the relatively low level exposure. Western blot analysis of CNP showed the similar results as enzyme activities at each developmental stage. (2) The mRNA levels of major brain myelin proteins of TBT-exposed rats were selectively affected compared with the levels of control rats. (3) The mRNA levels of glycolipid synthesis glycosyltransferases in the brains of TBT-exposed rats were almost same as the levels of control rats. However, the levels of GlcCer synthase and CSE synthase (sulfatide synthase) of TBT-exposed rat brain at 7 weeks of age were remarkably decreased compared with the levels of control rats. (4) TLC profiles of sphingoglycolipids and phospholipids in the brains of TBT-exposed and control rats were examined. (289 words)