Enhanced Inhibitory Effects of TBT Chloride on the Development of F1 Rats

Abstract

Neurotoxicity is one of the major effects of tributyltin (TBT). The effects on the next generation of F(1) rats exposed to TBT via the placenta and their dams' milk may be stronger than those on adults. Pregnant Wister rats were exposed to TBT at 0 and 125 ppm in their food. Half of the female F(1) rats in both groups were exposed to TBT at 125 ppm in their food from 9 to 15 weeks of age. Female F(1) rats were divided into the following groups: the control-control (CC) group, with no exposure; the TBT-control (TC) group, exposed to TBT via the placenta and their dams' milk; the control-TBT (CT) group, exposed to TBT via their food from 9 to 15 weeks of age; and the TBT-TBT (TT) group, exposed to TBT via the placenta, their dams' milk, and their food (n = 10/group). After administration, an open-field test and prepulse inhibition (PPI) test were performed at 15 weeks of age. The mean body weights of the TC and TT groups were significantly lower than that of the CC group from 9 to 15 weeks of age. The mean relative thymus weight of the TC and TT groups was significantly lower than that of the CC group. In the open-field test, a marked decrease in the total locomotion distance was observed in the TT group. The mean values in the TT and TC groups were significantly lower than that in the CC group. For the locomotion distance between 15 and 20 min, the mean values in the CT, TC, and TT groups were significantly lower than that in the CC group. The mean locomotor distance between 25 and 30 min in the TT group was significantly lower than that in the CC and TC groups. The mean values of instances of wall rearing in the TC, CT, and TT groups were significantly lower than that in the CC group. The mean value of face washing or body washing in the TT group was significantly lower than that in the CT group. There were no significant differences in indexes of the PPI test. Exposure to TBT via the placenta and their dams' milk inhibited the development of F(1) rats, which continued after weaning. Inhibition of the rats' activity induced by exposure to TBT via the placenta and their dams' milk and/or via their food was suggested. The effects were most evident in the TT group.

Changes in gene expression following long-term in vitro exposure of Macaca mulatta trophoblast stem cells to biologically relevant levels of endocrine disruptors

“…Organotin compounds induce progesterone synthesis in Jar cells [6]. TBT mediates intrauterine growth and post-natal growth restriction in rats [86], and inhibits aromatase activity in the placenta. Phthalates inhibit trophoblast invasion via PPARγ inhibition [7], disrupt placentation [8], and modify expression of lipid metabolism genes and fatty acid placental transport [9, 87].…”

Obesogenic Endocrine Disrupting Chemicals: Identifying Knowledge Gaps

“…Importantly, recent studies also documented transgenerational inheritance of obesogenic effects [40, 41]. Studies demonstrating a lack of obesogenic effect of TBT are scarce [43].…”

Childhood Obesity and Environmental Chemicals

“…Acute prenatal and postnatal exposure to TBT (sufficient to increase mortality) decreases postpubertal growth in mice (Table 3). 120–122 At lower doses, prenatal TBT exposure appears to have little to no impact on body mass while increasing adipose mass. Peripubertal exposure to TBT seems to increase the likelihood of increases in both body and fat mass.…”