Perinatal exposure to low doses of tributyltin chloride advances puberty and affects patterns of estrous cyclicity in female mice

Abstract

Tributyltin (TBT), a proven endocrine-disrupting chemical, is well known to induce imposex in female gastropods. Herein we demonstrate the effects of low doses of tributyltin chloride (TBTCl) on the female offspring of KM mice. Pregnant mice were administered by gavage with 0, 1, 10, or 100 μg TBTCl/kg body weight/day from day 6 of pregnancy through the period of lactation. TBTCl dramatically advanced the age of onset of vaginal opening (VO) and first vaginal estrus, and reduced body weights at VO and first estrus. Furthermore, perinatal treatment with TBTCl significantly reduced the number of days between VO and first estrus. In addition, female offspring from dams exposed to 10 and 100 μg kg(-1) TBTCl exhibited altered patterns of estrous cyclicity in adulthood. In conclusion, perinatal exposure to low doses TBTCl result in early puberty and impaired estrous cyclicity in female mice, which suggest that TBTCl might act as an estrogen agonist or/and a disruptor on hypothalamic-pituitary function in the present study.

Accumulation of organotins in seafood leads to reproductive tract abnormalities in female rats

“…Thus, abnormal control of ovarian follicular development can lead to abnormal conditions such as premature ovarian failure or others ovarian dysfunctions, as observed for us. Moreover, in agreement with our findings, an increase in the number of atretic and cystic follicles was also observed in the ovaries of female pubertal rodents exposed to 6 mg of TPT and 100 g/kg of TBT [57,58]. Kishta et al [51] described a 44-46% reduction in ovarian germ cells in mice treated between 0-19 and 8-19 days of gestation at 20 and 10 mg/kg of TBT doses.…”

“…In addition, abnormal estrous cycles with a change in the length of the phases was observed in older rodents through changes in both ovarian and hypothalamic-pituitary hormones [79,80]. Si et al [58] Grote et al [24] Ema and Harazono [110] Costa et al [35] Santos et al [66] Ho and Leung [111] Kannan and Falandyzy [47] Kannan et al [48] Lo et al [112] This study OTs: organotins; TBT: tributyltin; TPT: triphenyltin; DBT: dibutyltin; ↑: increased; ↓: decreased; ↔: unchanged or similar to control; NR: not reported; NA: not applicable. In addition, ovarian follicular development was impaired in the LNI females with the presence of cystic follicles, and increased primary follicles, atretic follicles and CL, indicating an imbalance of sex hormones in these rat models.…”

“…In addition, we did not find a similar study using seafood containing OTs and evaluating reproductive parameters. For this reason, we needed to compare the adverse effect found in our model with other toxicological studies that used pure OTs, such as TBT or triphenyltin (TPT) [3,24,57,58]. Furthermore, we evaluated the level of tin present in the seafood used in our model by an inductively coupled plasma mass spectrometer (ICP-MS).…”

Triorganotin compounds - ligands for “rexinoid” inducible transcription factors: Biological effects

“…In mammals, tributyltin also provokes fetal toxicity. Perinatal exposure to low doses tributyltin chloride result in early puberty and impaired estrous cyclicity in female mice, which suggest that it might act as an estrogen agonist or/and a disruptor on hypothalamic-pituitary function (Si et al, 2012).…”

Environmental Factors and Puberty Onset: An Update

“…Similarly, tributylin chloride (TBTCl) exposure during gestational period significantly accelerated the age at vaginal opening as compared to control group. TBTCl advanced the age of onset of VO in this study, indicative of an estrogenic effect (Jiliang et al, 2012). In another cohort study, data from female participants 12-16 years of age for phthalate and parapens in (NHANES) were analyzed.…”