Tributyltin Impairs the Reproductive Cycle in Female Rats

Abstract

Triorganotins are environmental contaminants, commonly used in antifouling agents for boats, that bioaccumulate and thus are found in mammals and humans due to ingestion of contaminated seafood diets. The importance of triorganotins as environmental endocrine disruptors and consequent reproductive toxicity in different animal models is well known; however, the adverse effects on reproductive cycle are less well understood. The potential reproductive toxicity of tributyltin (TBT) on regular reproductive cycling of female rats was examined. Wistar female rats (12 wk old, weighing approximately 230 g) were divided into two groups: control (vehicle, ethanol 0.4%) and tributyltin (100 ng/kg/d, 7 d/wk, for 16 d by gavage). Tributyltin significantly decreased the cycle regularity (%), duration of the reproductive cycle, the proestrus and diestrus phases, and number of epithelial cell in proestrus phase. TBT also increased the duration of metestrus and the number of cornified cells in this phase. Ovary weight and serum 17β-estradiol levels decreased markedly, accompanied by a significant increase in progesterone levels. Histological analysis showed apoptotic cells in corpus luteum and granulosa cells layer, with cystic follicles after TBT exposure. Tributyltin also elevated number of atretic follicles and corpoa lutea. The micronucleus (MN) test, using Chinese hamster ovary cells, demonstrated a concentration-dependent mutagenic effect of TBT, and at 2.0 × 10(-2)ng/ml most of the cells were nonviable. The toxic potential of TBT over the reproductive cycle may be attributed to changes found in the ovarian weight, unbalanced levels of sexual female hormones, and number of ovarian follicles and corpora lutea.

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

“…The animals were weighed and randomly assigned to 3 treatment groups, and they were treated orally with either 0.5 mL distilled water (CON, n = 10), 600 mg day −1 homogenate of seafood with development of imposex and containing OTs (LNI, n = 10), or 600 mg day −1 homogenate of seafood without development of imposex and accumulation of OTs (LNN, n = 10). The oral route of exposure was chosen based on previous studies [3,24,[53][54][55][56]. Using OTs accumulated in seafood enabled us to compare our results with previous work on OTs and allowed us to compare the effects of OTs present in seafood, which has strongly toxic properties as one of its potential mechanisms [44,45].…”

“…LH and FSH were measured using an Elisa assay (#122043 DA-LH152 and #120037 DA-FSH151 EIA, Diagnostic Systems Laboratories, Saronno, Italy). Estrogen and progesterone were measured using a radioimmunoassay (Diagnostic Products Corporation, Los Angeles, CA, USA), as described by Podratz et al [53] and Rodrigues et al [55].…”

“…Smears were examined as stained preparations with hematoxylin and eosin (H & E), and observed with a light microscope to determine the stage of the estrous cycle [53]. The stage of the estrous cycle was classified as proestrus, estrus, or metestrus/diestrus based on observed ratios of cornified epithelial, nucleated epithelial and polymorphonuclear leukocytes as described in [62].…”

“…Therefore, our dose is estimated to be within the range of human exposure (in Brazil) to seafood containing OTs. The criterion for utilization of a 15 day treatment was based on a previously reported ovarian toxicity protocol [53,54]. The experimental procedures were in accordance with the Biomedical Research Guidelines for the Care and Use of Laboratory Animals [60], and the Ethics Committee for Animal Experiments of the Federal University of Espírito Santo (CEUA No.…”

“…Health risk assessments have largely been based on immunological studies in animal models or intake estimates of OTs in seafood sources [18,25,45,47,48]. In addition to those risks, mammalian studies have shown that OTs impair reproductive parameters, such as sexual hormone metabolism, estrogen receptor (ER) expression and its affinity by binder, gonadal development/function, uterine morphophysiology, pregnancy rate and others [23,24,[49][50][51][52][53]. Despite these discoveries using the rodent models and health risk assessments, few studies have directly explored the effect of OTs accumulated in seafood to mammalian reproductive function.…”