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5430513 
Journal Article 
Organotin compounds alter endocrine functions of human placental cells 
Nakanishi, T; Itoh, N; Utoguchi, N; Tanaka, K 
2003 
1 
Toxicologist
ISSN: 0731-9193 
72 
English 
Tributyltin (TBT) and triphenyltin (TPT) are known to induce an irreversible sexual abnormality of female neogastropod snails which is termed and quot;imposex and quot;. However, in humans, no studies have investigated disturbances in sexual development and reproductive function as a result of exposure to organotin compounds. The placenta plays a vital role in the maintenance of a pregnancy by delivering oxygen and nutrients from the maternal circulation to the fetus and by returning fetal metabolites to the mother. The placenta also has many crucial endocrine functions such as human chorionic gonadotropin (hCG) production and the aromatization of androgen substrates to estrogens. Thus these placental functions might be at high risk due to the developmental and reproductive toxicology of environmental contaminants which have endocrine-disrupting effects. In the present study, to extend knowledge on the sexual developmental and reproductive toxicity of organotin compounds in humans, we assessed the possible effect of organotin compounds on aromatase activity and hCG secretion by human choriocarcinoma cells. Both TBT and TPT increased levels of hCG secretion and aromatase activity in a dose- and time-dependent fashion following exposure to non-toxic concentration ranges. In addition, these compounds enhanced 8-bromo-cAMP-induced hCG secretion and aromatase activity in JAR cells. TBT caused dose-related increases in steady state mRNA levels of both hCG beta and CYP19 in JAR cells following exposure to non-toxic concentrations of TBT. Our studies suggest that TBT and TPT are potent stimulators of human placental hCG production and aromatase activity in vitro; and the placenta represents a potential target organ for these compounds, whose endocrine-disrupting effects might be the result of local changes in hCG and estrogen concentrations in pregnant women.