title: Placental transfer of a hydroxylated polychlorinated biphenyl and effects on fetal and maternal thyroid hormone homeostasis in the rat.
abstract: Earlier studies at our laboratory indicated that several hydroxylated polychlorinated biphenyls (OH-PCBs) detected in human blood could specifically inhibit thyroxine (T(4)) transport by competitive binding to the thyroid hormone transport protein transthyretin (TTR) in vitro. In the present study we investigated the effects of prenatal exposure to 5 mg/kg body weight of [14C]-labeled or unlabeled 4-OH-2,3,3',4',5-pentachlorobiphenyl (4-OH-CB107), one of the major metabolites of PCBs detected in human blood, from gestation days (GD) 10 to 16 on thyroid hormone status and metabolism in pregnant rats and their fetuses at GD 17 and GD 20. 4-OH-CB107 is a metabolite of both 2,3,3',4,4'-pentachlorobiphenyl (CB-105) and 2,3',4,4',5-pentachlorobiphenyl (CB-118). We were able to show the accumulation of 4-OH-CB107 in the fetal compartment. The fetal/maternal ratios at GD 20 in liver, cerebellum, and plasma were 11.0, 2.6, and 1.2, respectively. The 14C-4-OH-CB107-derived radioactivity in plasma was bound to TTR in both dams and fetuses. Fetal plasma TT(4) and FT(4) levels were significantly decreased at GD 17 and GD 20 (89% and 41% respectively at GD 20). Fetal thyroid stimulating hormone levels were increased by 124% at GD 20. The T(4) concentrations in fetal forebrain homogenates at GD20 were reduced by 35%, but no effects could be detected on brain T(3) concentrations. The deiodination of T(4) to T(3) was significantly increased in fetal forebrain homogenates at GD 17, and unaltered at GD 20. In addition, no alterations were observed in maternal and fetal hepatic T(4)-UDP-glucuronosyltransferase activity, type I deiodinase activity, and EROD activity. In conclusion, exposure of pregnant rats to 4-OH-CB107 results in the distribution of the compound in the maternal and fetal compartment, which is probably caused by the binding of the PCB metabolite to TTR. Consequently, TT(4) levels in fetal plasma and brain samples were reduced. Despite reductions in fetal brain T(4) levels, the active hormone (T(3)) in fetal brains remained unaffected.
authors.affiliation: Toxicology Group, Wageningen University and Research Center, Tuinlaan 5, 6703 HE Wageningen, The Netherlands. ilonka.meerts@notox.nl
authors.forename: Ilonka A T M
authors.initials: IA
authors.lastname: Meerts
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Assink
authors.forename: Peter H
authors.initials: PH
authors.lastname: Cenijn
authors.forename: Johannes H J
authors.initials: JH
authors.lastname: Van Den Berg
authors.forename: Bert M
authors.initials: BM
authors.lastname: Weijers
authors.forename: Ake
authors.initials: A
authors.lastname: Bergman
authors.forename: Jan H
authors.initials: JH
authors.lastname: Koeman
authors.forename: Abraham
authors.initials: A
authors.lastname: Brouwer
mesh_terms: D000818:Animals; D001921:Brain / Q000196:embryology / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000187:drug effects* / Q000378:metabolism; D006706:Homeostasis; D008297:Male; D018811:Maternal Exposure; D008431:Maternal-Fetal Exchange; D011078:Polychlorinated Biphenyls / Q000493:pharmacokinetics*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D013963:Thyroid Hormones / Q000378:metabolism*; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000378:metabolism; D014018:Tissue Distribution; D014284:Triiodothyronine / Q000378:metabolism
chemical_list: C111120:2,3,3',4',5-pentachloro-4-hydroxybiphenyl; D013963:Thyroid Hormones; D014284:Triiodothyronine; D013972:Thyrotropin; D011078:Polychlorinated Biphenyls; D013974:Thyroxine