Estrogenicity of food-associated estrogenic compounds in the fetuses of female transgenic mice upon oral and IP maternal exposure.
The present study investigated to what extent seven food-associated in vitro estrogenic compounds can induce estrogenic effects in the fetuses of pregnant female mice with an estrogen receptor (ER)-mediated luciferase (luc) reporter gene system. The luc-induction was determined either 8h after maternal dosing with a single intraperitoneal (IP) dose or 24h after the last of a series of 8 daily oral dosages. Three known estrogens, 17beta-estradiol (E(2)), 17 alpha-ethynylestradiol (EE) and 17beta-estradiol 3,17-dipropionate (EP) were used as positive controls at 1mg/kgbw and DMSO as solvent control. The food-associated estrogenic compounds tested were: bisphenol A (BPA), nonylphenol (NP) both at 50mg/kgbw, dichlorodiphenyldichloroethylene (p,p'-DDE) at 50mg/kgbw, quercetin at 16.6 mg/kgbw, and di-isoheptyl phthalate (DIHP), di-(2-ethylhexyl) phthalate (DEHP) and di-(2-ethylhexyl) adipate (DEHA) all at 100mg/kgbw. Exposure to E(2), EE and EP resulted in significant luc inductions upon both oral and/or IP dosing in a variety of tissues including liver, tibia and femurs, and upon IP dosing also in fetuses. BPA, NP, DEHA, DEHP, DIHP, DDE and quercetin were unable to significantly induce luc activity in fetuses. However, after maternal oral exposure during gestation to NP, BPA and DIHP placental luc activity was significantly lowered. The results indicate that at the current levels of exposure to food-associated estrogenic compounds, estrogenic effects to the fetus are not expected. The significant luc reduction in the placenta, should be further studied for its significance for fetal development and relevance for the human situation.
Toxicology Section, Wageningen University, Tuinlaan 5, 6703 HE, Wageningen, The Netherlands.
Marcel G R
MG
Ter Veld
E
E
Zawadzka
Ivonne M C M
IM
Rietjens
Albertinka J
AJ
Murk
D000284:Administration, Oral; D000818:Animals; D052244:Endocrine Disruptors / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D004967:Estrogens / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D005260:Female; D005333:Fetus / Q000187:drug effects* / Q000378:metabolism; D005506:Food Contamination; D017930:Genes, Reporter; D005865:Gestational Age; D007274:Injections, Intraperitoneal; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D008431:Maternal-Fetal Exchange; D051379:Mice; D008822:Mice, Transgenic; D038081:Organogenesis / Q000187:drug effects; D048789:Phytoestrogens / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D011247:Pregnancy; D011960:Receptors, Estrogen / Q000187:drug effects* / Q000235:genetics; D013997:Time Factors
D052244:Endocrine Disruptors; D004967:Estrogens; D048789:Phytoestrogens; D011960:Receptors, Estrogen; D008156:Luciferases