title: Dioxin-like exposures and effects on estrogenic and androgenic exposures and micronuclei frequency in mother-newborn pairs.
abstract: In utero exposure to environmental dioxin-like, estrogen and androgen compounds can cause adverse health effects. Little is known about potential interactions in vivo between dioxin-like compounds, estrogens and androgens during fetal development in humans. Therefore we explored the potential interactions in vivo between dioxin-like compounds, estrogens, androgens using chemical-activated luciferase expression (CALUX)(R) bioassays in maternal and umbilical cord blood plasma concurrently collected at the time of planned Caesarean section from 98 healthy pregnancies. The dioxin-like activity was also determined after placental transfer of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the ex vivo human placenta perfusion system. Similar dioxin-like activity in maternal and cord blood (37 versus 33pg CALUX(R)-TEQ/g plasma lipids, P>0.05) was detected and it demonstrates transplacental transfer. Increased dioxin-like activity in the perfused placenta tissue after ex vivo TCDD perfusions (from 17 to 280pg CALUX(R)-TEQ/g plasma lipids) suggest that accumulation in the placenta prevents immediate transplacental transfer of TCDD. Androgenic activity were also similar in the paired mother-newborns (0.10 versus 0.18ng CALUX(R)-AEQ/mL plasma), whereas cord blood plasma estrogenic activity was higher than maternal levels (22.6 versus 18.5ng CALUX(R)-EEQ/mL plasma). In cord blood plasma androgenic activity was strongly positively associated with maternal levels (Rs=0.8, P<0.001) whereas dioxin-like and estrogenic activities were modestly associated with maternal levels (Rs</=0.4, P<0.001). The micronuclei frequency, an indicator of genetic instability was significantly associated with dioxin-like activity in cord blood, independently of other recorded factors (Rs=0.4, P<0.003). This study demonstrated interactions in vivo between dioxin-like, estrogenic and androgenic exposures during fetal development of humans.
authors.affiliation: Section of Environmental Health, Department of Public Health, University of Copenhagen, Oester Farimagsgade 5A, 1353 Copenhagen K, Denmark. Electronic address: marp@sund.ku.dk.
authors.forename: Marie
authors.initials: M
authors.lastname: Pedersen
authors.affiliation: Faculty of Food Science and Nutrition, School of Health Sciences, University of Iceland, Hjarðarhagi 2-6, 107 Reykjavík, Iceland; Maternal Nutrition Group, Department of Epidemiology, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen S, Denmark. Electronic address: Lur@ssi.dk.
authors.forename: Thorhallur I
authors.initials: TI
authors.lastname: Halldorsson
authors.affiliation: Section of Environmental Health, Department of Public Health, University of Copenhagen, Oester Farimagsgade 5A, 1353 Copenhagen K, Denmark. Electronic address: lima@sund.ku.dk.
authors.forename: Line
authors.initials: L
authors.lastname: Mathiesen
authors.affiliation: Section of Environmental Health, Department of Public Health, University of Copenhagen, Oester Farimagsgade 5A, 1353 Copenhagen K, Denmark. Electronic address: tina@sund.ku.dk.
authors.forename: Tina
authors.initials: T
authors.lastname: Mose
authors.affiliation: BioDetection Systems B.V., Science Park 406, 1098 XH Amsterdam, The Netherlands. Electronic address: Bram.Brouwer@bds.nl.
authors.forename: Abraham
authors.initials: A
authors.lastname: Brouwer
authors.affiliation: Department of Obstetrics, University Hospital of Copenhagen, Blegdamsvej 9, 2100 Copenhagen Oe, Denmark. Electronic address: Morten.Hedegaard@rh.dk.
authors.forename: Morten
authors.initials: M
authors.lastname: Hedegaard
authors.affiliation: Section of Environmental Health, Department of Public Health, University of Copenhagen, Oester Farimagsgade 5A, 1353 Copenhagen K, Denmark. Electronic address: stl@sund.ku.dk.
authors.forename: Steffen
authors.initials: S
authors.lastname: Loft
authors.affiliation: Department of Health Risk Analysis and Toxicology, University of Maastricht, Universiteitssingel 50, 6229 ER Maastricht, The Netherlands. Electronic address: J.Kleinjans@grat.unimaas.nl.
authors.forename: Jos C S
authors.initials: JCS
authors.lastname: Kleinjans
authors.affiliation: BioDetection Systems B.V., Science Park 406, 1098 XH Amsterdam, The Netherlands. Electronic address: Harrie.Besselink@bds.nl.
authors.forename: Harrie
authors.initials: H
authors.lastname: Besselink
authors.affiliation: Section of Environmental Health, Department of Public Health, University of Copenhagen, Oester Farimagsgade 5A, 1353 Copenhagen K, Denmark. Electronic address: liek@sund.ku.dk.
authors.forename: Lisbeth E
authors.initials: LE
authors.lastname: Knudsen
mesh_terms: D000328:Adult; D000728:Androgens / Q000633:toxicity*; D001681:Biological Assay / Q000379:methods; D004147:Dioxins / Q000633:toxicity*; D004781:Environmental Exposure; D004785:Environmental Pollutants / Q000633:toxicity*; D004967:Estrogens / Q000633:toxicity*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D017930:Genes, Reporter; D006801:Humans; D007231:Infant, Newborn; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced*; D009035:Mothers; D010920:Placenta / Q000737:chemistry; D010949:Plasma / Q000737:chemistry; D011247:Pregnancy; D055815:Young Adult
chemical_list: D000728:Androgens; D004147:Dioxins; D004785:Environmental Pollutants; D004967:Estrogens; D008156:Luciferases