F An Animal Has Been Thyroidectomized, What Hormone(S) Would Be Missing In Its Blood?
Environ Health Perspect. 2005 Aug; 113(8): 1039–1045.
Enquiry
Thyroid Hormones in Pregnancy in Relation to Environmental Exposure to Organochlorine Compounds and Mercury
Larissa Takser
1Laboratoire de Physiologie Materno-fœtale,
2Centre de Recherche BioMed, and
Donna Mergler
iiiCINBIOSE (Centre d'étude des interactions biologiques entre la santé et l'environnement), Université du Quebec à Montréal, Montréal, Quebec, Canada
Mary Baldwin
threeCINBIOSE (Middle d'étude des interactions biologiques entre la santé et l'environnement), Université du Quebec à Montréal, Montréal, Quebec, Canada
Sylvie de Grosbois
3CINBIOSE (Center d'étude des interactions biologiques entre la santé et l'environnement), Université du Quebec à Montréal, Montréal, Quebec, Canada
Audrey Smargiassi
3CINBIOSE (Centre d'étude des interactions biologiques entre la santé et fifty'environnement), Université du Quebec à Montréal, Montréal, Quebec, Canada
Julie Lafond
1Laboratoire de Physiologie Materno-fœtale,
2Eye de Recherche BioMed, and
Received 2004 Oct 21; Accepted 2005 May 23.
Abstract
Polychlorinated biphenyls (PCBs), chlorinated pesticides, and mercury are global environmental contaminants that can disrupt the endocrine arrangement in animals and humans. However, there is petty evidence that they can interfere with endocrine status in meaning women and neonates at low levels of exposure. The aim of this study was to examine thyroid hormone levels during pregnancy and in string blood in relation to blood concentrations of organochlorine compounds (OCs) and Hg in healthy women recruited during pregnancy. We found a pregnant negative correlation between maternal full triiodothyronine levels and iii not-coplanar congeners (PCB-138, PCB-153, and PCB-180), iii pesticides (p,p′-DDE, cis-nanochlor, and hexachlorobenzene), and inorganic Hg independently, without any other changes in thyroid status. No pregnant relationships were observed between OCs and cord serum thyroid hormones. Cord serum free thyroxin was negatively correlated with inorganic Hg. These results suggest that at even low levels of exposure, persistent environmental contaminants can interfere with thyroid condition during pregnancy.
Keywords: cord blood, surroundings, mercury, pesticide, polychlorinated biphenyls, pregnancy, thyroid
Acceptable thyroid operation during pregnancy is a known determinant of healthy pregnancy outcomes and successful brain development in the fetus (LaFranchi et al. 2005). Recent epidemiologic studies take focused on subclinical maternal thyroid deficiency during pregnancy, peculiarly for hypothyroxinemia in early on gestation, and its long-term effects on psychomotor development in children (Pop et al. 2003). These furnishings could be mediated by dumb glucose metabolism in fetal encephalon during the critical period of neuroblast proliferation (Pickard et al. 1999). In addition, the trophoblast has a high binding capacity for triiodothyronine (Tthree), and it has been suggested that the placenta is a thyroid hormone (TH)–dependent tissue (Kilby et al. 1998; Oki et al. 2004).
Experimental studies take shown that polychlorinated biphenyls (PCBs) and related chemicals decrease circulating THs during development (Donahue et al. 2004; Ulbrich and Stahlmann 2004; Zoeller et al. 2000). Prenatal or postnatal exposition of humans or animals to PCBs can upshot in hormonal changes and neurodevelopmental deficits (Jacobson and Jacobson 2002, 2003; Vreugdenhil et al. 2002a, 2002b, 2004). In rats, Goldey et al. (1995) reported that ototoxic effects of PCBs were associated with decreased circulating THs after perinatal exposure. It has besides been suggested that interference with endocrine systems, particularly the thyroid, could be one possible explanation for PCB-induced psychomotor filibuster observed in several cohort studies (Winneke et al. 2002).
Ii classes of PCB metabolites are formed from PCB biotransformation: hydroxylated (OH-PCBs) and methyl sulfone PCBs. No data are available about human exposure to methyl sulfone PCBs or their furnishings on thyroid condition in experimental animals. Nonetheless, most PCB congeners and hydroxylated PCBs, which disrupt Thursday condition, are transferred across the placenta to the fetus in concentrations resulting in levels of approximately 50% and thirty%, respectively, of those in maternal plasma (Soechitram et al. 2004). Hydroxylated PCBs show high binding affinity for the serum Th-binding protein transthyretin, thus displacing the natural ligand, thyroxin (T4; Cheek et al. 1999). PCBs, as well as some other organochlorine compounds (OCs) such every bit hexachlorobenzene, are also known to increase the activeness of hepatic drug-metabolizing enzymes, in item, uridine diphosphoglucuronosyl transferase (UDPGT), responsible for glucuronidation of T4 (Van Birgelen et al. 1995; van Raaij et al. 1993). In vitro, hydroxylated PCBs have a low affinity for the human thyroid receptor only practice have a Th-like analogousness for the serum transport poly peptide transthyretin (Cheek et al. 1999; Meerts et al. 2002) and inhibit the iodothyronine sulfotransferase action (Schuur et al. 1998).
Chlorine substitution in the phenyl rings gives each PCB its own target and mechanism of toxicity. "Coplanarity" of PCB phenyl rings and "laterality" of chlorine atoms are important structural features that determine specific binding behavior with proteins and certain adverse responses in biologic systems. There is evidence that coplanar PCB mutagenic toxicity is mediated through the aryl hydrocarbon (Ah) receptor (Rubber 1994). Recently, it was reported that both mono-ortho and non-coplanar types of PCBs, and hydroxylated PCB metabolites may disrupt Thursday status, in role, by affecting thyroid hormone receptor (TR)-mediated transcription, which may influence growth and development of Thursday target organs, particularly in the cardinal nervous system (Iwasaki et al. 2002). Khan and Hansen (2003) suggest that non-coplanar congeners interfere with the hypothalamo-pituitary-thyroid (HPT) axis by producing a subnormal response of the pituitary and thyroid to thyrotropin releasing hormone (TRH) stimulation.
The developing fetus is peculiarly susceptible to thyrotoxic effects of PCBs and their metabolites. In rats, exposure to hydroxylated PCB 4′-OH-CB-108 from gestational day (GD)10 to GD16 decreased maternal, fetal, and neonatal plasma full T4 and gratis Tiv (fT4) in a dose-dependent manner (Meerts et al. 2002). Chronic developmental exposure to Aroclor 1254 from GD6 to postpartum day 21 also reduces circulating levels of total T4 (Zoeller et al. 2000). At the aforementioned conditions of exposure, Goldey et al. (1995) observed decreased total T4 levels and a moderate reduction of Tthree levels in offspring at high doses of exposure.
Other environmental pollutants, such as pesticides and mercury, may also disrupt thyroid function (Bristles and Rawlings 1999; Ellingsen et al. 2000; Rathore et al. 2002; Watanabe et al. 1999). Long-term workplace exposure to Hg interferes with thyroid metabolism by reducing T4 deiodination (Ellingsen et al. 2000). In a community highly exposed to hexachlorobenzene, a meaning positive association was found between this OC and concentrations of thyroid-stimulating hormone (TSH) at nascency (Ribas-Fito et al. 2003).
The full general population is exposed to multiple environmental contaminants at relatively low doses, but few studies have reported thyroid status in pregnancy in relation to mixtures of environmental organic pollutants. Moreover, nearly studies report the sum of PCBs (∑PCB) as an exposure measure, which can mask the specific effect of different groups of congeners with different mechanism of action. Thus, the objective of the present report was to examine the relation between exposure to potential endocrine-disrupting chemicals (coplanar and non-coplanar PCBs, organochloride pesticide residues, and Hg) and thyroid condition in meaning women and the newborn.
Materials and Methods
Report population.
The women participating in the written report were recruited at their first prenatal visit at the Centre for Local Customs Services (function of the National Public Wellness System) in Southwest Québec. After signing a consent course, each woman filled out an interview-administered questionnaire, which contained full general sociodemographic data and information on residency, medical history, drinking and smoking habits, and nutrition, and blood samples were obtained. Those who were recruited into the study during the first trimester (before the 13th week) provided a beginning sample at entry and a 2d during the second trimester, whereas those who were recruited betwixt the 14th and 24th weeks provided 1 sample before delivery. The start trimester sampling was performed earlier the outset ultrasound examination. The gestational age at sampling was revised according to ultrasound information for 22 women, who provided two samples at the second trimester. The study population consisted of 149 significant women, 101 of whom gave birth at the participating hospital where maternal and cord blood samples and placental tissue were obtained at commitment. Two weeks afterward nascency, a second questionnaire was interview administered. This 2nd questionnaire included information on medical and obstetrical history, nascence data, and smoking and drinking during pregnancy.
After verification, simply twoscore women had entered the study during the first 13 weeks of pregnancy, and 109 entered at the 2nd trimester. Thus, virtually data were available for the second trimester (due north = 149). At commitment, there were 101 maternal and 92 cord blood samples available for analyses. Thus, complete data throughout pregnancy were bachelor for 38 women, and for 101 from the second trimester and at commitment. Data for hormones and contaminants are missing for some women (n = 2–4) because of insufficient quantity of blood or nonrespect of specimen storage protocol.
Biologic sampling.
Blood samples for the start and second trimesters were collected at the pregnant women's residences after night fasting, whereas the third-trimester samples and cord blood samples were taken at the hospital at delivery. Whole blood and serum samples were refrigerated at −20°C until contaminant and hormone conclusion (iii–four months).
PCBs, pesticides, and Hg determination.
Laboratory analyses of PCBs and chlorinated pesticides were performed past the Centre of Toxicology of Québec by gas chromatography coupled with mass detection using a chromatograph (model 6890) and mass detector (model 5973) from Agilent (Mississauga, Canada). Blood plasma (ii mL) was extracted using an ammonium sulfate/ethanol/hexane mixture, cleaned upwards on Florisil columns, and taken to a final volume of 100 μL. Routine checks of accuracy and precision were performed using reference materials from the National Plant of Standards and Engineering science (Gaithersburg, Physician, Us). Also, periodic evaluations were carried out through participation in two external proficiency testing programs [Artic Monitoring Cess Programme band test; Laboratoire de toxicologie humaine/Institut national de santé publique (INSPQ) and the German language Society of Occupational and Environmental Medicine, Erlangen, Germany]. The detection limits were 0.02 μg/Fifty for PCB congeners and chlorinated pesticides.
Cold vapor diminutive absorption spectrometry was used to appraise total Hg (THg) and inorganic Hg (IHg) using a mercury monitor (model 100; Pharmacia Instruments, Piscataway, NJ, The states). Organic Hg (OHg) was calculated every bit the difference between THg and IHg. THg was determined using 500 μL blood digested with an equal volume of concentrated nitric acid. An aliquot of the digest was then introduced in the arrangement's reaction chamber (containing a reducing solution of cadmium chloride and stannous chloride). Hg vapor was generated and detected, and aqueous calibration was performed. The IHg fraction was determined using the same methodology except that cadmium chloride was omitted from the reactant mixture. Routine checks of accuracy and precision were performed using reference material from the Laboratoire de toxicologie humaine/INSPQ's interlaboratory comparing programme. In addition, periodic evaluations were carried out through participation in the same program. The detection limit obtained was two nmol/L (0.2 μg/50). Variation coefficients (n ~ twenty, different days) at levels of 38 nmol/L IHg and 82 nmol/50 OHg were iv and 3.4%, respectively.
The detection limits were determined from the analyses of 10 actual samples, whose concentrations were between four and 10 times the estimated detection limit. The standard difference of these 10 samples multiplied by 3 provided the detection limit, which was multiplied past 10 to provide the quantification limit.
Lipid determination.
Total and free cholesterol, triglycerides, and phospholipids were individually measured using enzymatic methods on the Technicon automated analyzer (model RA-500; Technicon, Cranesville, PA, Us) equally previously described (Moorjani et al. 1987). Plasma total lipids were calculated using the summation method: full lipids = 1.677 (total cholesterol − gratuitous cholesterol) + gratuitous cholesterol + triglycerides + phospholipids.
Thyroid hormone determination.
Thyroid hormones [TSH, total Tiii (TT3), and fT4] were analyzed by radioimmunoassay at the Clinical Biochemistry Service of Saint-François d'Assise hospital (Québec, Canada) (Forest et al. 1998).
Statistical assay.
All statistical analyses were performed using SAS (version 8.12; SAS Institute 1999). The log-ordinarily distributed data were log-transformed in club to use parametric tests. The stepwise procedure was used to test relationships betwixt variables of involvement and potential cofactors such as maternal age, smoking and alcohol consumption, child'due south sex and birth weight (for cord blood variables), gestational age at sampling, and full lipid concentrations. The relation betwixt exposure variables and effect variables was examined by longitudinal repeated measure out analysis (Mixed procedure) considering the within-field of study outcome and chemical compound symmetry covariance structure. Relationships between cord claret exposure and effect variables were tested using assay of covariance (general linear model procedure). Because a large number of samples had contaminant levels below the detection limit, the cord claret exposure levels were coded in two levels: detected/undetected for selected congeners, and to a higher place/below median for summed variables. PCB-101 and PCB-128 as well equally trans-chlordane, cis-chlordane, and aldrin were excluded from statistical assay because 100% were undetected values.
THs are involved in lipid metabolism, and the reduction in their circulating level in hypothyroid subjects is associated with an atherogenic lipid contour (Al Tonsi et al. 2004). Therefore, in order to take into consideration the furnishings of THs on blood lipid mobilization, analyses both adapted and unadjusted for lipid concentration were performed. Two kinds of physiologic sequences are possible in the tested relationship betwixt lipophilic contaminants such as PCBs or pesticides, and THs: first, the hypothesized relation that increased lipids lead to increased blood PCBs, which pb to decreased TH levels; and second, an inverse relation where decreased THs lead to increased lipids, which lead to increased blood PCBs. The comparison of two models, adjusted and non lipid-adjusted, can point whether lipids are a confounding factor in a hypothesized relation or an intermediate factor in the changed link. The lipid concentration variables were introduced in linear models equally stock-still variables. The criterion for significance was set at p < 0.05.
In order to demonstrate the cumulative effect of studied pollutants, we defined two groups of subjects based on the degree of their exposure to five OCs significantly related to hormone levels: PCB-138, PCB-153, PCB-180, p,p′-dichlorodiphenyldichloroethylene (p,p′-DDE), and hexachlorobenzene. The exposed group included women who had two or more pollutant levels higher than the 75th percentile of distribution, and the nonexposed grouping included those with none or only one pollutant level higher than the 75th percentile.
Results
Population characteristics.
The women who gave nativity (n = 101) averaged 27 years of historic period (range, xv–39 years); 30% smoked during pregnancy, and 8% consumed alcohol moderately (0.5–2 drinks/calendar week, iv–thirty g of alcohol/week). During pregnancy, eleven women (10%) had gestational diabetes, 2 of those with pregnancy-induced hypertension; 11 women had pregnancy-induced hypertension without gestational diabetes, 2 of those with proteinuria. Five percent of births occurred earlier 37 weeks of pregnancy, the average birth weight was iii.3 kg (range, 1.ix–5.0 kg), and 51% of newborns were boys. The characteristics of women lost to follow-up (north = 48) were not significantly dissimilar from those giving birth at participating motherhood hospitals.
Hormone and contaminant levels during pregnancy and at nascency.
The TH concentrations are shown in Table one, and Tables 2 and 3 present the blood PCB congener and pesticide levels. We observed that TTthree and TSH levels increased during pregnancy, whereas fT4 levels decreased. TH levels in this population of pregnant women are similar to data reported by de Escobar et al. (2004). The cord blood PCB concentrations were significantly lower than maternal blood and, in most samples, lower than detection limit level.
Table 1
Blood levels of hormones during pregnancy and at birth.
| First trimester (due north = 40) | 2d trimester (n = 147)a | At commitment (n = 100) | Cord blood (n = 92) | |||||
|---|---|---|---|---|---|---|---|---|
| Median | fifth–95th percentiles | Median | 5th–95th percentiles | Median | 5th–95th percentiles | Median | 5th–95th percentiles | |
| TSH, mIU/L | two.1 | 0.09–ix.55 | 2.2 | 0.62–5.v | two.6 | 0.viii–seven.53 | 9.8 | 3.4–30.four |
| fT4, pmol/50 | 14.iii | 11.five–18.seven | 12.eight | ten.2–15.eight | 11.6 | 8.7–15.05 | sixteen.1 | 12.8–nineteen.6 |
| TTthree, nmol/50 | 2.7 | 1.97–3.6 | 3.2 | 2.3–4.2 | three.iii | 2.4–four.5 | 1.3 | 0.nine–1.ix |
Table two
Concentrations of plasma PCB congeners (μg/L) shown every bit median (5th–95th percentiles) or pct of samples above detection limit.
| Congener | First trimester (due north = 39) | Second trimester (n = 145) | At commitment (n = 101) | Cord blood (northward = 92) |
|---|---|---|---|---|
| PCB-28 | ten% | 28% | 21% | 2% |
| PCB-52 | 0% | ii% | four% | ane% |
| PCB-99 | 0.02 (ND–0.05) | 0.02 (ND–0.05) | 0.02 (ND–0.06) | six% |
| PCB-101 | 0% | 0% | 0% | 0% |
| PCB-105 | 3% | 12% | 23% | 8% |
| PCB-118 | 0.02 (ND–0.08) | 0.03 (ND–0.08) | 0.03 (ND–0.x) | 33% |
| PCB-128 | 0% | 0% | 0% | 0% |
| PCB-138 | 0.06 (0.02–0.18) | 0.07 (0.03–0.20) | 0.08 (0.03–0.25) | 0.02 (ND–0.06) |
| PCB-153 | 0.07 (0.03–0.26) | 0.08 (0.03–0.27) | 0.09 (0.04–0.30) | 0.02 (ND–0.08) |
| PCB-156 | 0.02 (ND–0.05) | 0.02 (ND–0.05) | 0.02 (ND–0.07) | 37% |
| PCB-170 | 0.01 (ND–0.07) | 0.02 (ND–0.07) | 0.02 (ND–0.07) | 7% |
| PCB-180 | 0.04 (0.02–0.fourteen) | 0.05 (0.02–0.17) | 0.05 (0.02–0.19) | 0.01 (ND–0.05) |
| PCB-183 | 8% | fifteen% | 27% | 1% |
| PCB-187 | 0.02 (ND–0.06) | 0.02 (ND–0.05) | 0.02 (ND–0.06) | 14% |
| ∑ Mono-ortho coplanar PCBsa | 0.06 (ND–0.14) | 0.06 (ND–0.15) | 0.07 (0.04–0.18) | 0.04 (ND–0.07) |
| Total PCBs | 0.33 (0.16–1.31) | 0.35 (0.18–one.05) | 0.39 (0.20–i.22) | 0.16 (ND–0.35) |
Table 3
Blood Hg and plasma pesticide concentrations (μg/Fifty) shown as median (5th–95th percentiles) or percent of samples above detection limit.
| Start trimester (n = 39) | 2nd trimester (n = 145) | At delivery (northward = 101) | Cord blood (due north = 92) | |
|---|---|---|---|---|
| THg | 0.eighty (0.40–2.xx) | 0.60 (ND–2.0) | 0.sixty (ND–1.two) | 0.lx (ND–i.6) |
| OHg | 0.40 (ND–1.40) | 0.20 (ND–i.20) | 0.20 (ND–0.80) | 0.30 (ND–1.thirty) |
| trans-Nanochlor | 0.03 (ND–0.09) | 0.04 (0.02–0.x) | 0.05 (ND–0.xv) | fourteen% |
| Oxychlordane | 0.02 (ND–0.06) | 0.03 (0.02–0.07) | 0.03 (0.02–0.08) | x% |
| Mirex | 19% | fifteen% | 20% | 1% |
| Hexachlorobenzene | 0.04 (0.03–0.x) | 0.06 (0.03–0.11) | 0.06 (0.04–0.12) | 0.02 (0.01–0.05) |
| DDT | 0.01 (ND–0.04) | 0.03 (ND–0.05) | 0.04 (ND–0.07) | 11% |
| p,p′-DDE | 0.38 (0.16–0.90) | 0.43 (0.22–0.97) | 0.47 (0.20–ane.20) | 0.xvi (0.08–0.40) |
| cis-Nanochlor | 0% | i% | xx% | 0% |
| trans-Chlordane | 0% | 0% | 0% | 0% |
| cis-Chlordane | 0% | 0% | 0% | 0% |
| β -BHC | 0.03 (ND–0.05) | 0.04 (ND–0.08) | 0.05 (ND–0.09) | 1% |
| Aldrin | 0% | 0% | 0% | 0% |
In general, unadjusted blood PCB congener concentrations appeared to increment during pregnancy. However, when adapted for the increment of lipid mobilization during pregnancy, concentrations were like throughout. In women with gestational diabetes, unadjusted PCB levels were significantly higher at delivery than in nondiabetic women, only when adapted for lipid levels, they were similar.
Exposure and hormonal status: cofactors related to retained variables.
The relationships between variables of interest (maternal and string blood TSH, TT3, fT4, PCBs, pesticides, and Hg concentrations) were tested with respect to the following cofactors: maternal age, gestational historic period at sampling, cigarette smoking, booze use, nascency weight, newborn's sex, and plasma full lipid contents. Maternal age, gestational historic period at sampling, plasma total lipid content, and cigarette smoking during pregnancy were related to almost maternal biochemical measures (data not shown) and were added in final mixed models. For cord blood measures, total lipid levels, maternal age, birth weight, gestational age at birth, and cigarette smoking during pregnancy were associated with cord claret hormone levels and exposure variables.
Relationships between TH levels and plasma PCBs, pesticides, and Hg concentrations in pregnant women.
Tabular array 4 presents the results from mixed models including TSH, fTfour, and TTthree levels during pregnancy in relation to plasma PCB concentrations. In both lipid-adjusted and nonadjusted models, but TT3 levels were strongly negatively related to PCB concentrations, peculiarly to non-coplanar congeners (PCB-138, PCB-153, and PCB-180). No relation was observed with the sum of mono-ortho coplanar congeners (PCB-105, PCB-118, and PCB-156; ∑mono-ortho coplanar PCBs). PCB-180 was positively correlated with TSH levels but not with fT4 levels.
Table 4
Hormone levels and PCBs concentrations during pregnancy.
| TSH (mIU/L) | fT4 (pmol/Fifty) | TTthree (nmol/L) | ||||
|---|---|---|---|---|---|---|
| Unadjusted | Adjusteda | Unadjusted | Adjusteda | Unadjusted | Adjusteda | |
| ∑ PCB (μg/Fifty) | ||||||
| Gauge | 0.65 | 0.45 | −0.08 | 0.49 | −0.37 | −0.47 |
| df | 151 | 148 | 151 | 148 | 151 | 148 |
| Type three F-value | 0.50 | 0.21 | 0.05 | 1.6 | half dozen.4* | 9.6** |
| ∑ mono-ortho coplanar PCBsb (μg/L) | ||||||
| Guess | three.0 | 0.46 | −ii.vi | two.7 | −one.3 | −two.1 |
| df | 151 | 148 | 151 | 148 | 151 | 148 |
| Blazon 3 F-value | 0.xiii | 0.0 | 0.threescore | 0.62 | 0.98 | 2.27 |
| PCB-138 (μg/L) | ||||||
| Estimate | 0.90 | −0.55 | −0.48 | 3.1 | −two.i | −2.8 |
| df | 151 | 148 | 151 | 148 | 151 | 148 |
| Type 3 F-value | 0.03 | 0.01 | 0.05 | two.one | 7.2** | 11.2** |
| PCB-153 (μg/L) | ||||||
| Guess | −0.xviii | −0.93 | 0.57 | 2.5 | −ane.2 | −1.5 |
| df | 151 | 148 | 151 | 148 | 151 | 148 |
| Type 3 F-value | 0.0 | 0.08 | 0.xix | iii.vi | 5.ix* | 8.6** |
| PCB-180 (μg/50) | ||||||
| Gauge | vii.eight | 7.5 | −i.4 | −0.27 | −1.2 | −ane.4 |
| df | 151 | 148 | 151 | 148 | 151 | 148 |
| Type 3 F-value | 5.3* | 4.6* | one.1 | 0.04 | 6.0* | 7.vii** |
Concordant results were obtained when the correlation with plasma pesticides was examined. Hexachlorobenzene, cis-nanochlor, and p,p′-DDE concentrations were negatively related to TT3 levels in mothers in lipid-adjusted models. Blood IHg was as well negatively related to TT3 levels (Table 5). In addition, cis-nanochlor, when detected, was positively correlated with fT4 levels.
Tabular array 5
Hormone levels, Hg, and pesticides concentrations during pregnancy.
| TSH (mIU/50) | fT4 (pmol/L) | TTiii (nmol/Fifty) | ||||
|---|---|---|---|---|---|---|
| Unadjusted | Adjusteda | Unadjusted | Adjusteda | Unadjusted | Adjusteda | |
| OHg (μg/L) | ||||||
| Estimate | 0.58 | — | −0.eighteen | — | 0.05 | — |
| Type iii F-value | 0.50 | — | 0.34 | — | 0.18 | — |
| IHg (μg/L) | ||||||
| Estimate | −0.41 | — | −0.26 | — | −0.27 | — |
| Type 3 F-value | 0.28 | — | 0.57 | — | 4.20* | — |
| trans-Nanochlor (μg/L) | ||||||
| Estimate | −0.66 | −i.9 | −five.3 | −1.65 | −0.fifty | −0.91 |
| Blazon 3 F-value | 0.01 | 0.09 | 3.fourscore | 0.40 | 0.20 | 0.fourscore |
| Oxychlordane (μg/L) | ||||||
| Estimate | 10.3 | 4.half dozen | −seven.8 | 3.ix | −four.1 | −4.6 |
| Blazon iii F-value | 0.46 | 0.08 | 1.53 | 0.37 | 2.96 | three.fifteen |
| Mirex, detected vs. undetected | ||||||
| Gauge | 0.09 | 0.03 | −0.11 | 0.13 | 0.07 | 0.08 |
| Blazon three F-value | 0.01 | 0.0 | 0.14 | 0.19 | 0.36 | 0.41 |
| Hexachlorobenzene (μg/L) | ||||||
| Approximate | −five.4 | −eleven.0 | −2.3 | 8.1 | −3.4 | −five.2 |
| Type 3 F-value | 0.20 | 0.82 | 0.twenty | 2.91 | iii.83 | 7.51** |
| Ddt (μg/Fifty) | ||||||
| Estimate | −8.v | −14.2 | −0.89 | nine.ix | 1.39 | 0.26 |
| Type 3 F-value | 0.3 | 0.viii | 0.02 | ii.8 | 0.iv | 0.01 |
| p,p′-DDE (μg/L) | ||||||
| Estimate | 0.25 | −0.06 | −0.75 | 0.09 | −0.37 | −0.54 |
| Blazon 3 F-value | 0.04 | 0.0 | 2.0 | 0.03 | three.three | half-dozen.1* |
| cis-Nanochlor, detected vs. undetected | ||||||
| Estimate | 0.67 | 0.41 | 0.33 | 0.74 | −0.34 | −0.35 |
| Blazon 3 F-value | 0.36 | 0.13 | 0.73 | three.92 | 5.33* | 5.40* |
| β -BHC (μg/L) | ||||||
| Approximate | −two.one | −v.4 | ii.3 | viii.8 | −2.4 | −3.4 |
| Blazon iii F-value | 0.04 | 0.2 | 0.3 | iv.2* | two.0 | 3.8 |
Effigy i illustrates the change of TT3 and fTiv levels during pregnancy by group of exposure to five pollutants that are significantly related to TT3 levels in previous analyses (PCB-138, PCB-153, PCB-180, p,p′-DDE, and hexachlorobenzene). For the women in the nonexposed group (none or 1 of these pollutant levels college than the 75th percentile of distribution), TTiii levels significantly increased from the second trimester to delivery; for the women from the exposed group (2 or more pollutant levels higher than the 75th percentile), TTiii levels decreased. Moreover, this relationship was much more significant than those in women classified according to whatsoever OC level higher than 75th percentile, separately (data non shown).
Change in TT3 (nM) and fT4 (pM) levels between 2nd trimester and delivery in significant women past grouping of exposure, adjusted to gestational historic period at sampling. p = 0.006 for TT3 but fTfour was not statistically meaning.
Relationships betwixt string blood plasma PCB, pesticide, and Hg concentrations and cord blood hormone levels.
In general, the PCB congeners and pesticide residues in cord plasma were not significantly related to string blood THs (data not shown). The string claret OHg was non significantly related to hormone levels. Only cord claret IHg was negatively related to fTfour level (adjusted hateful, 16.5 pmol/50 in subjects with undetected IHg vs. xv.5 pmol/Fifty in those with detected values; partial Spearman r = −0.26, p = 0.02).
Word
Our results demonstrate a meaning negative relationship between circulating TT3 levels in pregnant women at depression environmental doses of PCB-138, PCB-153, PCB-180, IHg, and two pesticides, p,p′-DDE and hexachlorobenzene. In addition, but cis-nanochlor, in women having detected values, was related to both increased fTfour and decreased TT3, during pregnancy. No other significant relation was observed in regard to fT4 or TSH levels. No clan was observed betwixt string blood organic pollutant concentrations and TH levels, except for the negative correlation between IHg and fTiv in cord blood serum. The results from the Dutch cohort study (Koopman-Esseboom et al. 1994) show a decrease in maternal T3 and T4 in pregnancy and in baby TSH levels in relation to toxic equivalents of milk PCB dioxin-similar and non-coplanar congeners. These authors besides noted that higher levels of maternal and string blood plasma PCB-118, PCB-138, PCB-153, and PCB-180 correlated significantly with college plasma TSH levels in infants in the second week later on birth. College levels of iii not-coplanar congeners (PCB-137, PCB-138, and PCB-153) in human milk too correlated significantly with higher TSH levels in umbilical claret plasma. In some other study, which investigated string blood for TSH in relation to the aforementioned congeners (PCB-118, PCB-138, PCB-153, and PCB-180), no relation between PCBs and TSH was plant (Ribas-Fito et al. 2003), merely other THs (T3, T4) were not measured. In a report on the effects of exposure to methylmercury on thyroid function at nascency, Steuerwald et al. (2000) found no relation with Hg levels, simply cord blood resin-Tthree uptake levels were negatively correlated with the not-coplanar PCBs in maternal blood samples. The lowering of resin-Tthree uptake is one indicator of master or secondary hypothyroidism. Thus, thyroid-binding globulin (TBG) levels rose in cord claret with increased maternal PCB exposure.
The lack of human relationship in regard to cord blood THs in our report could be related to other biologic factors such as iodine and selenium intake or circadian variation (Andersen et al. 2003; Beckett et al. 2005), which are likely to influence endogenous hormone homeostasis, every bit well as to the very depression level of exposure in fetal tissues. Exposure levels to PCB congeners in this population were 3–45 times lower than in previously reported studies [reviewed past Longnecker et al. (2003)]. In addition, fetal TBG and other binding proteins are low (Hume et al. 2004), which could protect the fetus from toxic furnishings of chemicals that deed on TH bounden. Also, thyroid condition tin can be disrupted by other factors not measured in the present written report, including ecology pollutants such as pentachlorophenol (PCP) or OH-PCBs, which are metabolites of hexachlorobenzene and PCBs, respectively, as was reported previously in another Québec population (Sandau et al. 2002). These authors reported negative correlations between cord plasma costless T3 and T4, as well as TBG, with sum of PCP and OH-PCBs but not with PCB congeners individually or ∑PCB. Curiously, the concentrations of PCBs and OH-PCBs were also negatively correlated with TSH in cord plasma. Although these correlations were highly meaning, they were obtained from a small sample of newborns (north = xx) without whatsoever adjustment for misreckoning variables.
Similar to the nowadays results, the selective effect of PCBs on T3 levels has been reported in women who swallow fish (Hagmar et al. 2001) (north = 32); in that written report, the PCB-153 concentration was negatively related to TT3 levels. Osius et al.'south (1999) report of schoolchildren showed that PCB-138, PCB-153, and PCB-180 levels were negatively related to free T3 levels without whatever significant change in TSH or T4 concentrations; this human relationship was significant only in girls. To our knowledge, these are the just two studies that have demonstrated a more than pronounced event on T3 than on T4. However, in physiologic and pathologic conditions the isolated reduction of T3 levels is rarely observed considering there are constructive compensatory mechanisms via Tfour product.
The results of the present study indicate that claret lipid content is non a major confounding cistron for the relationship betwixt THs and OCs. Both lipid-adapted and unadjusted models revealed the aforementioned degree of significance for OC exposure. Thus, the rise of lipids after the TH decrease is unlikely to be an intermediate factor of the observed relationships.
Although epidemiologic studies cannot explore precise mechanisms of observed statistical relationships, some mechanistic hypotheses tin can be proposed. The deiodination machinery could exist hypothesized to explicate observed decrease in T3 levels in relation to exposure to OCs and Hg. As reviewed past Bianco et al. (2002), the T3 degradation by type 3 deiodinase (D3), which catalyzes the inner ring deiodination of Tiv to reverse T3 (rT3) and of T3 to 3,iii′-T2, represents an of import pathway for the inactivation of THs. D3 shows substrate preference for T3 over T4 and is expressed at high levels in homo placental tissue (Huang et al. 2003). The overexpression of D3, called "consumptive hypothyroidism" and reported in infantile hemangiomas, is characterized by undetectable serum T4 and T3 and high rT3 levels. Our results could be related to direct or indirect consecration of D3 activity or its increased expression, but nosotros did non assess the gratuitous T3 or rTiii levels to confirm this hypothesis. This needs further experimental research at low levels of OC exposure. In addition, an increase in placental D3 activity in methylmercury-exposed mice has been reported (Watanabe et al. 1999). Interestingly, the brain D3 activity was depressed in the fetuses from exposed dams. In our written report, it is difficult even so to explain the lack of association with cord serum Tthree given that placental D3 participates in fetal T3 degradation in humans (Santini et al. 1999).
Other types of deiodinases present in different tissues tin contribute to Tfour and Tiii deiodination. In humans, 80% of circulating T3, the physiologically active form of TH, is generated from peripheral deiodination of T4 by enzymatic action of 5′-monodeiodinase, and 20% is derived from thyroidal secretion (Pilo et al. 1990). At that place are two types of 5′-monodeiodinase enzyme: D1 is located at the plasma membrane, and D2 is associated with endoplasmic reticulum. The T3 generated by D1 does non have straight admission to nuclei but instead must showtime be exported into the plasma. Both D1 and D2 deiodinases contribute to plasma T3 content. The substrates for these enzymes are rTiii and T3 sulfate for D1, and T4 and rTthree for D2 (Bianco et al. 2002). However, serum T3 concentration remains normal in D1- or D2-deficient mice (Maia et al. 1995).
Several studies have explored the upshot of OCs on D1 and D2 deiodinase activity. I study reported the depression of liver D1 action in response to Aroclor 1242 and 1254 treatment in the chick embryo (Gould et al. 1999). Wade et al. (2002) examined the effect of subchronic exposure to circuitous mixture of persistent contaminants (sixteen OCs, lead, and cadmium) on THs in male person rats and reported increased TSH levels at the lowest level of exposure without any changes in Tfour or Tthree. Moreover, the authors observed pregnant reduction in hepatic D1 activity and speculated that the TSH increase could be related to pituitary D2 depression. In that location is a need for further investigations to explore the role of deiodinases in toxicity of environmental pollutants, such as PCBs and pesticides, in humans.
In addition to deiodination, TH is also metabolized by conjugation of the phenolic hydroxyl grouping with glucuronic acid or sulfate (Leonard and Köhrle 1996). This mechanism is also involved in OC toxicity. For example, hexachlorobenzene was shown to decrease full and fTiv levels in rats, without pregnant effect on T3 (Kleiman de Pisarev et al. 1990). Hexachlorobenzene decreased kidney and brown adipose tissue D1 activity after xv–21 days of exposure, but total body D1 activity was significantly increased. In improver, hexachlorobenzene increased the activity of hepatic Tfour UDPGT in a time-dependent mode without changes in T3-UDPGT (Alvarez et al. 2005). The aforementioned mechanism on T4-UDPGT was proposed to explain the subtract in T4 following PCB exposure (Barter and Klaassen 1994). However, we did not observe whatsoever negative association betwixt fT4 and OCs. Thus, we cannot consider an event on the enzyme responsible for TH conjugation as a possible explanation of these results. Nosotros observed, however, a negative human relationship betwixt fT4 in cord blood serum and IHg. If this relationship was not due to hazard, information technology may be related to inducing backdrop of IHg on UDPGT in renal tissue reported in mice (Tan et al. 1990). Moreover, workplace exposure to IHg was reported to exist associated with increases in T4, rTthree, and the Tfour:T3 ratio (Ellingsen et al. 2000), suggesting an inhibitory consequence of Hg on deiodinase activity. In our written report, IHg was associated with a decrease in maternal TT3 during pregnancy that could exist due to an upshot of Hg on deiodinase activeness. However, because the fTiv levels were non changed and gratis T3 was not adamant, this explanation remains speculative.
Bounden to TBG and/or to transthyretin, two major TH transporters in blood, could exist proposed equally an alternative hypothesis to explain the observed negative human relationship between OCs and TT3 levels during pregnancy. PCBs, particularly non-coplanar congeners, behave a structural resemblance to the endogenous THs and have a high affinity for Thursday-binding proteins such as transthyretin (Chauhan et al. 2000). Also, hydroxylated PCB metabolites bound to transthyretin with affinities similar to that of T4, but they have a low affinity for TBG (Cheek et al. 1999). Alteration of TH-binding capacity in serum is associated with variations in total TH concentration. Diminished serum TH values are observed in subjects with TBG deficiency. Yet, decreased concentration or analogousness of transthyretin is non associated with variations in serum concentrations of THs (Bartalena and Robbins 1992). Few data are available almost affinities of PCBs and pesticides to bind to TBG.
At that place are substantial and important differences between humans and animals with respect to structural characteristics of deiodinase enzyme and thyroid economy. In both rodents and humans, deiodinases are selenocysteine-containing proteins, and the presence of selenocysteine in the protein is critical for enzyme activity. All the same, the carboxy concluding of D1 from rat liver was unlike from that of other species (Santini et al. 1992). Also, the rat has a much larger contribution of Tthree secreted straight from the thyroid gland than humans. Information technology has been estimated that only approximately twenty% of plasma T3 in humans comes from thyroidal secretion, as opposed to about 40% in rats (Bianco et al. 2002). It has also been estimated that D1 catalyzes well-nigh half of the daily extrathyroidal Tiii production from T4 in the rat versus an estimate of 25% in humans (Bianco et al. 2002). There is also heterogeneity in the send of THs between species. In humans, THs are primarily bound to TBG. The remainder is jump to less-specific proteins, such equally albumin and transthyretin. These three proteins transport more than than 95% of THs (Barlow 1997; Bartalena and Robbins 1992). In growing rats, a significant deviation is that TBG is not found between 2 and 7 months of age, the historic period range typically used in basic toxicology studies (Vranckx et al. 1994). In adult rats, THs are leap to the depression-affinity carriers albumin and transthyretin. As a consequence, the half-life of THs is shorter in adult rats than in humans (McClain 1995). These diverse interspecies differences imply a different predisposition of rats compared with humans to perturbations of thyroid homeostasis past chemicals that influence thyroid condition (Lans et al. 1994).
One limitation of our study is the measure of TT3 and fTfour without costless Tthree and total T4 levels. The TTthree does non include rT3 and Tiii sulfate levels, which could assistance u.s. to confirm the hypothesis that PCB, pesticides, and Hg bear on Tfour or T3 deiodination. As well, we are unable to show if the observed human relationship is related to free T3 decrease or to Tthree fraction binding to TBG. Moreover, information technology is difficult to distinguish the proper effect of each OC on THs considering of their high collinearity (correlations between OCs > 0.sixty). Notwithstanding, their cumulative or synergistic effects tin can not exist excluded considering the most of import decrease of TT3 when it is correlated with more than one OC.
Thyroid condition is ofttimes assessed during pregnancy only limited routinely to measurements of TSH. Few data exist on the role of physiologic changes in thyroid condition in pregnant women and the effect of subtle T3 and Tiv variations on women's health. I study suggests that low free Tthree levels are associated with postpartum depression syndrome (Ijuin et al. 1998), but further investigations are needed to evaluate the long-term consequences of subtle thyroid changes related to environmental exposure to persistent organic contaminants. In conclusion, the potential of low-dose exposure to OC mixtures to interfere with hormonal status during pregnancy warrants further investigations with complete assessment of thyroid condition to confirm our results and to determine the short- and long-term consequences of these disturbances.
Footnotes
This study was funded by the Toxic Substances Research Initiative, Health Canada, and the Collaborative Mercury Research Network of the National Sciences and Technology Enquiry Council of Canada.
References
- Al Tonsi AA, Abdel-Gayoum AA, Saad M. The secondary dyslipidemia and deranged serum phosphate concentration in thyroid disorders. Exp Mol Pathol. 2004;76:182–187. [PubMed] [Google Scholar]
- Alvarez Fifty, Hernandez South, Martinez-de-Mena R, Kolliker-Frers R, Obregon MJ, Kleiman de Pisarev DL. The role of type I and type 2 5′ deiodinases on hexachlorobenzene-induced amending of the hormonal thyroid condition. Toxicology. 2005;207:349–362. [PubMed] [Google Scholar]
- Andersen S, Bruun NH, Pedersen KM, Laurberg P. Biologic variation is important for estimation of thyroid function tests. Thyroid. 2003;thirteen:1069–1078. [PubMed] [Google Scholar]
- Barlow JW. Lessons to the learned from TBG deficiency. Clin Endocrinol. 1997;47:vii–eight. [PubMed] [Google Scholar]
- Bartalena L, Robbins J. Variations in thyroid hormone transport proteins and their clinical implications. Thyroid. 1992;ii:237–245. [PubMed] [Google Scholar]
- Barter RE, Klaassen CD. Reduction of thyroid hormone levels and alteration of thyroid function by four representative UDP-glucuronyltransferase inducers in rats. Toxicol Appl Pharmacol. 1994;128:9–17. [PubMed] [Google Scholar]
- Beard AP, Rawlings NC. Thyroid role and furnishings on reproduction in ewes exposed to the organochlorine pesticides lindane or pentachlorophenol (PCP) from conception. J Toxicol Environ Wellness A. 1999;58:509–530. [PubMed] [Google Scholar]
- Beckett GJ, Arthur JR. Selenium and endocrine systems. J Endocrinol. 2005;184:455–465. [PubMed] [Google Scholar]
- Bianco Air-conditioning, Salvatore D, Gereben B, Berry MJ, Larsen PR. Biochemistry, cellular and molecular biology, and physiological roles of the iodothyronine selenodeiodinases. Endocr Rev. 2002;23:38–89. [PubMed] [Google Scholar]
- Chauhan KR, Kodavanti PR, McKinney JD. Assessing the function of ortho-substitution on polychlorinated biphenyl binding to transthyretin, a thyroxine transport protein. Toxicol Appl Pharmacol. 2000;162:ten–21. [PubMed] [Google Scholar]
- Cheek AO, Kow K, Chen J, McLachlan JA. Potential mechanisms of thyroid disruption in humans: interaction of organochlorine compounds with thyroid receptor, transthyretin, and thyroid-bounden globulin. Environ Health Perspect. 1999;107:273–278. [PMC free commodity] [PubMed] [Google Scholar]
- de Escobar GM, Obregon MJ, del Rey FE. Maternal thyroid hormones early in pregnancy and fetal brain development. All-time Pract Res Clin Endocrinol Metab. 2004;18:225–248. [PubMed] [Google Scholar]
- Donahue DA, Dougherty EJ, Meserve LA. Influence of a combination of two tetrachlorobiphenyl congeners (PCB 47; PCB 77) on thyroid condition, choline acetyltransferase (Chat) action, and short- and long-term retention in 30-24-hour interval-sometime Sprague-Dawley rats. Toxicology. 2004;203:99–107. [PubMed] [Google Scholar]
- Ellingsen DG, Efskind J, Haug E, Thomassen Y, Martinsen I, Gaarder PI. Effects of low mercury vapour exposure on the thyroid function in chloralkali workers. J Appl Toxicol. 2000;20:483–489. [PubMed] [Google Scholar]
- Forest JC, Masse J, Lane A. Evaluation of the analytical performance of the Boehringer Mannheim Elecsys 2010 immunoanalyzer. Clin Biochem. 1998;31:81–88. [PubMed] [Google Scholar]
- Goldey ES, Kehn LS, Lau C, Rehnberg GL, Crofton KM. Developmental exposure to polychlorinated biphenyls (Aroclor 1254) reduces circulating thyroid hormone concentrations and causes hearing deficits in rats. Toxicol Appl Pharmacol. 1995;135:77–88. [PubMed] [Google Scholar]
- Gould JC, Cooper KR, Scanes CG. Effects of polychlorinated biphenyls on thyroid hormones and liver blazon I monodeiodinase in the chick embryo. Ecotoxicol Environ Saf. 1999;43:195–203. [PubMed] [Google Scholar]
- Hagmar Fifty, Rylander Fifty, Dyremark E, Klasson-Wehler E, Erfurth EM. Plasma concentrations of persistent organochlorines in relation to thyrotropin and thyroid hormone levels in women. Int Curvation Occup Environ Health. 2001;74:184–188. [PubMed] [Google Scholar]
- Huang SA, Dorfman DM, Genest DR, Salvatore D, Larsen PR. Type 3 iodothyronine deiodinase is highly expressed in the homo uteroplacental unit and in fetal epithelium. J Clin Endocrinol Metab. 2003;88:1384–1388. [PubMed] [Google Scholar]
- Hume R, Simpson J, Delahunty C, van Toor H, Wu SY, Williams FL, et al. Homo fetal and string serum thyroid hormones: developmental trends and interrelationships. J Clin Endocrinol Metab 2004. 2004;89:4097–4103. [PubMed] [Google Scholar]
- Ijuin T, Douchi T, Yamamoto S, Ijuin Y, Nagata Y. The human relationship betwixt motherhood blues and thyroid dysfunction. J Obstet Gynaecol Res. 1998;24:49–55. [PubMed] [Google Scholar]
- Iwasaki T, Miyazaki W, Takeshita A, Kuroda Y, Koibuchi N. Polychlorinated biphenyls suppress thyroid hormone-induced transactivation. Biochem Biophys Res Commun. 2002;299:384–388. [PubMed] [Google Scholar]
- Jacobson JL, Jacobson SW. Association of prenatal exposure to an environmental contaminant with intellectual function in childhood. J Toxicol Clin Toxicol. 2002;xl:467–475. [PubMed] [Google Scholar]
- Jacobson JL, Jacobson SW. Prenatal exposure to polychlorinated biphenyls and attention at school historic period. J Pediatr. 2003;143:780–788. [PubMed] [Google Scholar]
- Khan MA, Hansen LG. Ortho-substituted polychlorinated biphenyl (PCB) congeners (95 or 101) subtract pituitary response to thyrotropin releasing hormone. Toxicol Lett. 2003;144:173–182. [PubMed] [Google Scholar]
- Kilby Physician, Verhaeg J, Gittoes Northward, Somerset DA, Clark PM, Franklyn JA. Circulating thyroid hormone concentrations and placental thyroid hormone receptor expression in normal human pregnancy and pregnancy complicated by intrauterine growth restriction (IUGR) J Clin Endocrinol Metab. 1998;83:2964–2971. [PubMed] [Google Scholar]
- Kleiman de Pisarev DL, Ríos de Molina MC, San Martín de Viale LC. Thyroid function and thyroxine metabolism in hexachlorobenzene-induced porphyria. Biochem Pharmacol. 1990;39:817–825. [PubMed] [Google Scholar]
- Koopman-Esseboom C, Morse DC, Weisglas-Kuperus Due north, Lutkeschipholt IJ, van der Paauw CG, Tuinstra LG, et al. Effects of dioxins and polychlorinated biphenyls on thyroid hormone status of pregnant women and their infants. Pediatr Res. 1994;36:468–473. [PubMed] [Google Scholar]
- LaFranchi SH, Haddow JE, Hollowell JG. Is thyroid inadequacy during gestation a risk factor for agin pregnancy and developmental outcomes? Thyroid. 2005;15:60–71. [PubMed] [Google Scholar]
- Lans MC, Spiertz C, Brouwer A, Koeman JH. Different competition of thyroxine bounden to transthyretin and thyroxine-binding globulin by hydroxy-PCBs, PCDDs and PCDFs. Eur J Pharmacol. 1994;270:129–136. [PubMed] [Google Scholar]
- Leonard JL, Köhrle J. 1996. Intracellular pathways of iodothyronine metabolism In: The Thyroid (Braverman LE, Utiger RD, eds). Philadelphia:Lippincott–Raven, 144–189.
- Longnecker MP, Wolff MS, Gladen BC, Brock JW, Grandjean P, Jacobson JL, et al. Comparison of polychlorinated biphenyl levels across studies of homo neurodevelopment. Environ Health Perspect. 2003;111:65–lxx. [PMC free article] [PubMed] [Google Scholar]
- Maia AL, Kieffer JD, Harney JW, Larsen PR. Effect of 3,five,iii′-triiodothyronine (T3) assistants on dio1 factor expression and T3 metabolism in normal and type 1 deiodinase-deficient mice. Endocrinology. 1995;136:4842–4849. [PubMed] [Google Scholar]
- McClain RM. Mechanistic considerations for the relevance of animal information on thyroid neoplasia to man risk assessment. Mutat Res. 1995;333:131–142. [PubMed] [Google Scholar]
- Meerts IA, Assink Y, Cenijn PH, Van Den Berg JH, Weijers BM, Bergman A, et al. Placental transfer of a hydroxylated polychlorinated biphenyl and furnishings on fetal and maternal thyroid hormone homeostasis in the rat. Toxicol Sci. 2002;68:361–371. [PubMed] [Google Scholar]
- Moorjani S, Dupont A, Labrie F, Lupien PJ, Brun D, Gagné C, et al. Increase in plasma loftier density lipoprotein concentration following complete androgen blockage in men with prostatic carcinoma. Metabolism. 1987;36:244–250. [PubMed] [Google Scholar]
- Oki N, Matsuo H, Nakago Due south, Murakoshi H, Laoag-Fernandez JB, Maruo T. Effects of 3,5,3′-triiodothyronine on the invasive potential and the expression of integrins and matrix metalloproteinases in cultured early placental extravillous trophoblasts. J Clin Endocrinol Metab. 2004;89:5213–5221. [PubMed] [Google Scholar]
- Osius N, Karmaus W, Kruse H, Witten J. Exposure to polychlorinated biphenyls and levels of thyroid hormones in children. Environ Health Perspect. 1999;107:843–849. [PMC free article] [PubMed] [Google Scholar]
- Pickard MR, Sinha AK, Ogilvie LM, Leonard AJ, Edwards PR, Ekins RP. Maternal hypothyroxinemia influences glucose transporter expression in fetal encephalon and placenta. J Endocrinol. 1999;163:385–394. [PubMed] [Google Scholar]
- Pilo A, Iervasi K, Vitek F, Ferdeghini M, Cazzuola F, Bianchi R. Thyroidal and peripheral production of 3,five,three′-triiodothyronine in humans by multicompartmental analysis. Am J Physiol. 1990;258:E715–E726. [PubMed] [Google Scholar]
- Popular VJ, Brouwers EP, Vader HL, Vulsma T, van Baar AL, de Vijlder JJ. Maternal hypothyroxinaemia during early pregnancy and subsequent child development: a 3-yr follow-up study. Clin Endocrinol (Oxf) 2003;59:282–288. [PubMed] [Google Scholar]
- Rathore M, Bhatnagar P, Mathur D, Saxena GN. Burden of organochlorine pesticides in claret and its effect on thyroid hormones in women. Sci Total Environ. 2002;295:207–215. [PubMed] [Google Scholar]
- Ribas-Fito Northward, Sala M, Cardo Eastward, Mazon C, De Muga ME, Verdu A, et al. Organochlorine compounds and concentrations of thyroid stimulating hormone in newborns. Occup Environ Med. 2003;60:301–303. [PMC costless article] [PubMed] [Google Scholar]
- Safety SH. Polychlorinated biphenyls (PCBs): environmental impact, biochemical and toxic responses, and implications for risk cess. Crit Rev Toxicol. 1994;24:87–149. [PubMed] [Google Scholar]
- Sandau CD, Ayotte P, Dewailly É, Duffe J, Norstrom RJ. Pentachlorophenol and hydroxylated polychlorinated biphenyl metabolites in umbilical cord plasma of neonates from coastal populations in Québec. Environ Health Perspect. 2002;110:411–417. [PMC free commodity] [PubMed] [Google Scholar]
- Santini F, Chiovato L, Ghirri P, Lapi P, Mammoli C, Montanelli L, et al. Serum iodothyronines in the human fetus and the newborn: testify for an of import part of placenta in fetal thyroid hormone homeostasis. J Clin Endocrinol Metab. 1999;84:493–498. [PubMed] [Google Scholar]
- Santini F, Chopra IJ, Hurd RE, Teco GN. A study of the characteristics of hepatic iodothyronine five′-monodeiodinase in various vertebrate species. Endocrinology. 1992;131:830–834. [PubMed] [Google Scholar]
- SAS Institute Inc 1999. SAS/STAT User'southward Guide. Version 8. Cary, NC:SAS Institute Inc.
- Schuur AG, Brouwer A, Bergman A, Coughtrie MW, Visser TJ. Inhibition of thyroid hormone sulfation by hydroxylated metabolites of polychlorinated biphenyls. Chem Biol Interact. 1998;109:293–297. [PubMed] [Google Scholar]
- Soechitram SD, Athanasiadou Thousand, Hovander 50, Bergman A, Sauer PJ. Fetal exposure to PCBs and their hydroxylated metabolites in a Dutch cohort. Environ Health Perspect. 2004;112:1208–1212. [PMC free article] [PubMed] [Google Scholar]
- Steuerwald U, Weihe P, Jorgensen PJ, Bjerve K, Brock J, Heinzow B, et al. Maternal seafood diet, methylmercury exposure, and neonatal neurologic function. J Pediatr. 2000;136:599–605. [PubMed] [Google Scholar]
- Tan TM, Sin YM, Wong KP. Mercury-induced UDP-glucuronyltransferase (UDPGT) activity in mouse kidney. Toxicology. 1990;64:81–87. [PubMed] [Google Scholar]
- Ulbrich B, Stahlmann R. Developmental toxicity of polychlorinated biphenyls (PCBs): a systematic review of experimental information. Arch Toxicol. 2004;78:252–268. [PubMed] [Google Scholar]
- Van Birgelen AP, Smit EA, Kampen IM, Groeneveld CN, Fase KM, Van der Kolk J, et al. Subchronic effects of ii,3,7,8-TCDD or PCBs on thyroid hormone metabolism: use in gamble assessment. Eur J Pharmacol. 1995;293:77–85. [PubMed] [Google Scholar]
- van Raaij JAGM, Kaptein East, Visser TJ, Van den Berg KJ. Increased glucuronidation of thyroid hormone in hexachlorobenzene-treated rats. Biochem Pharmacol. 1993;45:627–631. [PubMed] [Google Scholar]
- Vranckx R, Rouaze-Romet M, Savu L, Mechighel P, Maya M, Nunez EA. Regulation of rat thyroxine-binding globulin and transthyretin: studies in thyroidectomized and hypophysectomized rats given tri-iodothyronine or/and growth hormone. J Endocrinol. 1994;142:77–84. [PubMed] [Google Scholar]
- Vreugdenhil HJ, Lanting CI, Mulder PG, Boersma ER, Weisglas-Kuperus N. Furnishings of prenatal PCB and dioxin groundwork exposure on cerebral and motor abilities in Dutch children at school age. J Pediatr. 2002a;140:48–56. [PubMed] [Google Scholar]
- Vreugdenhil HJ, Mulder PG, Emmen HH, Weisglas-Kuperus N. Effects of perinatal exposure to PCBs on neuropsychological functions in the Rotterdam accomplice at 9 years of historic period. Neuropsychology. 2004;18:185–193. [PubMed] [Google Scholar]
- Vreugdenhil HJ, Slijper FM, Mulder PG, Weisglas-Kuperus N. Effects of perinatal exposure to PCBs and dioxins on play behavior in Dutch children at school age. Environ Wellness Perspect. 2002b;110:A593–A598. [PMC gratuitous article] [PubMed] [Google Scholar]
- Wade MG, Parent S, Finnson KW, Foster Westward, Younglai E, McMahon A, et al. Thyroid toxicity due to subchronic exposure to a complex mixture of sixteen organochlorines, lead, and cadmium. Toxicol Sci. 2002;67:207–218. [PubMed] [Google Scholar]
- Watanabe C, Yoshida K, Kasanuma Y, Kun Y, Satoh H. In utero methylmercury exposure differentially affects the activities of selenoenzymes in the fetal mouse brain. Environ Res. 1999;80:208–214. [PubMed] [Google Scholar]
- Winneke One thousand, Walkowiak J, Lilienthal H. PCB-induced neurodevelopmental toxicity in human infants and its potential mediation by endocrine dysfunction. Toxicology. 2002;181–182:161–165. [PubMed] [Google Scholar]
- Zoeller RT, Dowling AL, Vas AA. Developmental exposure to polychlorinated biphenyls exerts thyroid hormone-like effects on the expression of RC3/neurogranin and myelin basic poly peptide messenger ribonucleic acids in the developing rat brain. Endocrinology. 2000;141:181–189. [PubMed] [Google Scholar]
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