Pollutants Placenta Cord Blood Breast Milk

Advances in Autism Research
compiled by Teresa Binstock for
Autism Research Institute
April 2008

Pollutants in Placenta, Cord Blood, and Breast Milk of Humans

Many of the pollutants found in the placenta, cord blood, and breast milk of humans (6-31) are associated with autism (1-4). Other pollutants will contribute to a reduction in the levels of nutrients needed for detoxification (5). Global Community Monitor and Bucket Brigade provide assistance for detemining levels of pollutants in communities (32).

1. [mercury, cadmium, nickel, trichloroethylene, and vinyl chloride]

Autism spectrum disorders in relation to distribution of hazardous air pollutants in the san francisco bay area

Windham GC, Zhang L, Gunier R, Croen LA, Grether JK.
Environ Health Perspect. 2006 Sep;114(9):1438-44.
http://www.ehponline.org/members/2006/9120/9120.html

"The individual compounds that contributed most to these associations included mercury, cadmium, nickel, trichloroethylene, and vinyl chloride. CONCLUSIONS: Our results suggest a potential association between autism and estimated metal concentrations, and possibly solvents, in ambient air around the birth residence, requiring confirmation and more refined exposure assessment in future studies."
PMID: 16966102

2. [organochlorine pesticide applications]

Maternal residence near agricultural pesticide applications and autism spectrum disorders among children in the California Central Valley

Roberts EM, English PB, Grether JK, Windham GC, Somberg L, Wolff C.
Environ Health Perspect. 2007 Oct;115(10):1482-9.
http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=17938740

"Ambient levels of pesticides ("pesticide drift") are detectable at residences near agricultural field sites. OBJECTIVE: Our goal was to evaluate the hypothesis that maternal residence near agricultural pesticide applications during key periods of gestation could be associated with the development of autism spectrum disorders (ASD) in children... ASD risk increased with the poundage of organochlorine applied and decreased with distance from field sites."
PMID: 17938740

3. [Organophosphates detoxification and weak alleles of PON1]

Paraoxonase gene variants are associated with autism in North America, but not in Italy: possible regional specificity in gene-environment interactions

D'Amelio M et al.
Mol Psychiatry. 2005 Nov;10(11):1006-16.

Organophosphates (OPs) are routinely used as pesticides in agriculture and as insecticides within the household. Our prior work on Reelin and APOE delineated a gene-environment interactive model of autism pathogenesis, whereby genetically vulnerable individuals prenatally exposed to OPs during critical periods in neurodevelopment could undergo altered neuronal migration, resulting in an autistic syndrome. Since household use of OPs is far greater in the USA than in Italy, this model was predicted to hold validity in North America, but not in Europe. Here, we indirectly test this hypothesis by assessing linkage/association between autism and variants of the paraoxonase gene (PON1) encoding paraoxonase, the enzyme responsible for OP detoxification. Three functional single nucleotide polymorphisms, PON1 C-108T, L55M, and Q192R, were assessed in 177 Italian and 107 Caucasian-American complete trios with primary autistic probands. As predicted, Caucasian-American and not Italian families display a significant association between autism and PON1 variants less active in vitro on the OP diazinon (R192), according to case-control contrasts (Q192R: chi2=6.33, 1 df, P<0.025), transmission/disequilibrium tests (Q192R: TDT chi2=5.26, 1 df, P<0.025), family-based association tests (Q192R and L55M: FBAT Z=2.291 and 2.435 respectively, P<0.025), and haplotype-based association tests (L55/R192: HBAT Z=2.430, P<0.025). These results are consistent with our model and provide further support for the hypothesis that concurrent genetic vulnerability and environmental OP exposure may possibly contribute to autism pathogenesis in a sizable subgroup of North American individuals.
PMID: 16027737

4. Environmental mercury release, special education rates, and autism disorder: an ecological study of Texas

Palmer RF, Blanchard S, Stein Z, Mandell D, Miller C.
Health Place. 2006 Jun;12(2):203-9.
http://www.generationrescue.org/pdf/seed.pdf

The association between environmentally released mercury, special education and autism rates in Texas was investigated using data from the Texas Education Department and the United States Environmental Protection Agency. A Poisson regression analysis adjusted for school district population size, economic and demographic factors was used. There was a significant increase in the rates of special education students and autism rates associated with increases in environmentally released mercury. On average, for each 1,000 lb of environmentally released mercury, there was a 43% increase in the rate of special education services and a 61% increase in the rate of autism. The association between environmentally released mercury and special education rates were fully mediated by increased autism rates. This ecological study suggests the need for further research regarding the association between environmentally released mercury and developmental disorders such as autism. These results have implications for policy planning and cost analysis.
PMID: 16338635

5. Proximity to point sources of environmental mercury release as a predictor of autism prevalence

Palmer RF, Blanchard S, Wood R.
Health Place. 2008 Feb 12 [Epub ahead of print]

The objective of this study was to determine if proximity to sources of mercury pollution in 1998 were related to autism prevalence in 2002. Autism count data from the Texas Educational Agency and environmental mercury release data from the Environmental Protection Agency were used. We found that for every 1000 pounds of industrial release, there was a corresponding 2.6% increase in autism rates (p<.05) and a 3.7% increase associated with power plant emissions(P<.05). Distances to these sources were independent predictors after adjustment for relevant covariates. For every 10 miles from industrial or power plant sources, there was an associated decreased autism Incident Risk of 2.0% and 1.4%, respectively (p<.05). While design limitations preclude interpretation of individual risk, further investigations of environmental risks to child development issues are warranted.
PMID: 18353703

6. Autism, Pollution, and Nutrients: a Unifying Relationship
Teresa Binstock, April 2008
http://ravenintellections.com/autism-unifying.htm

7. Association of thyroid hormone concentrations with levels of organochlorine compounds in cord blood of neonates

Maervoet J et al.
Environ Health Perspect. 2007 Dec;115(12):1780-6.
http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=2137114&blobtype=pdf

BACKGROUND: Thyroid hormones are important regulators of brain development. During critical periods of development, even transient disorders in thyroid hormone availability may lead to profound neurologic impairment. Animal experiments have shown that certain environmental pollutants, including heavy metals and organochlorine compounds such as polychlorinated biphenyls (PCBs) and dioxins, can interfere with thyroid hormone homeostasis. Whether these contaminants can affect circulating levels of thyroid hormones in humans is unclear, however, because the results of available studies are inconsistent. OBJECTIVES: The aim of the present study is to examine the possible relationships between concentrations of environmental pollutants and thyroid hormone levels in human umbilical cord blood. METHODS: We measured concentrations of environmental pollutants [including selected PCBs, dioxin-like compounds, hexachlorobenzene, p,p'-DDE (dichlorodiphenyldichloroethylene), cadmium, lead] and thyroid hormones in the cord blood of 198 neonates. RESULTS: A statistically significant inverse relationship between concentrations of organochlorine compounds and levels of both free triiodothyronine (fT3) and free thyroxine (fT4), but not thyroid-stimulating hormone, was observed. We found no association between concentrations of heavy metals and thyroid hormone levels. CONCLUSIONS: Our results suggest that environmental chemicals may affect the thyroid system of human neonates. Although the differences in fT3 and fT4 levels associated with the organochlorine compounds were within the normal range, the observed interferences may still have detrimental effects on the neurologic development of the individual children, given the importance of thyroid hormones in brain development.
PMID: 18087600

8. Micronuclei in cord blood lymphocytes as a biomarker of transplacental exposure to environmental pollutants

Milosevic-Djordjevic O et al.
Tohoku J Exp Med. 2007 Nov;213(3):231-9.
http://www.jstage.jst.go.jp/article/tjem/213/3/231/_pdf

Exposure to environmental pollutants can result in chromosomal instability, which can produce a wide variety of effects on human health. In the spring of 1999, extensive environmental pollution happened in Kragujevac (the city in the central Serbia) with damages of soil, water and air, caused by the air strikes on "Zastava" complex. Because we found significant increase of micronuclei in newborns born 12 months after this environmental pollution (in the beginning of 2000), the purpose of the present study was to follow the frequency of micronuclei in lymphocytes of newborns born seven years after pollution (in 2006). The frequencies of micronuclei were estimated in cord blood lymphocytes of 41 newborns (20 males and 21 females) by application of cytokinesis-block (CB) micronucleus test. The obtained results showed that the mean value of micronuclei was significantly decreased in newborns born in 2006 in comparison to the mean value of micronuclei in newborns born 12 months after contamination (4.73 +/- 3.38 micronuclei/1,000 CB cells vs 9.36 +/- 5.60 micronuclei/1,000 CB cells), with probability p < 0.001. Newborn's gender, mother's age (19-40 years) and maternal cigarette smoking (< 20 cigarettes per day) did not show any noticeable effects on micronuclei frequencies in the analyzed newborns. There was relationship between the micronuclei frequencies and the level of environmental pollution (F = 6.95, p = 0.000). Our results suggest that the environment profoundly influences genetic constitution of newborns, and that micronucleus assay in cord blood lymphocytes is an important method for evaluation of transplacental mutagens.
PMID: 17984620

9. Hypoxemic fetoplacental vasoconstriction: a graduated response to reduced oxygen conditions in the human placenta

Ramasubramanian R et al.
Anesth Analg. 2006 Aug;103(2):439-42.
http://www.anesthesia-analgesia.org/cgi/content/full/103/2/439

We investigated the characteristics of hypoxemic fetoplacental vasoconstriction (HFPV) in the dual perfused, single isolated human placental cotyledon. Fetal arterial blood pressures (FAP) were measured in four cotyledons (Group 1) equilibrated with 21% oxygen (O2), 5% carbon dioxide (CO2), and nitrogen (N2) [control] followed by 5% CO2 in N2 for 30 min. FAP (mean +/- sd) increased from 69.8 (+/- 6.4) to 105 (+/- 3.0) mm Hg (P < 0.05), confirming the utility of HFPV in the human placenta. Eight more cotyledons (Group 2) were exposed sequentially and alternately at 15-min intervals to the control gases and to gas blends containing 15%, 12%, 5%, and 0% O2 with 5% CO2 and N2. FAP increased significantly (P < 0.05) in a stepwise fashion from 68.7 (+/- 3.7) to 70.5 (+/- 3.3) mm Hg with 15% O2; from 69.3 (+/- 3.8) to 72.4 (+/- 4.3) mm Hg with 12% O2; from 67.8 (+/- 3.2) to 74.5 (+/- 3.4) mm Hg with 5% O2; and from 69.7 (+/- 3.4) to 77.9 (+/- 5.9) mm Hg with 0% O2, suggesting that HFPV is a graduated response to reduced O2 conditions in the human placenta.
PMID: 16861430

10. Placental adaptive responses and fetal programming

Myatt L.
J Physiol. 2006 Apr 1;572(Pt 1):25-30. Epub 2006 Feb 9.
http://jp.physoc.org/cgi/content/full/572/1/25

Fetal programming occurs when the normal pattern of fetal development is disrupted by an abnormal stimulus or 'insult' applied at a critical point in in utero development. This then leads to an effect, for example diabetes or hypertension, which manifests itself in adult life. As the placenta is the regulator of nutrient composition and supply from mother to fetus and the source of hormonal signals that affect maternal and fetal metabolism, appropriate development of the placenta is crucial to normal fetal development. Placental function evolves in a carefully orchestrated developmental cascade throughout gestation. Disruption of this cascade can lead to abnormal development of the placental vasculature or of the trophoblast. Timing of a developmental 'insult' will be critical in consequent placental function and hence programming of the fetus. The 'insults' that alter placental development include hypoxia and abnormal maternal nutrient status, to which the placenta may adapt by alterations in transporter expression and activity to maintain fetal growth or by epigenetic regulation of placental gene expression. Hypoxia is physiological for organogenesis and placental tissue normally exists in a relatively hypoxic environment, but intrauterine growth restriction (IUGR) and pre-eclampsia are associated with a greater degree of trophoblast hypoxia. The metabolic activity of placental mitochondria leads to oxidative stress even in normal pregnancy which is exacerbated further in IUGR, diabetic and pre-eclamptic pregnancies and may also give nitrative stress known to lead to covalent modification and hence altered activity of proteins. Hypoxia, oxidative and nitrative stress all alter placenta development and may be a general underlying mechanism that links altered placental function to fetal programming.
PMID: 16469781

11. Distribution of PCDDs/PCDFs and Co-PCBs in human maternal blood, cord blood, placenta, milk, and adipose tissue: dioxins showing high toxic equivalency factor accumulate in the placenta

Suzuki G, Nakano M, Nakano S.
Biosci Biotechnol Biochem. 2005 Oct;69(10):1836-47.
http://www.jstage.jst.go.jp/article/bbb/69/10/1836/_pdf

To assess levels of dioxin background contamination and transfer of dioxins from mothers to unborn children and infants, concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and coplanar-polychlorinated biphenyls (Co-PCBs) were measured in human samples from expectant and nursing mothers living in Nara, Japan. The average toxic equivalency quantities (TEQs) of PCDDs/PCDFs and Co-PCBs from circulating maternal blood, cord blood, placenta, milk taken 3-10 d after delivery, milk taken one month after delivery, and adipose tissue were 26 and 9.3, 15 and 2.3, 31 and 1.2, 16 and 5.4, 18 and 8.8, and 16 and 7.7 pg-TEQ/g-fat, respectively. Among the various PCDD/PCDF congeners, 1,2,3,7,8-PeCDD and 2,3,4,7,8-PeCDF contributed most heavily to the TEQs of all maternal samples. Among the various Co-PCB congeners, 3,3',4,4',5-PeCB (#126), 2,3,3',4,4',5-HxCB (#156), and 2,3',4,4',5-PeCB (#118) contributed most heavily to the TEQs of all maternal samples. But, the concentrations and relative percentages of congeners differed among the various samples, suggesting that congeners showing high toxic equivalency factor accumulate in the placenta.
PMID: 16244432

12. Air pollution and lymphocyte phenotype proportions in cord blood

Hertz-Picciotto I et al.
Environ Health Perspect. 2005 Oct;113(10):1391-8.
http://www.ehponline.org/members/2005/7610/7610.html

Effects of air pollution on morbidity and mortality may be mediated by alterations in immune competence. In this study we examined short-term associations of air pollution exposures with lymphocyte immunophenotypes in cord blood among 1,397 deliveries in two districts of the Czech Republic. We measured fine particulate matter < 2.5 microm in diameter (PM2.5) and 12 polycyclic aromatic hydrocarbons (PAHs) in 24-hr samples collected by versatile air pollution samplers. Cord blood samples were analyzed using a FACSort flow cytometer to determine phenotypes of CD3+ T-lymphocytes and their subsets CD4+ and CD8+, CD19+ B-lymphocytes, and natural killer cells. The mothers were interviewed regarding sociodemographic and lifestyle factors, and medical records were abstracted for obstetric, labor and delivery characteristics. During the period 1994 to 1998, the mean daily ambient concentration of PM2.5 was 24.8 microg/m3 and that of PAHs was 63.5 ng/m3. In multiple linear regression models adjusted for temperature, season, and other covariates, average PAH or PM2.5 levels during the 14 days before birth were associated with decreases in T-lymphocyte phenotype fractions (i.e., CD3+ CD4+, and CD8+), and a clear increase in the B-lymphocyte (CD19+) fraction. For a 100-ng/m3 increase in PAHs, which represented approximately two standard deviations, the percentage decrease was -3.3% [95% confidence interval (CI), -5.6 to -1.0%] for CD3+, -3.1% (95% CI, -4.9 to -1.3%) for CD4+, and -1.0% (95% CI, -1.8 to -0.2%) for CD8+ cells. The corresponding increase in the CD19+ cell proportion was 1.7% (95% CI, 0.4 to 3.0%). Associations were similar but slightly weaker for PM2.5. Ambient air pollution may influence the relative distribution of lymphocyte immunophenotypes of the fetus.
PMID: 16203253

13. Cadmium reduces 11 beta-hydroxysteroid dehydrogenase type 2 activity and expression in human placental trophoblast cells

Yang K et al.
Am J Physiol Endocrinol Metab. 2006 Jan;290(1):E135-E142. Epub 2005 Sep 6.
http://ajpendo.physiology.org/cgi/content/full/290/1/E135

Cadmium, a common environmental pollutant and a major constituent of tobacco smoke, has been identified as a new class of endocrine disruptors with a wide range of detrimental effects on mammalian reproduction. During human pregnancy, maternal cadmium exposure, via the environment and/or cigarette smoking, leads to fetal growth restriction (FGR), but the underlying mechanisms are unknown. Although a substantial amount of evidence suggests that cadmium may affect fetal growth indirectly via the placenta, the molecular targets remain to be identified. Given that reduced placental 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta-HSD2, encoded by HSD11B2 gene) is causally linked to FGR, the present study was undertaken to examine the hypothesis that cadmium induces FGR in part by targeting placental HSD11B2. Using cultured human trophoblast cells as a model system, we showed that cadmium exposure resulted in a time- and concentration-dependent decrease in 11 beta-HSD2 activity, such that an 80% reduction was observed after 24-h treatment at 1 microM. It also led to a similar decrease in levels of 11 beta-HSD2 protein and mRNA, suggesting that cadmium reduced 11 beta-HSD2 expression. Furthermore, cadmium diminished HSD11B2 promoter activity, indicative of repression of HSD11B2 gene transcription. In addition, the effect of cadmium was highly specific, in that other divalent metals (Zn(2+), Mg(2+), and Mn(2+)) as well as nicotine and cotinine (a major metabolite of nicotine) did not alter 11 beta-HSD2 activity. Taken together, these findings demonstrate that cadmium reduces human placental 11 beta-HSD2 expression and activity by suppressing HSD11B2 gene transcription. Thus the present study identifies placental 11 beta-HSD2 as a novel molecular target of cadmium. It also reveals a molecular mechanism by which this endocrine disruptor may affect human placental function and, consequently, fetal growth and development.
PMID: 16144812

14. Trialkyltin compounds bind retinoid X receptor to alter human placental endocrine functions

Nakanishi T et al.
Mol Endocrinol. 2005 Oct;19(10):2502-16. Epub 2005 Jun 7.
http://mend.endojournals.org/cgi/content/full/19/10/2502

Retinoid X receptor (RXR) is a nuclear receptor that plays important and multiple roles in mammalian development and homeostasis. We previously reported that, in human choriocarcinoma cells, tributyltin chloride and triphenyltin hydroxide, which are typical environmental contaminants and cause masculinization in female mollusks, are potent stimulators of human chorionic gonadotropin production and aromatase activity, which play key endocrine functions in maintaining pregnancy and fetal development. However, the molecular mechanism through which these compounds stimulate these endocrine functions remains unclear. Our current study shows that trialkyltin compounds, including tributyltin chloride and triphenyltin hydroxide, function as RXR agonists. Trialkyltins directly bind to the ligand-binding domain of RXR with high affinity and function as transcriptional activators. Unlike the natural RXR ligand, 9-cis-retinoic acid, the activity of trialkyltins is RXR specific and does not activate the retinoic acid receptor pathway. In addition, trialkyltins activate RXR to stimulate the expression of a luciferase reporter gene containing the human placental promoter I.1 sequence of aromatase, suggesting that trialkyltins stimulate human placental endocrine functions through RXR-dependent signaling pathways. Therefore, our results suggest that activation of RXR may be a novel mechanism by which trialkyltins alter human endocrine functions.
PMID: 15941851

15. Differential effects of glyphosate and roundup on human placental cells and aromatase

Richard S et al.
Environ Health Perspect. 2005 Jun;113(6):716-20.
http://www.ehponline.org/members/2005/7728/7728.html

Roundup is a glyphosate-based herbicide used worldwide, including on most genetically modified plants that have been designed to tolerate it. Its residues may thus enter the food chain, and glyphosate is found as a contaminant in rivers. Some agricultural workers using glyphosate have pregnancy problems, but its mechanism of action in mammals is questioned. Here we show that glyphosate is toxic to human placental JEG3 cells within 18 hr with concentrations lower than those found with agricultural use, and this effect increases with concentration and time or in the presence of Roundup adjuvants. Surprisingly, Roundup is always more toxic than its active ingredient. We tested the effects of glyphosate and Roundup at lower nontoxic concentrations on aromatase, the enzyme responsible for estrogen synthesis. The glyphosate-based herbicide disrupts aromatase activity and mRNA levels and interacts with the active site of the purified enzyme, but the effects of glyphosate are facilitated by the Roundup formulation in microsomes or in cell culture. We conclude that endocrine and toxic effects of Roundup, not just glyphosate, can be observed in mammals. We suggest that the presence of Roundup adjuvants enhances glyphosate bioavailability and/or bioaccumulation.
PMID: 15929894

16. Pyruvate kinase activity in the placentas of women living in polluted and unpolluted environments

Kedryna T, Gumińska M, Lucyna Z.
Med Sci Monit. 2004 Dec;10(12):CR672-8.

BACKGROUND: It was shown earlier that in women living in a polluted environment, the proportion of hypotrophic newborns was greater than in the general population. The placentas of these women show significant histological changes. The authors decided to check whether the activity of pyruvate kinase (PK), a key enzyme in the third stage of glycolysis, changes similarly. MATERIAL/METHODS: The study was conducted on placentas collected from women who had lived in a polluted environment (Groups I and II) and those who had inhabited an unpolluted area (Group III) while pregnant. RESULTS: Total PK activity and the specific activities of its isoenzymes were measured according to the Bücher and Pfleiderer method. The isolation of PK isoenzymes was carried out following the previously described procedure. Total PK activity was lower in the placentas of women of Groups I and II than in those of Group III. The presence of two PK isoenzymes, M2 and L, was demonstrated. The M2 and L isoenzymes from the placentas of Groups I and II had a lower specific activity than those of Group III. Only one form of the M2 isoenzyme and the L dephospho-isoenzyme in the placentas from Groups I and II was observed, while in placentas of Group III women both forms of the M2 isoenzyme and the L phospho-isoenzyme were noted. CONCLUSIONS: It is possible that the presence of the two PK isoenzymes in the placenta ensures the production of a sufficient amount of pyruvate.
PMID: 15567985

17. A revised probabilistic estimate of the maternal methyl mercury intake dose corresponding to a measured cord blood mercury concentration

Stern AH.
Environ Health Perspect. 2005 Feb;113(2):155-63.
http://www.ehponline.org/members/2004/7417/7417.html

In 2001, the U.S. Environmental Protection Agency (EPA) adopted a revised reference dose (RfD) for methyl mercury (MeHg) of 0.1 microg/kg/day. The RfD is based on neurologic developmental effects measured in children associated with exposure in utero to MeHg from the maternal diet. The RfD derivation proceeded from a point of departure based on measured concentration of mercury in fetal cord blood (micrograms per liter). The RfD, however, is a maternal dose (micrograms per kilogram per day). Reconstruction of the maternal dose corresponding to this cord blood concentration, including the variability around this estimate, is a critical step in the RfD derivation. The dose reconstruction employed by the U.S. EPA using the one-compartment pharmacokinetic model contains two areas of significant uncertainty: It does not directly account for the influence of the ratio of cord blood: maternal blood Hg concentration, and it does not resolve uncertainty regarding the most appropriate central tendency estimates for pregnancy and third-trimester-specific model parameters. A probabilistic reassessment of this dose reconstruction was undertaken to address these areas of uncertainty and generally to reconsider the specification of model input parameters. On the basis of a thorough review of the literature and recalculation of the one-compartment model including sensitivity analyses, I estimated that the 95th and 99th percentiles (i.e., the lower 5th and 1st percentiles) of the maternal intake dose corresponding to a fetal cord blood Hg concentration of 58 microg/L are 0.3 and 0.2 microg/kg/day, respectively. For the 99th percentile, this is half the value previously estimated by the U.S. EPA.
PMID: 15687052

18. Comparison of accumulation and altered steroid secretion by placental tissue treated with TCDD and natural mixture of PCDDs-PCDFs

Augustowska K et al.
Reproduction. 2003 Nov;126(5):681-7.
http://www.reproduction-online.org/cgi/reprint/126/5/681

Explants of human placental tissue harvested immediately after expulsion were used to determine differences between accumulation of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and polychlorinated dibenzo-p-dioxin (PCDD)-polychlorinated dibenzo-p-furans (PCDF) environmental mixture, and their influence on placental steroidogenesis. Explants were cultured in vitro for 5 days in media supplemented each day with either TCDD or a mixture of PCDD-PCDF. Media were collected every day for steroid content analysis by radioimmunoassay. At 24 h after the last treatment, the tissue was frozen for further analysis of the content of TCDD or other congeners present in the mixture. Determinations of TCDD and all 17 PCDDs and PCDFs were performed using gas chromatography equipped with DB-5 MS and DB-17 capillary columns. In the control tissue, the amounts of both TCDD and mixture components were close to the limit of detection of the method. In the treated tissue, the TCDD accumulation was 94% of the total exposure to TCDD. The most toxic congeners 2,3,7,8-TCDD, 2,3,7,8-tetrachlorodibenzofuran, 1,2,3,7,8-pentachlorodibenzo-p-dioxin (PeCDD), 1,2,3,7,8-pentachlorodibenzo-p-furans (PeCDF) and 2,3,4,7,8-PeCDF showed the highest accumulation, which covered >50% of the total toxic equivalents present in this mixture. During the first 3 days of exposure to TCDD there was no effect on the conversion of dehydroepiandrosterone to oestradiol, whereas on days 4 and 5 of exposure, a twofold decrease in oestradiol secretion was observed. However, a small but significant increase in oestradiol secretion was noted at all times of exposure to the PCDD-PCDF mixture. All observed changes in oestradiol secretion were not accompanied by changes in progesterone secretion after exposure to TCDD or the PCDD-PCDF mixture. In conclusion, a high accumulation of TCDD in the placental tissue resulted in a decrease in oestradiol secretion and in vivo this could result in a decrease in blood flow through the placenta. From the mixture, PeCDD and PeCDF in the higher amount accumulated in the placental tissue caused an increase in oestrogen secretion and as a consequence could activate oxytocin secretion from the pituitary and early pregnancy outcome.
PMID: 14611642

19. [Drinking water]

Bromodichloromethane inhibits human placental trophoblast differentiation

Chen J et al.
Toxicol Sci. 2004 Mar;78(1):166-74. Epub 2003 Dec 22.
http://toxsci.oxfordjournals.org/cgi/content/full/78/1/166

Epidemiological data suggest an association between exposures to bromodichloromethane (BDCM), a trihalomethane found in drinking water as a result of drinking water disinfection, and an increased risk of spontaneous abortion. We previously hypothesized that BDCM targets the placenta and showed that the secretion of chorionic gonadotrophin (CG) was reduced in primary cultures of human term syncytiotrophoblasts exposed to BDCM. In the present study we extend this observation by evaluating the effects of BDCM on the morphological differentiation of mononucleated cytotrophoblast cells to multinucleated syncytiotrophoblast-like colonies. Addition of BDCM to cytotrophoblast cultures inhibited the subsequent formation of multinucleated colonies in a dose-dependent manner, as determined by immunocytochemical staining for desmosomes and nuclei. The effect was seen at BDCM concentrations between 0.02 and 2 mM and was confirmed by quantitative image analysis. Secretion of bioactive and immunoreactive chorionic gonadotropin was also significantly inhibited in a dose-dependent manner under these culture conditions, and cellular levels of CG were also reduced. Trophoblast viability was not compromised by exposure to BDCM. We conclude that BDCM disrupts syncytiotrophoblast formation and inhibits CG secretion in vitro. Although other tissue targets are not ruled out, these data substantiate the idea that BDCM targets the placenta and could have implications for understanding the adverse pregnancy outcomes associated with BDCM exposure in humans.
PMID: 14691210

20. In vitro activation of cord blood mononuclear cells and cytokine production in a remote coastal population exposed to organochlorines and methyl mercury

Bilrha H et al.
Environ Health Perspect. 2003 Dec;111(16):1952-7.
http://www.ehponline.org/members/2003/6433/6433.html

Remote coastal populations that rely on seafood for subsistence often receive unusually high doses of organochlorines and methyl mercury. Immunosuppression resulting from prenatal exposure to organochlorines has been reported in wildlife species and humans. In this study, we assessed lymphocyte activation and associated cytokine secretion in 47 newborns from a remote maritime population living on the Mid and Lower North Shore regions of the St. Lawrence River (Québec, Canada; subsistence fishing group) and 65 newborns from nearby urban settings (reference group). Cord blood samples were collected for organochlorine and mercury analyses and also to isolate cord blood mononuclear cells (CBMCs) for the in vitro assessment of cytokine production and expression of surface markers after mitogenic stimulation (CD4(+)CD45RO(+), CD8(+)CD45RO(+), CD3(+)CD25(+), and CD8(+)HLA-DR(+)). Blood mercury and plasma concentrations of polychlorinated biphenyls (PCBs), 1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene (p,p'-DDE), and hexachlorobenzene (HCB) were significantly higher in the subsistence fishing group than in the reference group (p < 0.001). No difference was observed between the two groups regarding subsets of lymphocytes showing markers of activation. In vitro secretion of cytokines by CBMCs after mitogenic stimulation was lower in the subsistence fishing group than in the reference group (p < 0.05). Moreover, we found an inverse correlation between tumor necrosis factor-alpha (TNF-alpha) secretion and plasma PCB, p,p'-DDE, and HCB concentrations (p < 0.05). Our data support a negative association between TNF-alpha secretion by CBMCs and prenatal organochlorine exposure. If the relationship between organochlorine and TNF-alpha secretion is causal, it would suggest a role for this important proinflammatory cytokine in mediating organochlorine-induced immunotoxicity in infants developmentally exposed to these compounds.
PMID: 14644672

21. [drinking water]

Effect of bromodichloromethane on chorionic gonadotrophin secretion by human placental trophoblast cultures

Chen J et al.
Toxicol Sci. 2003 Nov;76(1):75-82. Epub 2003 Sep 11.
http://toxsci.oxfordjournals.org/cgi/content/full/76/1/75

Bromodichloromethane (BDCM) is a trihalomethane found in drinking water as a by-product of disinfection processes. BDCM is hepatotoxic and nephrotoxic in rodents and has been reported to cause strain-specific full-litter resorption in F344 rats during the luteinizing hormone-dependent phase of pregnancy. In humans, epidemiological studies suggest an association between exposure to BDCM in drinking water and increased risk of spontaneous abortion. To begin to address the mechanism(s) of BDCM-induced spontaneous abortion, we hypothesized that BDCM targets the placenta. Primary cultures of human term trophoblast cells were used as an in vitro model to test this hypothesis. Trophoblasts were allowed to differentiate into multinucleated syncytiotrophoblast-like colonies, after which they were incubated for 24 h with different concentrations of BDCM (20 nM to 2 mM). Culture media were collected and assayed for immunoreactive and bioactive chorionic gonadotropin (CG). Cultures exposed to BDCM showed a dose-dependent decrease in the secretion of immunoreactive CG as well as bioactive CG. The lowest effective BDCM concentration was 20 nM, approximately 35-times higher than the maximum concentration reported in human blood (0.57 nM). Trophoblast morphology and viability were similar in controls and cultures exposed to BDCM. We conclude that BDCM perturbs CG secretion by differentiated trophoblasts in vitro. This suggests that the placenta is a likely target of BDCM toxicity in the human and that this could be related to the adverse pregnancy outcomes associated with BDCM.
PMID: 12970577

22. Effects of low concentrations of organochlorine compounds in women on calcium transfer in human placental syncytiotrophoblast

Hamel A et al.
Toxicol Sci. 2003 Nov;76(1):182-9. Epub 2003 Sep 11.
http://toxsci.oxfordjournals.org/cgi/content/full/76/1/182

For most Canadians, food represents one of the major sources of environmental contaminants. Among them, organochlorine compounds (OCs) are known to affect calcium (Ca2+) homeostasis. They are neurotoxic by perturbation of Ca2+ channels and pumps, and they interfere with protein kinase C (PKC) and Ca2+ binding protein (CaBP). Ca2+ is an essential element to adequate fetal growth and development. The aim of the present study is to determine the relation between low environmental maternal exposure to OCs, such as polychlorinated biphenyls (PCB 153), Aroclor 1260, p,p'-dichlorodiphenyltrichloroethane (DDT) and p,p'-dichlorodiphenyl-dichloroethane (DDE), Ca2+ levels in serum and placenta, placental Ca2+ transfer, and newborn development. Total Ca2+ and OCs were measured in women's serum samples, as well as in umbilical cord's serum and placenta at term. Placentas were taken for trophoblast cells isolation and Ca2+ incorporation kinetic experiments. Our results were obtained from 30 pregnant women from the southwestern area of Quebec. Concentrations of Aroclor 1260, PCB 153, DDE, and DDT were respectively 6.1, 6.0, 3.1, and 2.9 times lower in the umbilical cord serum than in the mother's serum at term. In the placenta, DDE was accumulated at higher levels than other contaminants. A tendency towards an inverse relation was observed for in OCs found in three compartments and Ca2+ levels in maternal serum and in placental tissues. Maternal Ca2+ concentrations do not influence Ca2+ uptake by syncytiotrophoblast. Only DDE (>/=0.70 mug/l) in maternal serum significantly was associated with a small increase in Ca2+ uptake by syncytiotrophoblast. This study will help us determine if low OC contamination significantly modifies Ca2+ transfer in syncytiotrophoblast.
PMID: 12970576

23. An assessment of the cord blood:maternal blood methylmercury ratio: implications for risk assessment

Stern AH, Smith AE.
Environ Health Perspect. 2003 Sep;111(12):1465-70.
http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1241648&blobtype=pdf

In the current U.S. Environmental Protection Agency reference dose (RfD) for methylmercury, the one-compartment pharmacokinetic model is used to convert fetal cord blood mercury (Hg) concentration to a maternal intake dose. This requires a ratio relating cord blood Hg concentration to maternal blood Hg concentration. No formal analysis of either the central tendency or variability of this ratio has been done. This variability contributes to the overall variability in the dose estimate. A ratio of 1.0 is implicitly used in the model, but an uncertainty factor adjustment is applied to the central tendency estimate of dose to address variability in that estimate. Thus, incorporation of the cord:maternal ratio and its variability into the estimate of intake dose could result in a significant change in the value of the RfD. We analyzed studies providing data on the cord:maternal blood Hg ratio and conducted a Monte Carlo-based meta-analysis of 10 studies meeting all inclusion criteria to generate a comprehensive estimate of the central tendency and variability of the ratio. This analysis results in a recommended central tendency estimate of 1.7, a coefficient of variation of 0.56, and a 95th percentile of 3.4. By analogy to the impact of the similar hair:blood Hg ratio on the overall variability in the dose estimate, incorporation of the cord:maternal ratio may support a 3-fold uncertainty factor adjustment to the central tendency estimate of dose to account for pharmacokinetic variability. Whether the information generated in this analysis is sufficient to warrant a revision to the RfD will depend on the outcome of a comprehensive reanalysis of the entire one-compartment model. We are currently engaged in such an analysis.
PMID: 12948885

24. Effects of dioxin (2,3,7,8-TCDD) and PCDDs/PCDFs congeners mixture on steroidogenesis in human placenta tissue culture

Augustowska K et al.
Endocr Regul. 2003 Mar;37(1):11-9.
http://tinyurl.com/6fa2uy

OBJECTIVE: The aim was to compare the direct effect of most toxic 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as well as of naturally occurring congener mixture of polychlorinated dibenzodioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) extracted from fly ash on the placental steroidogenesis. The concentration of all 17 toxic congeners was reported and the toxic equivalent (TEQ) was calculated as a 27.7 micrograms-TEQ/kg of fly ash. METHODS: Placental cotyledons were harvested immediately after expulsion of placenta. The cells were prepared according to KLIMAN et al. (1986). To examine TCDD and PCDDs/PCDFs mixture action on cytochrome P450 side change cleavage enzyme (P450 scc) and 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) activity the placental cells were cultured either in basal conditions or with the addition of 25-hydroxycholesterol (25-OH) or pregnenolone (P5). RESULTS: TCDD in all doses used decreased basal P4 secretion, while did not show any effect on 25-hydroxycholesterol (25-OH) and pregnenolone (P5) supplemented cultures. In all variants of culture PCDDs/PCDFs mixture was without effect on basal and substrate supplemented progesterone (P4) secretion suggesting a reduction in the activity of cytochrome P450scc or 3 beta-HSD. To examine TCDD and PCDDs/PCDFs mixture action on aromatase cytochrom P450 (P450 arom) activity the placental cells were cultured in basal condition or with the addition of dehydroepi-androsterone (DHEA) or testosterone (T). Significant increase of estradiol secretion under the influence of TCDD in DHEA and T supplemented cultures suggests its action on the activity of P450 arom. CONCLUSION: The discrepancy found between the action of pure TCDD and dioxin mixture on placental steroids secretion is possibly due to an additional effect of pentachlorodibenzo-p-dioxin (PeCDD) and pentachlorodibenzo-furan (PeCDF) which covered > 50% of the total toxic equivalents (TEQ) present in this mixture.
PMID: 12916318

25. Parent bisphenol A accumulation in the human maternal-fetal-placental unit

Schönfelder G et al.
Environ Health Perspect. 2002 Nov;110(11):A703-7.
http://www.ehponline.org/members/2002/110pA703-A707schonfelder/schonfelder-full.html

Bisphenol A (BPA), an endocrine disruptor, is employed in the manufacture of a wide range of consumer products. The suggestion that BPA, at amounts to which we are exposed, alters the reproductive organs of developing rodents has caused concern. At present, no information exists concerning the exposure of human pregnant women and their fetuses to BPA. We therefore investigated blood samples from mothers (n = 37) between weeks 32 and 41 of gestation. Afer the births, we also analyzed placental tissue and umbilical cord blood from the same subjects. We developed a novel chemical derivatization-gas chromatography/mass spectrometry method to analyze parent BPA at concentrations < 1 micro g/mL in plasma and tissues. Concentrations of BPA ranged from 0.3 to 18.9 ng/mL (median = 3.1 ng/mL) in maternal plasma, from 0.2 to 9.2 ng/mL (median = 2.3 ng/mL) in fetal plasma, and from 1.0 to 104.9 ng/g (median = 12.7 ng/g) in placental tissue. BPA blood concentrations were higher in male than in female fetuses. Here we demonstrate parent BPA in pregnant women and their fetuses. Exposure levels of parent BPA were found within a range typical of those used in recent animal studies and were shown to be toxic to reproductive organs of male and female offspring. We suggest that the range of BPA concentrations we measured may be related to sex differences in metabolization of parent BPA or variable maternal use of consumer products leaching BPA.
PMID: 12417499

26. Temporal trends of organochlorine concentrations in umbilical cord blood of newborns from the lower north shore of the St. Lawrence river (Québec, Canada)

Dallaire F et al.
Environ Health Perspect. 2002 Aug;110(8):835-8.
http://www.ehponline.org/members/2002/110p835-838dallaire/dallaire-full.html

This study describes the time trends of organochlorines [OCs; 14 polychlorinated biphenyls (PCBs) and 11 chlorinated pesticides] in umbilical cord plasma of newborns in a remote Canadian coastal population. We analyzed 408 cord blood samples collected between 1993 and 2000 for PCBs, chlordanes, dichlorodiphenyltrichloroethane (DDT), dichlorodiphenyltrichloroethylene (DDE), hexachlorobenzene (HCB), and n-3 fatty acids. We also gathered information on the mothers (age, past and present residence, ethnic group, use of tobacco during pregnancy, and breast-feeding during previous pregnancies). From 1993 to 2000, mean concentrations of PCBs, chlordanes, DDT/DDE, and HCB in cord blood decreased by 63%, 25%, 66%, and 69%, respectively (p < 0.0001). Multiple regression analysis with the year of birth as the main independent variable yielded a strong significant exponential decrease for all contaminants (in all age and ethnic groups). We detected no monthly or seasonal pattern. We used n-3 fatty acids concentration as a surrogate of maternal fish consumption. Fish consumption declined only slightly between 1993 and 2000, but this decrease did not contribute significantly to the reduction of OCs. These results show that prenatal exposure to persistent OCs has declined significantly between 1993 and 2000 in this population.
PMID: 12153768

27. Lactate dehydrogenase activity in human placenta following exposure to environmental pollutants

Kaiglová A, Reichrtová E, Adamcáková A, Wsólová L.
Physiol Res. 2001;50(5):525-8.
http://www.biomed.cas.cz/physiolres/pdf/50/50_525.pdf

The impact of environmental pollution at the place of residence of pregnant women and of their smoking habits on the cellular energy metabolism of placental tissue was investigated. Samples of full-term placentas were randomly collected from two environmentally different regions of Slovakia (Bratislava, Stará Lubovna) and the activity of lactate dehydrogenase (LDH) was measured. Our results showed enhanced LDH activity in the placenta that was dependent on both the type of environmental pollutants at the place of residence and the smoking habits during pregnancy. The enhanced LDH activity may reflect hypoxic conditions due to the accumulation of heavy metals and toxic compounds of tobacco smoke in the placental tissue. A high content of heavy metal particles, found in placental samples from Stará Lubovna in our previous studies, might contribute to the increased LDH activity in placentas from this region. We hypothesize that fine metal particles deposited in the placental tissue might be phagocytozed by the syncytiotrophoblast, thus contributing to the decreased oxygen level in placental tissue.
PMID: 11702858

28. The Tagum study I: analysis and clinical correlates of mercury in maternal and cord blood, breast milk, meconium, and infants' hair

Ramirez GB et al.
Pediatrics. 2000 Oct;106(4):774-81.
http://pediatrics.aappublications.org/cgi/content/full/106/4/774

OBJECTIVES: To compare the indicators and levels of mercury (Hg) exposure in the mother with those in the fetal compartments, and determine its effects on the newborn. METHODS: Hg levels using atomic absorption spectrophotometry were determined in maternal blood, breast milk, cord blood, infants' hair, and meconium of 78 consecutive mother-infant pairs in a community with high Hg pollution. The prevalence and levels of Hg both in meconium and in cord blood were correlated with maternal and infant risk factors. RESULTS: The prevalence of Hg in the fetal compartments was higher than in the maternal fluid compartments. Hg was present in 6.4% of maternal blood and 6.4% of breast milk, as compared with 16.7% of cord blood, 31.6% of infants' hair, and 46.1% of meconium. Forty-six percent of infants with Hg in cord blood had none in meconium, whereas 80.6% with Hg in meconium had none in cord blood. Hg was not present in the maternal blood of all infants (n = 36) with Hg in their meconium. Among those with detectable Hg, the mean levels were: mothers' blood 24 parts per billion +/- 5.47, cord blood 53.3 parts per billion +/- 37.49, and meconium 48.6 +/- 43.48. Quantitative measurement in hair was not done because of insufficient sample. Paired comparisons were all significant between Hg levels in the mothers' blood and meconium, mothers' blood and cord blood, and cord blood and meconium. Regression analysis showed Hg levels in meconium to be correlated with prevalence of Hg in infants' hair, length of stay in Tagum, and meconium-stained amniotic fluid. Fisher's Exact probability test showed that the prevalence of Hg in meconium was significantly related to the prevalence of Hg in the mothers' blood and length of stay in Tagum. The prevalence of Hg in cord blood was significantly related to the prevalence in the mothers' blood. Regression analysis of levels of Hg in cord blood showed a significant relation to levels in mothers' blood (.0001), prevalence in infants' hair (.0126), gestational age (GA) (.0091), and head circumference (HC) (.0469). By quadrant analysis of weight against HC in 66 full-term infants all of 4 infants weighing an average of >3000 g at birth and with HCs lower than the fifth percentile had Hg in meconium. CONCLUSION: The higher prevalence and levels of Hg in the fetal compartments reflect the ease of placental transfer with fetal trapping. Hg determinations in the mothers' blood underestimate the degree and extent of fetal exposure. There is a significant difference in each compartment's ability to reflect Hg exposure of the fetus. A small HC may be associated with the presence of Hg in meconium. Hg in meconium should be measured in addition to cord blood to determine the load of fetal Hg.
PMID: 11015522

29. Cord serum immunoglobulin E related to the environmental contamination of human placentas with organochlorine compounds

Reichrtová E et al.
Environ Health Perspect. 1999 Nov;107(11):895-9.
http://www.ehponline.org/members/1999/107p895-899reichrtova/reichrtova-full.html

Allergic diseases are on the rise in both prevalence and severity, especially in industrialized countries. The process of allergic sensitization needs an understanding of the role environmental factors play in its development. In addition to traditionally considered air pollutants, various persistent organochlorine pollutants, which accumulate in the human body over a lifetime via food intake, are toxic in humans. Placental contamination by chemicals may act as a biologic marker for the exposure of the mother or for the fetus via transplacental transfer. Placentas were collected from term deliveries in two Slovak regions. The samples were then analyzed for 21 selected organochlorine compounds. Specimens of cord blood from 2,050 neonates were gathered for the determination of levels of total immunoglobulin E (IgE). The regions were chosen according to their environmental characteristics: a city polluted with organic chemical industry versus a rural region devoid of industrial sources of pollution. In addition, data regarding the incidence rate of atopic eczema cases in the regions were considered. Comparisons between regions revealed that both the placental contamination with 16 of 21 organochlorine compounds and the cord serum IgE levels were significantly higher in the industrial region. The findings pointed to an association between organochlorine compounds and the higher levels of total IgE in newborns, signaling a higher allergic sensitization in the industrial region. This association was supported by the higher incidence rate of atopic eczema cases in the population registered in the industrial region.
PMID: 10544157

30. Expression of CYP1B1 in human adult and fetal tissues and differential inducibility of CYP1B1 and CYP1A1 by Ah receptor ligands in human placenta and cultured cells

Hakkola J et al.
Carcinogenesis. 1997 Feb;18(2):391-7.
http://carcin.oxfordjournals.org/cgi/reprint/18/2/391

Expression of the Ah receptor-regulated cytochrome P4501B1 (CYP1B1) gene was studied in human adult and fetal tissues and cells in culture by reverse transcriptase-coupled polymerase chain reaction (RT-PCR). In adults, CYP1B1 mRNA was detected in liver, lymphocytes, cells of bronchoalveolar lavage samples and uterine endometrium, but not in lung. The level of expression was very low in adult liver and only three out of six fetal livers expressed CYP1B1. Extrahepatic fetal tissues, especially brains and kidneys, expressed high levels of CYP1B1. CYP1B1 mRNA was constitutively detected at a low level in first trimester and full-term placental samples. A competitive RT-PCR assay was developed to assess the regulation of CYP1B1. CYP1B1 mRNA was not induced in placenta by maternal cigarette smoking. Inducibility of CYP1B1 in cells in culture by the Ah receptor ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin was studied in primary fibroblasts and chorion carcinoma cell line JEG-3 having different CYP1A1 induction properties. Inducibility of CYP1B1 was found to be regulated independently from CYP1A1. In JEG-3 cells CYP1A1 mRNA was induced up to 9000-fold, while the expression of CYP1B1 was not affected. Expression of Ah receptor and Ah receptor nuclear translocator (regulators of the CYP1 family) was determined in human placenta and in the JEG-3 cell line. Expression of these transcription factors was found neither to be co-regulated nor affected by Ah receptor ligands. This study provides evidence that in addition to the Ah receptor complex, other cell-specific factors modulate the response of CYP1B1 and CYP1A1 to Ah receptor ligands.
PMID: 9054634

31. Placental markers of human exposure to polychlorinated biphenyls and polychlorinated dibenzofurans

Lucier GW et al.
Environ Health Perspect. 1987 Dec;76:79-87.
http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1474460&blobtype=pdf

Our studies have evaluated biochemical changes in placentae from humans exposed to rice oil contaminated with polychlorinated biphenyls (PCBs) and polychlorinated dibenzofurans (PCDFs) in Taiwan. Placentae were obtained from nonsmoking women 4 to 5 years after the exposure had occurred. The exposed individuals ingested approximately 1 to 3 g PCBs and 5 mg PCDFs, and many exhibited symptoms characteristic of PCB poisoning. This disease was termed "Yu-Cheng" in Chinese. Based on data from experimental animal models, we examined a number of parameters in placentae from control and exposed women, including arylhydrocarbon hydroxylase (AHH) activity, cytochrome P-450 isozymes, epidermal growth factor (EGF) receptor binding properties and actions, and Ah receptor. We also quantified concentrations of various PCB and PCDF congeners known to be present in the contaminated rice oil. Our results revealed a dramatic elevation in placental AHH activity in samples from PCB/PCDF-exposed women. This increase in enzyme activity was associated with a parallel increase in placental microsomal protein immunochemically related to cytochrome P-450 form 6 [derived from 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced rabbit lung]. No other cytochrome P-450 isozyme was detected in placental preparations, and the form 6 homolog was found only in placentae from exposed women. EGF receptor-mediated autophosphorylation capacity was significantly diminished in PCB/PCDF placentae, but this effect was not associated with changes in plasma membrane EGF receptor binding properties (Kd and Bmax). The EGF receptor autophosphorylation effect correlated well with the decrease in birthweight observed in offspring of exposed women, suggesting that this biochemical event might provide a good marker of effect for the toxic halogenated aromatics.
PMID: 2834196

32. Global Community Monitor & Bucket Brigade
http://www.gcmonitor.org