Nadia Abdelouahab

Perinatal Exposure to Low-Dose BDE-47, an Emergent Environmental Contaminant, Causes Hyperactivity in Rat Offspring

Background: Polybrominated diphenyl ethers (PBDE) are a group of environmental contaminants increasing in North America. Few data are available on neurobehavioral effects at low-dose exposure. Objectives: Our goal in the present study was to evaluate whether low-dose BDE-47, which is the most abundant PBDE in human samples, affects the neurobehavioral development of rats. Methods: Dams were exposed to vehicle or low-dose BDE-47 (0.002, 0.02 and 0.2 mg/kg body weight) each 5 days from gestational day 15 to postnatal day (PND) 20 by intravenous injections. Spontaneous locomotor activity of pups was assessed using the open field test on PND 15, 20 and 25. Sensorimotor coordination was assessed using a RotaRod on PND 30. Results: Exposure to BDE-47 increased locomotor activity of pups. Developmental landmarks and sensorimotor coordination were not influenced by exposure to BDE-47. BDE-47 content in adipose tissue of exposed rats was similar to that known for human populations. Conclusion: These results indicate neurodevelopmental disruption induced in rats by BDE-47 at levels found in the human population.

Maternal and Cord-Blood Thyroid Hormone Levels and Exposure to Polybrominated Diphenyl Ethers and Polychlorinated Biphenyls During Early Pregnancy

Thyroid hormones play a critical role in the growth of many organs, especially the brain. Polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) interact with the thyroid pathway and may disturb neurodevelopment. This prospective study was designed to examine associations between maternal blood PBDEs and PCBs in early pregnancy and levels of thyroid hormones in maternal and umbilical-cord blood. Levels of low-brominated PBDEs, 3 PCB congeners, total and free thyroid hormones (triiodothyronine (T3) and thyroxine (T4)), thyroid-stimulating hormone, thyroid peroxidase antibodies, iodine, selenium, and mercury were measured in 380 pregnant women in the first trimester who were recruited at the University Hospital Center of Sherbrooke (Quebec, Canada) between September 2007 and December 2008. Thyroid hormone levels were also assessed at delivery and in cord blood (n = 260). Data were analyzed on both a volume basis and a lipid basis. At less than 20 weeks of pregnancy, no relationship was statistically significant in volume-based analysis. In lipid-based models, an inverse association between maternal PBDEs and total T3 and total T4 and a direct association with free T3 and free T4 were observed. At delivery, in both analyses, we observed negative associations between maternal total T4, free T3, cord-blood free T4, and PBDEs and between maternal free T3 and PCBs. Our results suggest that exposure to PBDEs and PCBs in pregnancy may interfere with thyroid hormone levels.

Measurements of Selected Brominated Flame Retardants in Nursing Women: Implications for Human Exposure

We have examined several emerging brominated flame retardants (BFRs) including 2-ethyl-1-hexyl-2,3,4,5-tetrabromobenzoate (TBB), bis(2-ethylhexyl) tetrabromophthalate (TBPH), 1,2-bis(2,4,6-tribromophenoxy) ethane (BTBPE), 4,5,6,7-tetrabromo-1,1,3-trimethyl-3-(2,3,4,5-tetrabromophenyl)-indane (OBIND), and decabromodiphenyl ethane (DBDPE) in paired human maternal serum (n = 102) and breast milk (n = 105) collected in 2008–2009 in the Sherbrooke region in Canada. Three legacy BFRs were also included in the study for comparison: decabromobiphenyl (BB-209), 2,2′,4,4′,5,5′-hexabromobiphenyl (BB-153), and 2,2′,4,4′,5,5′-hexabromodiphenyl ethers (BDE-153). TBB, BB-153, and BDE-153 had detection frequencies greater than 55% in both serum and milk samples. Their lipid weight (lw) adjusted median concentrations (ng g–1 lw) in serum and milk were 1.6 and 0.41 for TBB, 0.48 and 0.31 for BB-153, and 1.5 and 4.4 for BDE-153, respectively. The detection frequencies for the other BFRs measured in serum and milk were 16.7% and 32.4% for TBPH, 3.9% and 0.0% for BTBPE, 2.0% and 0.0% for BB-209, 9.8% and 1.0% for OBIND, and 5.9% and 8.6% for DBDPE. The ratio of TBB over the sum of TBB and TBPH (fTBB) in serum (0.23) was lower than that in milk (0.46), indicating TBB has a larger tendency than TBPH to be redistributed from blood to milk. Overall, these data confirm the presence of non-PBDE BFRs in humans, and the need to better understand their sources, routes of exposure, and potential human health effects.

Thyroid Disruption by Low-Dose BDE-47 in Prenatally Exposed Lambs

The purpose of this study was to evaluate whether polybrominated diphenyl ethers (PBDE) at levels reported for human populations affect the thyroid state in pregnant sheep and lambs. Pregnant sheep were exposed to vehicle or BDE-47 (0.2, 2 and 20 μg/kg b.w.) from the 5th to 15th week of gestation by intravenous injections weekly. Thyroid hormone levels and BDE-47 content in the blood of sheep and lambs and adipose tissue were analyzed. We observed a significant decrease in total T4 and T3 in exposed lambs without any effect in pregnant sheep. Our finding indicates that prenatal low-dose PBDE exposure results in PBDE storage in fat of offspring and can affect thyroid metabolism in the developing fetus.

Ecosystem matters: Fish consumption, mercury intake and exposure among fluvial lake fish-eaters

Many studies use the number of fish meals as an estimate of Hg intake, although fish Hg concentrations, even within the same species, can greatly vary. Furthermore, most freshwater advisories only refer to local catch, while market fish advisories only focus on market fish, although both can contribute to Hg body burden. The present study, carried out in lakeside communities from 2 ecosystems in Quebec, Canada, sought to (i) estimate Hg intake from local freshwater sources, hunted waterfowl and market fish and seafood, and (ii) examine the relations between fish consumption, estimated Hg intake and biomarkers of exposure. A total of 238 adults (18-74 years), who had consumed local catch within the past three months, responded to an extensive interview-administered fish and waterfowl frequency questionnaire. Anthropometric measures were taken and a self-administered questionnaire was used to obtain socio-demographic information. Hg intake was estimated as microg Hg/kg body weight/day. Blood and hair samples were analyzed for Hg content. Results showed that persons from one ecosystem ate significantly more fish compared to those from the other (median: 52.1 g/day vs 38.9 g/day), but presented significantly lower concentrations of hair Hg (median: 448.0 ng/g vs 730.5 ng/g), blood organic Hg (median: 1.1 microg/L vs 3.4 microg/L) and inorganic Hg (median: 0.4 microg/L vs 0.8 microg/L). Median daily total Hg intake was 0.080 microg/kg bw/day for the former community and 0.141 microg/kg bw/day for the latter. Overall, 59.5% from the first ecosystem and 41.0% from the other, exceeded the US EPA RfD (0.1 microg/kg bw/day), while 13.2% and 6.0%, respectively, exceeded the Canadian tolerable daily intake (0.47 microg/kg bw/day) for adults. For the two groups, freshwater fish consumption frequency, but not total fish, was positively associated with bioindicators of Hg while estimated Hg intake from freshwater catch as well as from total fish consumption were positively related to Hg biomarkers. There was a positive relation between consumption and estimated Hg intake from freshwater fish and blood inorganic Hg. These findings indicate that the number of fish can be a poor surrogate for Hg exposure. The differences observed here for Hg intake and exposure reflect ecosystem disparities in fish diversity and Hg bioaccumulation. Studies and advisories need to consider Hg fish concentrations and fish-eating patterns in different ecosystems, as well as the contribution of market fish. The relation between fish consumption and inorganic Hg exposure, reported as well in other studies, needs to be further investigated.

Endocrine disruption in human placenta: expression of the dioxin-inducible enzyme, CYP1A1, is correlated with that of thyroid hormone-regulated genes.

CONTEXT Thyroid hormone (TH) is essential for normal development; therefore, disruption of TH action by a number of industrial chemicals is critical to identify. Several chemicals including polychlorinated biphenyls are metabolized by the dioxin-inducible enzyme CYP1A1; some of their metabolites can interact with the TH receptor. In animals, this mechanism is reflected by a strong correlation between the expression of CYP1A1 mRNA and TH-regulated mRNAs. If this mechanism occurs in humans, we expect that CYP1A1 expression will be positively correlated with the expression of genes regulated by TH. OBJECTIVE The objective of the study was to test the hypothesis that CYP1A1 mRNA expression is correlated with TH-regulated mRNAs in human placenta. METHODS One hundred sixty-four placental samples from pregnancies with no thyroid disease were obtained from the GESTE study (Sherbrooke, Québec, Canada). Maternal and cord blood TH levels were measured at birth. The mRNA levels of CYP1A1 and placental TH receptor targets [placental lactogen (PL) and GH-V] were quantitated by quantitative PCR. RESULTS CYP1A1 mRNA abundance varied 5-fold across 132 placental samples that had detectable CYP1A1 mRNA. CYP1A1 mRNA was positively correlated with PL (r = 0.64; P < .0001) and GH-V (P < .0001, r = 0.62) mRNA. PL and GH-V mRNA were correlated with each other (r = 0.95; P < .0001), suggesting a common activator. The mRNAs not regulated by TH were not correlated with CYP1A1 expression. CONCLUSIONS CYP1A1 mRNA expression is strongly associated with the expression of TH-regulated target gene mRNAs in human placenta, consistent with the endocrine-disrupting action of metabolites produced by CYP1A1.

Maternal levels of endocrine disruptors, polybrominated diphenyl ethers, in early pregnancy are not associated with lower birth weight in the Canadian birth cohort GESTE

BackgroundPolybrominated diphenyl ethers are known endocrine disrupting environmental contaminants used as flame retardants. Their levels have increased in humans over the last ten years, raising concerns about their consequences on human health. Some animal studies suggest that PBDEs can affect fetal growth; however, the results of human studies are contradictory. This study evaluates the association between the most common PBDEs in maternal blood measured in early pregnancy and birth weight.MethodsBDE-47, BDE-99, BDE-100 and BDE-153 levels were measured in 349 women during their first prenatal care visit at the University Hospital Center of Sherbrooke (Quebec, Canada). Birth weight and relevant medical information were collected from medical records. In contrast with previous studies, we examined the full range of clinical risk factors known to affect fetal growth as potential confounders, as well as other environmental pollutants that are likely to interact with fetal growth (polychlorinated biphenyls (PCBs), mercury, lead, cadmium and manganese).ResultsThere was no statistically significant relationship between PBDE levels in early pregnancy and birth weight in both unadjusted and multivariate regression models.ConclusionsOur results suggest that PBDEs in early pregnancy have little or no direct impact on birth weight, at least at the levels of exposure in our population.

Closure of the uterine incision with one or two layers after caesarean section: a randomized controlled study in sheep.

Abstract Objective: To compare the quality of the uterine scar with one or two layer closure after caesarean section by studying biomechanical and pathological properties of the scar. Methods: A randomized controlled trial performed on eight term pregnant ewes assigned into two groups during caesarean according to type of uterine closure: single-layer or double-layer. Hysterectomy was performed 8 months after caesarean delivery. Tensile strength of all scars and of unscarred myometrium was measured. Pathological properties of the scars were analyzed histologically. Results: The force required to reach the yield point was similar between scarred and unscarred myometrium (p = 0.96), and between the scars in single-layer and double-layer closure groups (p = 0.65). There was a significant increase in fibrosis width on the superficial part of the uterus in the double-layer closure group compared to the single-layer group (p = 0.02). Conclusions: Double-layer uterine closure modified wound healing without significant change in biomechanical properties.