Prenatal Polychlorinated Biphenyls Research Articles

Placental-brain axis in females detected within broadly impacted metabolic gene networks protects against prenatal PCB exposure.

Neurodevelopmental disorders have a strong male bias that is poorly understood. Placenta is a rich source of molecular information about environmental interactions with genetics (including biological sex), that affect the developing brain. We investigated placental-brain transcriptional responses in an established mouse model of prenatal exposure to a human-relevant mixture of polychlorinated biphenyls (PCBs). To understand sex, tissue, and dosage effects in embryonic (E18) brain and placenta by RNAseq, we used weighted gene correlation network analysis (WGCNA) to create correlated gene networks that could be compared across sex or tissue. WGCNA revealed that expression within most correlated gene networks was significantly and strongly associated with PCB exposures, but frequently in opposite directions between male-female and placenta-brain comparisons. In both WGCNA and differentially expressed gene analyses, male brain showed more PCB-induced transcriptional changes than male placenta, but the reverse pattern was seen in females. Furthermore, non-monotonic dose responses to PCBs were observed in most gene networks but were most prominent in male brain. The transcriptomic effects of low dose PCB exposure were significantly reversed by dietary folic acid supplementation across both sexes, but these effects were strongest in female placenta. PCB-dysregulated and folic acid-reversed gene networks were commonly enriched in functions in metabolic pathways involved in energy usage and translation, with female-specific protective effects enriched in PPAR, thermogenesis, glycerolipids, and O-glycan biosynthesis, as opposed to toxicant responses in male brain. The female protective effect in prenatal PCB exposures appears to be mediated by dose-dependent sex differences in transcriptional modulation of metabolism in placenta.

Prenatal and postnatal exposure to polychlorinated biphenyls alter follicle numbers, gene expression, and a proliferation marker in the rat ovary

Polychlorinated biphenyls (PCBs) were used in industrial applications until they were banned in the 1970s, but they still persist in the environment. Little is known about the long-term effects of exposure to PCB mixtures on the rat ovary during critical developmental periods. Thus, this study tested whether prenatal and postnatal exposures to PCBs affect follicle numbers and gene expression in the ovaries of F1 offspring. Sprague-Dawley rats were treated with vehicle or Aroclor 1221 (A1221) at 1 mg/kg/day during embryonic days 8–18 and/or postnatal days (PND) 1–21. Ovaries from F1 rats were collected for assessment of follicle numbers and differential expression of estrogen receptor 1 (Esr1), estrogen receptor 2 (Esr2), androgen receptor (Ar), progesterone receptor (Pgr), and Ki-67 (Ki67) at PNDs 8, 32, and 60. Sera were collected for measurement of estradiol concentrations. Prenatal exposure to A1221 significantly decreased the number of primordial follicles and the total number of follicles at PND 32 compared to control. Postnatal PCB exposure borderline increased Ki67 gene expression and significantly increased Ki67 protein levels (PND 60) compared to control. Combined prenatal and postnatal PCB exposure borderline decreased Ar expression (PND 8) compared to control. However, PCB exposure did not significantly affect the expression of Pgr, Esr1, and Esr2 or serum estradiol concentrations compared to control at any time point. In conclusion, these data suggest that PCB exposure affects follicle numbers and levels of the proliferation marker Ki67, but it does not affect expression of some sex steroid hormone receptors in the rat ovary.

Prenatal Environmental Exposure to Persistent Organic Pollutants and Reproductive Hormone Profile and Pubertal Development in Dutch Adolescents.

Persistent organic pollutants (POPs), such as polychlorinated biphenyls (PCBs), may interfere with hormonal processes. Knowledge about the effects of prenatal exposure to PCBs and their hydroxylated metabolites (OH-PCBs) on pubertal development is limited. Therefore, the aim of the current study was to determine whether prenatal environmental PCB and OH-PCB exposure are associated with reproductive hormone levels and pubertal characteristics in 13- to 15-year-old children. In this Dutch observational cohort study, 194 mother–infant pairs were included (1998–2002). Maternal pregnancy serum levels of PCBs, OH-PCBs, and other POPs were measured. At follow-up (2014–2016), we measured serum or plasma levels of reproductive hormones in their children. We assessed Tanner stages and testicular volume (by clinician or standardized self-assessment), and participants completed questionnaires on pubertal onset. In total, 101 adolescents (14.4 ± 0.8 years; 53.7% of invited) participated, and 55 were boys. In boys, higher prenatal PCB levels were associated with higher testosterone levels, higher pubic hair stage, larger testicular volume, and younger age at onset of growth spurt and voice break. In girls, higher prenatal PCB levels were associated with higher stages for breast development. In conclusion, higher prenatal PCB exposure could be associated with more advanced pubertal development in 13- to 15-year-old children.

In Utero Exposure to 3,3',4,4', 5-Pentachlorobiphenyl Dose-Dependently Induces N-butyl-4-(hydroxybutyl) Nitrosamine in Rats With Urinary Bladder Carcinoma.

Polychlorinated biphenyls (PCBs) are fat-soluble environmental pollutants that can accumulate in adipose tissue or be secreted in milk. N-butyl-4-(hydroxy butyl) (BBN), a rat bladder carcinogen, recruits the host metabolism to yield its ultimate carcinogenic form via CYP1s. Since estrogen receptors (ERs) mediate biological responses important for the growth of bladder carcinoma, we investigated PCNA, Cyclin D1, ERs, CYP1s, and AhR expression in BBN rat bladder carcinomas with prenatal PCB exposure. Female SD rats were treated with 7.5 μg, 250 ng, and 2.5 ng of 3,3',4,4',5-pentachlorobiphenyl (PCB126)/kg or vehicle on days 13 to 19 post-pregnancy. Six-week-old male offspring were treated with 0.05% BBN for 10 weeks before being anesthetized and the urinary bladder wall incised to expose the bladder carcinomas. N-butyl-4-(hydroxybutyl) bladder carcinoma incidence increased with prenatal PCB exposure dose-dependently. In bladder carcinoma, PCB126 exposure significantly increased PCNA, D1, ERα, CYPIA1, CYP1B1, and AhR expression dose-dependently, and increased ERα expression was particularly prominent. However, the expression of ERβ was low, independent of the volume of PCB126 given, indicating similarity to the Vehicle group. We conclude that prenatal PCB126 exposure in rats can induce PCB126 to dose-dependently metabolize BBN via CYP1A1, and contribute to bladder carcinogenesis with upregulation of ERα expression.

Effects of endocrine-disrupting chemicals on hypothalamic oxytocin and vasopressin systems.

Exposures to endocrine disrupting chemicals (EDCs) perturb hormonal systems. EDCs are particularly problematic when exposure happens in the fetus and infant due to the high sensitivity of developing organisms to hormone actions. Previous work has shown that prenatal polychlorinated biphenyl (PCB) exposure disrupts hypothalamic development, reproductive physiology, mate preference behavior, and social behaviors in a sexually dimorphic manner. Based on evidence that EDCs perturb social behaviors in rodents, we examined effects of PCBs on the neuropeptides oxytocin (OXT) and vasopressin (AVP) that are involved in regulating these behaviors. Rats were exposed prenatally (gestational days 16 and 18) to the weakly estrogenic PCB mixture Aroclor 1221 (0.5 or 1 mg/kg), to estradiol benzoate (EB, a positive control), or to the vehicle (3% dimethyl sulfoxide). In adult (~P90) brains, we counted immunolabeled oxytocin and vasopressin cell numbers in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) of the hypothalamus. EDCs did not change absolute numbers of oxytocin or vasopressin cells in either region, although there were some modest shifts in the rostral-caudal distribution. Second, expression of genes for these nonapeptides (Oxt, Avp), their receptors (Oxtr, Avpr1a), and the estrogen receptor beta (Esr2), was determined by qPCR. In the PVN, there were dose-dependent effects of PCBs in males (Oxt, Oxtr), and effects of EB in females (Avp, Esr2). In the SON, Oxt, and Esr2 were affected by treatments in males. These changes to protein and gene expression caused by prenatal treatments suggest that transcriptional and posttranscriptional mechanisms play roles in mediating how EDCs reprogram hypothalamic development.

Transgenerational effects of polychlorinated biphenyls: 2. Hypothalamic gene expression in rats†.

Polychlorinated biphenyls (PCBs) are endocrine-disrupting chemicals (EDCs) with well-established effects on reproduction and behavior in developmentally-exposed (F1) individuals. Because of evidence for transgenerational effects of EDCs on the neuroendocrine control of reproductive physiology, we tested the hypothesis that prenatal PCB exposure leads to unique hypothalamic gene-expression profiles in three generations. Pregnant Sprague-Dawley rats were treated on gestational days 16 and 18 with the PCB mixture Aroclor 1221 (A1221), vehicle (3% DMSO in sesame oil), or estradiol benzoate (EB, 50μg/kg), the latter a positive control for estrogenic effects of A1221. Maternal- and paternal-lineage F2 and F3 generations were bred using untreated partners. The anteroventral periventricular nucleus (AVPV) and arcuate nucleus (ARC), involved in the hypothalamic control of reproduction, were dissected from F1 to F3 females and males, RNA extracted, and gene expression measured in a qPCR array. We detected unique gene-expression profiles in each generation, which were sex- and lineage-specific. In the AVPV, treatment significantly changed 10, 25, and 11 transcripts in F1, F2, and F3 generations, whereas 10, 1, and 12 transcripts were changed in these generations in the ARC. In the F1 AVPV and ARC, most affected transcripts were decreased by A1221. In the F2 AVPV, most effects of A1221 were observed in females of the maternal lineage, whereas only Pomc expression changed in the F2 ARC (by EB). The F3 AVPV and ARC were mainly affected by EB. It is notable that results in one generation do not predict results in another, and that lineage was a major determinant in results. Thus, transient prenatal exposure of F1 rats to A1221 or EB can alter hypothalamic gene expression across three generations in a sex- and lineage-dependent manner, leading to the conclusion that the legacy of PCBs continues for generations.

Evidence for differential thyroid sensitivity from prenatal exposure to polychlorinated biphenyl chemicals in children with autism

Background/Aim: Prenatal exposure to polychlorinated biphenyls (PCBs), persistent organic pollutants, is linked to altered thyroid function and adverse neurodevelopmental outcomes, including autism spectrum disorder (ASD). We examined whether neonatal thyroid-stimulating hormone (TSH) mediates the relationship between prenatal PCB exposure and risk of ASD. Methods: We analyzed data from the Early Markers for Autism (EMA) Study, a case-control study of children born during 2000-2003 in Southern California. Children diagnosed with ASD (n=523), Intellectual disability (ID; n=147), and general population controls (n=405) were identified from birth and Department of Developmental Services records. Eleven PCB congeners were measured above the limit of detection in maternal serum collected during the second trimester and modeled as quartiles. Neonatal TSH levels were obtained from state newborn screening records and ln-transformed. We assessed relationships between PCBs and neonatal TSH in models stratified by neurodevelopmental outcome and TSH mediation of the significant relationships we previously observed in EMA between several PCBs and ASD. Results: In the full sample, correlations between PCB concentrations and neonatal TSH were weak and not significant (ranging from 0 to 0.06). However, among children with ASD, we observed significant increases in neonatal TSH associated with an interquartile increase in prenatal levels of four PCBs, including PCB153 (adj-β: 0.21, 95%CI: 0.02-0.39) and PCB138/158 (adj-β: 0.19, 95%CI: 0.01-0.37). We did not observe associations between neonatal TSH and PCBs among children with ID only or controls. Mediation analyses did not suggest that relationships between these PCBs and ASD were mediated by neonatal TSH. Conclusions: Prenatal exposure to PCBs, particularly congeners previously found to be associated with ASD in EMA, were positively associated with neonatal TSH, but only among children subsequently diagnosed with ASD. These findings, needing replication in larger cohorts, may indicate differential fetal sensitivity to thyroid-disrupting chemicals among individuals born, and later-diagnosed, with ASD.

Prenatal exposure to trichlorinated biphenyls (PCB 18 and 28) is associated with child hyperactivity 8 years later

Background: Polychlorinated biphenyl (PCB) exposure may be associated with neurodevelopmental problems, particularly hyperactivity and attention deficit/hyperactivity disorder (ADHD). In animal studies, exposure to PCBs increased hyperactivity, decreased dopamine in key brain regions, and PCB 28, 47, and 52 were found in those regions. Dopamine has also been implicated in the etiology of ADHD in humans. Most epidemiologic studies have relied on maternal blood rather than newborn blood to quantify prenatal PCB exposure, and neonatal levels might better reflect fetal exposure. Methods: Whole-blood concentrations of PCB congeners #8, 15, 18, 28, 52, 70, 95, 101, 138, and 153 were measured in the Upstate KIDS study, a population-based longitudinal study of children born in New York State between 2008-2010, using newborn dried blood spots (n=2610). PCBs were quantified (ng/mL) using gas chromatography-DFS high resolution mass spectrometry. Individual blood spots provided insufficient volume for assays, so pools of 5 were used, and individual values were derived from pools. Child hyperactivity symptoms (Mean=4.82, SD=5.13) were assessed by maternal report on the Vanderbilt ADHD Parent Rating Scale when children were 8 years of age. Models were adjusted for child age, sex, and plurality, and maternal age, education, race/ethnicity, insurance status, marital status, pre-pregnancy body mass index, gestational weight gain, parity, and pregnancy smoking. Results: Each 1 ng/mL increase in PCB 18 and PCB 28 was associated with 3.63 (95%CI=0.42-6.84) and 4.08 (95%CI=0.61-7.55) more points in hyperactive behavioral ratings, respectively. Except for PCB 15, other PCBs also had positive but imprecise relations with hyperactivity. Conclusions: Levels of PCBs in newborn blood spots were associated with less than 1 standard deviation higher hyperactivity 8 years later. Even low-level prenatal exposure may have long-term behavioral consequences.

Prenatal environmental exposures and associations with teen births.

Background:Children’s prenatal exposure to multiple environmental chemicals may contribute to subsequent deficits in impulse control, predisposing them to risk-taking.Objective:Our goal was to investigate associations between prenatal exposure mixtures and risk of teen birth, a manifestation of high-risk sexual activity, among 5,865 girls (1st generation) born in southeast Massachusetts from 1992-1998.Methods:Exposures included prenatal modeled polychlorinated biphenyls (PCBs), ρ,ρ′-dichlorodiphenyl dichloroethylene (DDE), hexachlorobenzene (HCB), lead (Pb), and mercury (Hg). We fit adjusted generalized additive models with multivariable smooths of exposure mixtures, 1st generation infant’s birth year, and maternal age at 1st generation birth. Predicted odds ratios (ORs) for teen birth were mapped as a function of joint exposures. We also conducted sensitivity analyses among 1st generation girls with measured exposure biomarkers (n=371).Results:The highest teen birth risk was associated with a mixture of high prenatal HCB, Hg, Pb, and PCB, but low DDE exposure, with similar associations in sensitivity analyses. The highest OR predicted for girls born in 1995 to mothers of median age (26 years) was at the 95th percentile of the HCB and PCB exposure distributions (OR=3.09; 95% confidence interval: 0.29, 32.4). Additionally, girls born earlier in the study period or to teen mothers were at increased risk of teen birth.Significance:Prenatal environmental chemical exposures and sociodemographic characteristics may interact to substantially increase risk of teen births.

Exposure to prenatal PCBs shifts the timing of neurogenesis in the hypothalamus of developing rats.

The developing brain is highly sensitive to the hormonal milieu, with gonadal steroid hormones involved in neurogenesis, neural survival, and brain organization. Limited available evidence suggests that endocrine-disrupting chemicals (EDCs) may perturb these developmental processes. In this study, we tested the hypothesis that prenatal exposure to a mixture of polychlorinated biphenyls (PCBs), Aroclor 1221, would disrupt the normal timing of neurogenesis in two hypothalamic regions: the ventromedial nucleus (VMN) and the preoptic area (POA). These regions were selected because of their important roles in the control of sociosexual behaviors that are perturbed in adulthood by prenatal EDC exposure. Pregnant Sprague-Dawley rats were exposed to PCBs from Embryonic Day 8 (E8) to E18, encompassing the period of neurogenesis of all hypothalamic neurons. To determine the birth dates of neurons, bromo-2-deoxy-5-uridine (BrdU) was administered to dams on E12, E14, or E16. On the day after birth, male and female pups were perfused, brains immunolabeled for BrdU, and numbers of cells counted. In the VMN, exposure to PCBs significantly advanced the timing of neurogenesis compared to vehicle-treated pups, without changing the total number of BrdU+ cells. In the POA, PCBs did not change the timing of neurogenesis nor the total number of cells born. This is the first study to show that PCBs can shift the timing of neurogenesis in the hypothalamus, specifically in the VMN but not the POA. This result has implications for functions controlled by the VMN, especially sociosexual behaviors, as well as for sexual selection more generally.

Prenatal exposure to Polychlorinated Biphenyls and body fatness in girls

Polychlorinated biphenyls (PCBs) are synthetic, organochlorine compounds previously used in industrial processes. Although banned in 1980’s across Europe, these chemicals persist in the environment and are associated with adverse health outcomes in children. We investigated the association between in utero concentrations of PCBs and girls' body fatness. Concentrations of various PCB congeners (PCB 118, PCB 138, PCB 153, PCB 170, and PCB 180) were measured in maternal serum samples collected in the early 1990’s. Body fatness was measured in the daughters at 9 y of age using body mass index (BMI) and dual-energy x-ray absorptiometry (DXA) for percent body fat. Using multivariable linear regression, we explored associations between prenatal PCB congener concentrations and body fatness outcomes.Among 339 mother-daughter dyads, the median and interquartile range (IQR) for PCB congeners ranged between 15.0 ng g−1 (11.0–20.8) for PCB 118 to 64.6 ng g−1 (48.6–86.3) for PCB 153. Among daughters, the median was 27.5% (21.7–34.6) for percent body fat, 39.6% (36.4–43.5) for percent trunk fat, 4.9 kg m−2 (3.5–7.0) for fat mass index and 18.1 kg m−2 (16.3–20.6) for body mass index. Multivariable-adjusted regression analyses showed little or no association between prenatal PCB concentrations with daughters’ body fatness measures. Prenatal concentrations of PCB congeners were not strongly associated with measures of body fatness in girls.

Prenatal exposure to PCBs and neurological and sexual/pubertal development from birth to adolescence

Several chemical compounds are resistant to degradation and end up in the food chain. One group of these chemicals is polychlorinated biphenyls (PCBs) which are used as flame retardants and plasticizers. Although PCBs were banned several decades ago, PCBs are still found in environmental media, including in the body of humans. PCBs are transferred from mother to fetus via the placenta during pregnancy. Considering that the prenatal period is a sensitive period during which essential developmental processes take place, exposure to environmental chemicals might have considerable and permanent consequences for outcomes in later life. The aim of this review is to provide an update on the latest insights on the effects of prenatal exposure to PCBs on neurological, sexual and pubertal development in children. We give an overview of recent literature, and discuss it in the light of the findings in a unique Dutch birth cohort, with data on both neurological and pubertal development into adolescence. The findings in the studies included in this review, together with the findings in the Dutch cohort, demonstrate that prenatal exposure to PCBs can interfere with normal child development, not only during the perinatal period, but up to and including adolescence. Higher prenatal exposure to PCBs was found to be both negatively and positively associated with neurodevelopmental outcomes. Regarding pubertal development, higher prenatal PCB exposure was found to be associated with more advanced pubertal development, also in the Dutch cohort, whereas other studies also found delayed pubertal development. These findings raise concern regarding the effects of man-made chemical compounds on child development. They further contribute to the awareness of how environmental chemical compounds can interfere with child development and negatively influence healthy ageing.

Human prenatal exposure to polychlorinated biphenyls (PCBs) and risk behaviors in adolescence

Polychlorinated biphenyls (PCBs) are chemicals used in a variety of products before they were widely banned due to toxic effects in humans and wildlife. Because of continued persistence and ubiquity of these contaminants, risk of exposure to people living in industrialized countries is still high. Experimental research show that developmental exposure to PCB may alter function of brain pleasure centers and potentially influence disinhibitory behaviors, including tobacco and alcohol use. Yet, the potential effects of developmental PCB exposure on adolescent substance use have not been studied in humans. We used the Child Health and Development Studies (CHDS), a prospective birth cohort study in the Oakland and East Bay areas of California, to investigate associations between prenatal exposure to PCB congeners (66, 74, 99, 118, 138, 153, 170, 180, 187, and 203) and later disinhibitory behaviors in adolescents, specifically alcohol consumption and smoking, in a randomly selected sample (n = 554). Total prenatal PCB exposure was not associated with disinhibitory behaviors, among adolescents. However, the adjusted odds ratio (aOR) for being a current smoker, was higher in subjects within the third quartile of maternal PCB 66 exposure compared to those below the median (aOR = 1.93; 95% CI 1.05, 3.55). The aOR for drinking >2 alcoholic beverages per week, were also higher for adolescents within the third (aOR = 1.46; 95% CI 0.86, 2.47) and fourth quartile of PCB 66 exposure (aOR = 1.39; 95% CI 0.83, 2.35), but the differences did not reach statistical significance. These results suggest that this specific PCB congener may play a role inducing neurodevelopmental alterations that could potentially increase the risk of becoming a long-term user of tobacco and possibly alcohol. There were no notable differences between magnitude or direction of effect between boys and girls. Future replicate analyses with larger longitudinal samples and animal experimental studies of potential underlying mechanisms are warranted.

Neuroimaging signatures of brain plasticity in adults with prenatal exposure to polychlorinated biphenyls: Altered functional connectivity on functional MRI

Prenatal exposure to polychlorinated biphenyls (PCBs), persistent organic pollutants in food chains and environment, exerts negative effects on children's cognitive function. To study the long-term effects, we examined cognitive functions in the male children of women with substantial PCB exposure in Taiwan during 1978–1979 and investigated neural basis of cognitive function changes through structural magnetic resonance imaging (MRI) and functional MRI (fMRI), which included resting-state and task-activated fMRI with two paradigms: a 2-back task and a picture rotation task. Ten men aged 30.0 ± 3.7 years with prenatal exposure to PCBs and 11 unexposed controls aged 28.1 ± 3.1 years participated. Both groups had similar cognitive phenotypes and behavioral results. Structural MRI analysis results showed that the PCB group had increased cortical thickness over the right inferior parietal lobule. In the resting-state study, the PCB group showed alterations in the default mode network. During the tasks, the PCB group showed decreased task-induced deactivation signals in cognition–associated brain areas during the 2-back task but enhanced deactivations during the picture rotation task. This study demonstrated altered structural MRI as well as resting and task-related fMRI in men with prenatal PCB exposure, suggesting altered brain plasticity and compensatory neuropsychological performance.

Social and neuromolecular phenotypes are programmed by prenatal exposures to endocrine-disrupting chemicals

Exposures to endocrine-disrupting chemicals (EDCs) affect the development of hormone-sensitive neural circuits, the proper organization of which are necessary for the manifestation of appropriate adult social and sexual behaviors. We examined whether prenatal exposure to polychlorinated biphenyls (PCBs), a family of ubiquitous industrial contaminants detectable in virtually all humans and wildlife, caused changes in sexually-dimorphic social interactions and communications, and profiled the underlying neuromolecular phenotype. Rats were treated with a PCB commercial mixture, Aroclor 1221 (A1221), estradiol benzoate (EB) as a positive control for estrogenic effects of A1221, or the vehicle (4% DMSO), on embryonic day (E) 16 and 18. In adult F1 offspring, we first conducted tests of ultrasonic vocalization (USV) calls in a sociosexual context as a measure of motivated communications. Numbers of certain USV call types were significantly increased by prenatal treatment with A1221 in males, and decreased by EB in females. In a test of sociosexual preference for a hormone-vs. a non-hormone-primed opposite sex conspecific, male (but not female) nose-touching with opposite-sex rats was significantly diminished by EDCs. Gene expression profiling was conducted in two brain regions that are part of the social decision-making network in the brain: the medial preoptic nucleus (MPN) and the ventromedial nucleus (VMN). In both regions, many more genes were affected by A1221 or EB in females than males. In female MPN, A1221 changed expression of steroid hormone receptor and neuropeptide genes (e.g., Ar, Esr1, Esr2, and Kiss1). In male MPN, only Per2 was affected by A1221. The VMN had a number of genes affected by EB compared to vehicle (females: Kiss1, Kiss1r, Pgr; males: Crh) but not A1221. These differences between EB and A1221 indicate that the mechanism of action of A1221 goes beyond estrogenic pathways. These data show sex-specific effects of prenatal PCBs on adult behaviors and the neuromolecular phenotype.

Prenatal Exposure to Polychlorinated Biphenyls and Mercury Are Associated with Insulin-Like Growth Factor 1 and Thyroid-Stimulating Hormone in Cord Plasma

Impact on maternal endocrine system during pregnancy may also affect growth and development of a fetus. Certain toxic elements and polychlorinated biphenyls (PCBs) are known to disturbe human endocrine system. In our previous study, we showed that birth weight were affected by prenatal PCBs and methylmercury exposure. In this study, we used the data from the Tohoku Study of Child Development in Japan. The objective of the study was to evaluate the effect of prenatal exposure to methylmercury, arsenic, cadmium, lead, and PCBs on insulin-like growth factor 1 (IGF-1) and thyroid related hormones (TSH, T3, freeT3, T4 and freeT4) in cord blood. Those factros are considered to be associated with fetal growth. Elements except for mercury were analyzed by an inductivity coupled plasma mass spectrometry. Mercury levels were measured using a cold vapor atomic absorption spectrometer. IGF-1 and insulin-like growth factor binding protein 1 (IGFBP1) were detemined by an enzyme-linked immunosorbent assay (ELISA). Thyroid related hormones were assessed by an electrochemiluminescence immunoassay. The data were examined by Pearson’s correlation and multiple regression analyses. The IGF-1 in cord plasma was negatively associated with PCB concentrations in cord blood, especially with tri-, tetra-, penta-, hexa- and hepta-chlorobiphenyls. Cord plasma free T4 was negatively associated with mercury concentrations in cord blood. This study indicated PCBs and mercury could affect birth weight through altering the IGF1 and T4 mechanism. Further studies are necessary to investigate the effect of decrease in IGF-1 and thyroid hormones on birth weight.

Prenatal exposure to polychlorinated biphenyls and asthma, eczema/hay fever, and frequent ear infections

ABSTRACTObjectives: The effects of prenatal exposure to Polychlorinated biphenyls (PCBs) on the development of asthma, frequent ear infections, and eczema/hay fever are not well understood. We aim to investigate associations between prenatal PCB exposure and these health outcomes in the offspring of women who worked at the LaSalle Electrical Utilities Company (EUC). Methods: A retrospective cohort with at least one live birth and known employment time at EUC was eligible for this analysis. Exposure was defined and categorized by the number of fiscal quarters worked during the PCB era (1952–1981). A total of 288 women with 800 live births were included. A Chi-Square test was used to compare maternal and child characteristics across exposure groups and repeated measures logistic regression, controlling for clustering among siblings, was used to assess the associations between prenatal PCB exposure and these outcomes. Results: After adjustment for confounding and independent maternal predictors, 1–4 quarters of prenatal exposure to PCBs increased the odds for asthma (OR 3.24[1.30–8.09]), eczema/hay fever (OR 3.29[1.54–7.04]), and frequent ear infections (OR 2.24[1.19–4.22]) when compared with persons unexposed/exposed only to naphthalenes. The significance of the associations varied by exposure period and level of exposure, with the strongest associations in those employed exclusively after 1952 when PCBs were introduced. Conclusions: These results support previous findings of associations of prenatal exposure to PCBs with asthma, eczema/hay fever, and frequent ear infections. Additional prospective studies are needed to confirm these findings. Also required are more precise PCB exposures to separate them from other exposures in occupational settings.

Erratum: "Prenatal PBDE and PCB Exposures and Reading, Cognition, and Externalizing Behavior in Children".

[This corrects the article DOI: 10.1289/EHP478.].

Effects of intrauterine exposures to polychlorinated biphenyls, methylmercury, and lead on birth weight in Japanese male and female newborns

BackgroundThe effects of prenatal exposures to polychlorinated biphenyls (PCBs), methylmercury, and lead on birth weight remain disputable. The aim of this study was to investigate whether these chemicals affect birth weight of Japanese newborns, with special emphasis on determining whether these effects differ between males and females.MethodsThe subjects from Tohoku Study of Child Development, which was designed to examine the developmental effects of prenatal exposures to such hazardous chemicals, were 489 mother-newborn pairs with complete data including smoking habit during pregnancy.ResultsThe mean birth weight of all newborns was 3083 (range, 2412–4240) g. The median values of biomarkers in cord blood were 46.0 (5th and 95th percentiles, 18.6–113.8) ng/g–lipid for total PCBs, 10.1 (4.3–22.4) ng/g for total mercury (THg), and 1.0 (0.6-1.7) μg/dL for lead. The birth weight was significantly heavier in the 252 male newborns than in the 237 female ones. A negative association between total PCBs and birth weight was observed in both male and female newborns, even after adjusting for possible confounders. However, a negative association of THg with birth weight was found only in the male newborns. There was no significant relationship between lead and birth weight in both groups.ConclusionBirth weight appears to be affected by prenatal PCB exposure in Japanese male and female newborns, and the effect of methylmercury exposure on male fetal growth may be stronger than that for females. This implication is that the effects on fetal growth should be assessed in males and females separately.

Polychlorinated biphenyls: New evidence from the last decade.

Millions of pounds of polychlorinated biphenyl (PCB) compounds have been produced in multiple countries for industrial applications over the last several decades. PCB exposure induces various adverse health effects in animals and humans. Environmental and occupational exposures to PCBs have been associated with liver, kidney, endocrine, and neurodevelopmental adverse effects. We have collected and reviewed animal and human data cited in the US National Library of Medicine from 2000 to 2010. In brief, our review shows new evidence, that is, in animal studies, exposure to one of the PCBs, A1221, induces a significant alteration of serum luteinizing hormone. The effects were more profound in the F2 generation, particularly with respect to fluctuations in hormones and reproductive tract tissues across the estrous cycle. Morphological analyses of brain tissue from rats exposed to A1254 confirmed the results of an earlier work which showed that the relative size of the intra- and infrapyramidal (II-P) mossy fibers was smaller than that in the controls and also reduction in growth was selective for the II-P mossy fibers. PCB exposure increased anogenital distance and prostate size but decreased epididymal weight, epididymal sperm count, and motile epididymal sperm count. No effects were observed on testicular weight or size. The epidemiological data showed an association between diabetes mellitus prevalence and elevated concentrations of PCB 153. Additionally, prenatal PCB exposure studies were associated with a smaller thymic index at birth and could adversely affect immune responses to childhood vaccinations and resistance to respiratory infections. PCB exposure was also reported to adversely affect enamel development in children in a dose-dependent manner. Because PCBs and their metabolites are potential health hazards, understanding the risk factors associated with individual PCBs, PCB mixtures, and PCB metabolites is important. PCB exposures of vulnerable populations (pregnant women, fetuses, infants, and children) are of particular concern because of heightened sensitivity during this period of brain development.