Maternal Chemical Exposure Research Articles

Prenatal double-hit with aluminium and cadmium mediate testicular atrophy and hypothalamic hypoplasia: the role of oxido-nitrergic stress and endocrine perturbations.

There is limited experimental evidence on the biochemical consequences of aluminium (Al) and cadmium (Cd) co-exposures during pregnancy and postnatal life.This study investigated the impacts of perinatal Al chloride (AlCl3) and Cd chloride (CdCl2) co-exposures on neuroendocrine functions in mice offspring during postnatal life. The study comprised of four pregnant experimental groups. Group 1 received AlCl3 (10mg/kg), group 2 were administered CdCl2 (1.5mg/kg), while group 3 received both AlCl3 (10mg/kg) and CdCl2 (1.5mg/kg) (AlCl3+CdCl2), and group 4 received saline (10mL/kg) only and served as control group. All experimental animals were chemically exposed once daily from gestation days 7-20. Upon delivery, male pups were regrouped based on maternal chemical exposure on postnatal day 21 (PND 21) and allowed to grow to adulthood until PND 78, after which they were sacrificed for assessment of neuroendocrine markers and histological investigations. There was no statistical significance (p > 0.05) on follicle stimulating hormone, testosterone, estrogen and progesterone, thyroid stimulating hormone, thyroxine (T4) in all treatment groups relative to controls|. However, AlCl3 and AlCl3-CdCl2 significantly (p < 0.05) reduced triiodothyronine (T3) levels, with a profound increase in T3:T4 ratio by AlCl3, and AlCl3+CdCl2 compared to control. Furthermore, pups from pregnant mice treated with CdCl2 and AlCl3+CdCl2 demonstrated increased testicular malondialdehyde concentration with increased catalase activity relative to controls, suggesting oxidative imbalance. In addition, AlCl3, CdCl2, and AlCl3+CdCl2 exposures induced testicular and hypothalamic architectural disruption compared to controls, with marked architectural derangement in the AlCl3+CdCl2 group. Our findings suggest that prenatal co-exposures to Alcl3 and CdCl2 induce testicular and hypothalamic alterations in offspring via a testicular oxidative stress and thyrotoxicosis-dependent mechanisms.

Associations between the chemical exposome and pregnancy induced hypertension

Exposure to environmental chemicals has been linked to an increased risk of pregnancy-induced hypertension (PIH). This prospective cohort study examined the associations between PIH and maternal chemical exposure to four classes of chemicals (i.e., phthalates, bisphenols, perfluoroalkyl acids, non-essential metals and trace minerals). Participants included 420 pregnant women from the Alberta Pregnancy Outcomes and Nutrition (APrON) cohort who had data available on diagnosed PIH and environmental chemical exposure. Twelve phthalate metabolites, two bisphenols, eight perfluoroalkyl acids and eleven non-essential metals or trace minerals were quantified in maternal urine or blood samples collected in the second trimester of pregnancy. Associations between the urinary and blood concentrations of these chemicals and PIH were assessed using multiple logistic and LASSO regression analyses in single- and multi-chemical exposure models, respectively. Thirty-five (8.3%) participants were diagnosed with PIH. In single chemical exposure models, two phthalate metabolites, mono-methyl phthalate (MMP) and monoethyl phthalate (MEP), three perfluoroalkyl acids, perfluoroheptanoic acid (PFHpA), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA), and one metal, manganese, were associated with increased odds of PIH. The metabolites of di (2-ethylhexyl) phthalate (DEHP) and the molar sum of these metabolites, as well as antimony, displayed trend associations (p < 0.10). In multi-chemical exposure models using LASSO penalized regressions and double-LASSO regressions, MEP (AOR: 1.43, 95% CI: 1.09–1.88, p = 0.009) and PFNA (AOR: 2.03, 95% CI: 1.01–4.07, p = 0.04) were selected as the chemicals most highly associated with PIH. These findings suggest that maternal levels of phthalates and perfluoroalkyl acids may be associated with the diagnosis on PIH. Future research should consider both individual and multi-chemical exposures when examining predictors of PIH and other maternal cardiometabolic health disorders, such as preeclampsia, eclampsia, HELLP syndrome, and gestational diabetes.

Association between Maternal Exposure to Chemicals during Pregnancy and the Risk of Foetal Death: The Japan Environment and Children's Study.

Scarce knowledge is available on the relationship between maternal chemical exposure during pregnancy and foetal deaths. We studied the association of spontaneous abortions and stillbirths with occupational or daily maternal exposure to chemicals commonly used by pregnant women. Data from the Japan Environment and Children’s Study (JECS), a nationwide prospective birth cohort study, were used. The participants of the study were asked about the frequency of their use of gasoline, pesticides, hair dye, and chlorine bleach during the first and the second to third trimesters of pregnancy. We investigated the relationship between the frequency of the use of chemicals and foetal death. Of the 104,065 foetuses, 923 (0.91%) were spontaneous abortions and 379 (0.37%) were stillbirths. Any type of exposure during the first trimester was not significantly associated with spontaneous abortions. Nevertheless, a more than weekly occupational use of hair dye from the first to the second/third trimester was significantly associated with stillbirth. The results of this study suggest that the frequent use of hair dye during pregnancy can have severe adverse effects on the foetus. These findings can help pregnant women, especially hairdressers, refrain from the continuous use of hair dyes.

Early-Life Origins of Metabolic Syndrome: Mechanisms and Preventive Aspects.

One of the leading global public-health burdens is metabolic syndrome (MetS), despite the many advances in pharmacotherapies. MetS, now known as “developmental origins of health and disease” (DOHaD), can have its origins in early life. Offspring MetS can be programmed by various adverse early-life conditions, such as nutrition imbalance, maternal conditions or diseases, maternal chemical exposure, and medication use. Conversely, early interventions have shown potential to revoke programming processes to prevent MetS of developmental origins, namely reprogramming. In this review, we summarize what is currently known about adverse environmental insults implicated in MetS of developmental origins, including the fundamental underlying mechanisms. We also describe animal models that have been developed to study the developmental programming of MetS. This review extends previous research reviews by addressing implementation of reprogramming strategies to prevent the programming of MetS. These mechanism-targeted strategies include antioxidants, melatonin, resveratrol, probiotics/prebiotics, and amino acids. Much work remains to be accomplished to determine the insults that could induce MetS, to identify the mechanisms behind MetS programming, and to develop potential reprogramming strategies for clinical translation.

Prenatal Environment and Perinatal Factors Associated with Autism Spectrum Disorder

Background: Both genetic and epidemiological studies have indicated that environmental factors play an essential role in the development of autism spectrum disorder (ASD). We conducted this study to identify maternal exposure to environmental factors, in particular during the fetal development or perinatal period, associated with ASD. Methods: Two independent samples of children with ASD and typical developed (TD) were from distinct regions in China. Multiple logistic regression analysis was performed to identify factors associated with ASD in each sample and then in the combined sample. Results: Five factors were consistently associated with ASD in both samples. In the combined sample, maternal chemical exposure (odds ratio [OR] =4.50; 95% CI: 2.38-8.52), use of medication (OR = 3.19; 95% CI: 2.19-4.65), maternal infection (OR = 2.68; 95% CI: 1.99-3.61), threatened abortion (OR = 2.37; 95% CI: 1.61-3.50), and induced abortion before having the child (OR = 2.07; 95% CI: 1.65-2.60) showed strong associations with ASD; moreover, five factors explained 10-15% of the variation in the risk of ASD. A significant interaction between maternal infection and the use of medication during pregnancy was consistently detected in both independent and combined samples together. Conclusion: Two novel risk factors of maternal chemical exposure and induced abortion may have important implications for understanding the etiology of ASD, particularly in China. Prospective studies are needed to validate these findings, and necessary interventions are recommended to reduce the risk of ASD. KEYWORDS Autism spectrum disorder, chemical exposure, induced abortion, maternal infection

Telomere length and fetal programming: A review of recent scientific advances.

We sought to synthesize a comprehensive literature review comprising recent research linking fetal programming to fetal telomere length. We also explored the potential effects fetal telomere length shortening has on fetal phenotypes. Utilizing the PubMed database as our primary search engine, we retrieved and reviewed 165 articles of published research. The inclusion criteria limited the articles to those that appeared within the last ten years, were pertinent to humans, and without restriction to language of publication. Our results showed that socio-demographic factors like age, sex, genetic inheritance, and acquired disease impact telomere length. Further, we found several maternal characteristics to be associated with fetal telomere length shortening, and these include maternal chemical exposure (eg, tobacco smoke), maternal stress during pregnancy, maternal nutritional and sleeping disorders during pregnancy as well as maternal disease status. Due to paucity of data, our review could not synthesize evidence directly linking fetal phenotypes to telomere length shortening. Although the research summarized in this review shows some association between determinants of intrauterine programming and fetal telomere length, there is still significant work that needs to be done to delineate the direct relationship of telomere attrition with specific fetal phenotypes.

Association of exposure to environmental chemicals with risk of childhood acute lymphocytic leukemia

Objective: This study aimed to investigate the association between exposure to environmental chemicals and the risk of childhood acute lymphocytic leukemia(cALL). Methods: A case-controlled study was conducted in Shenzhen Children's Hospital, China from January 2015 to January 2016. The cases were selected from the section of Hematology and Oncology, and the controls were selected from Orthopedics by 1∶2 matching of cases according to sex and age. A questionnaire including population data and chemical exposure characteristics was conducted on the children's parents, and urine and EDTA-blood were collected from the children. Then, we quantitatively measured the internal dose of formaldehyde(i.e., formaldehyde-human serum albumin)by enzyme-linked immunosorbent assay and the doses of metabolites benzene, toluene, and xylene(i.e., trans-muconic acid, hippuric acid, and methylhippuric acid)by high-performance liquid chromatography. Logistic regression models were used to analyze the relationships between exposure factors measured from children and their parents and cALL. Results: In the study, 71 cases(average age: 6.08±3.61 years), and 142 controls(average age: 5.91±3.57 years)were assessed; there were no differences in general demographics between two groups. The self-reported results showed that living in a home that had been painted in the past 10 years(OR=4.39, 95% CI: 1.87-10.31), maternal chemical exposure during pregnancy(OR=11.78, 95% CI: 1.65-83.88), paternal diesel or gasoline exposure(OR=8.15, 95% CI: 2.68-24.83), paternal dye exposure(OR=7.77, 95% CI: 1.52-39.67)and trash burning near the child's residence(OR=6.08, 95% CI: 1.17-31.66)were associated with increased risk of cALL. The positive detection rates of only benzene metabolites were significantly higher in cases(40/44)than controls(81/111)(χ2=5.92, P=0.021). The median formaldehyde and benzene concentrations in cases(32.120 pg/ml, 2.505 μg/gCr)were significantly higher than those in controls(18.705 pg/ml, 0.672 μg/gCr; Z values:-1.98 and-3.95, P values: 0.047 and<0.001, respectively). Multiple logistic regression analysis showed that benzene exposure(OR=1.09, 95% CI: 1.00-1.19), home painting in the past 10 years(OR=3.56, 95% CI: 1.20-10.53)and paternal diesel or gasoline exposure(OR= 3.75, 95% CI: 1.06-13.22)were associated with increased risk of cALL. Conclusion: A variety of environmental chemistry factors, such as benzene exposure, increase the risk of cALL, and further studies are warranted to explore their specific roles.

Altered miRNA expression in the cervix during pregnancy associated with lead and mercury exposure.

Toxic metals including lead and mercury are associated with adverse pregnancy outcomes. This study aimed to assess the association between miRNA expression in the cervix during pregnancy with lead and mercury levels. We obtained cervical swabs from pregnant women (n = 60) and quantified cervical miRNA expression. Women's blood lead, bone lead and toenail mercury levels were analyzed. We performed linear regression to examine the association between metal levels and expression of 74 miRNAs adjusting for covariates. Seventeen miRNAs were negatively associated with toenail mercury levels, and tibial bone lead levels were associated with decreased expression of miR-575 and miR-4286. The findings highlight miRNAs in the human cervix as novel responders to maternal chemical exposure during pregnancy.

Mirna Expression in the Cervix Is Associated with Lead and Mercury Exposure during Pregnancy

Mirna Expression in the Cervix Is Associated with Lead and Mercury Exposure during PregnancyAbstract Number:2550 Alison Sanders*, Heather Burris, Allan Just, Katherine Svensson, Chitra Amarasiriwardena, Valeria Motta, Adriana Mercado-Garcia, Joel Schwartz, Martha Tellez-Rojo, Robert Wright, and Andrea Baccarelli Alison Sanders* Icahn School of Medicine at Mount Sinai, United States, E-mail Address: [email protected] Search for more papers by this author , Heather Burris Beth Isreal Deaconess Medical Center, Harvard Medical School, United States, E-mail Address: [email protected] Search for more papers by this author , Allan Just Harvard School of Public Health, United States, E-mail Address: [email protected] Search for more papers by this author , Katherine Svensson Icahn School of Medicine at Mount Sinai, United States, E-mail Address: [email protected] Search for more papers by this author , Chitra Amarasiriwardena Icahn School of Medicine at Mount Sinai, United States, E-mail Address: [email protected] Search for more papers by this author , Valeria Motta Harvard School of Public Health, United States, E-mail Address: [email protected] Search for more papers by this author , Adriana Mercado-Garcia National Institute of Public Health , Mexico, E-mail Address: [email protected] Search for more papers by this author , Joel Schwartz Harvard School of Public Health, United States, E-mail Address: [email protected] Search for more papers by this author , Martha Tellez-Rojo National Institute of Public Health , Mexico, E-mail Address: [email protected] Search for more papers by this author , Robert Wright Icahn School of Medicine at Mount Sinai, United States, E-mail Address: [email protected] Search for more papers by this author , and Andrea Baccarelli Harvard School of Public Health, United States, E-mail Address: [email protected] Search for more papers by this author AbstractToxic metals including lead (Pb) and mercury (Hg) are associated with adverse pregnancy outcomes. miRNAs are small non-coding RNAs that post-transcriptionally control gene expression. miRNAs are particularly susceptible to environmental exposures, and no previous studies have examined environmentally-associated alterations in cervix miRNA expression during pregnancy. This study aimed to analyze the association between miRNA expression in the cervix with Pb and Hg levels biomonitored during pregnancy. We obtained cervical swabs from 80 women between 18 to 20 weeks gestation in a cohort from Mexico City, Mexico. Cervical RNA was extracted and miRNA expression was quantified in a subset of 60 samples using the nCounter Analysis System from Nanostring. Women’s blood Pb was analyzed via ICP-MS and toenail Hg levels were analyzed with a direct Hg analyzer. We performed linear regression to examine the associations between expression of thirty-five miRNAs and metal exposures adjusting for women’s age, education, and environmental tobacco smoke. Expression of miR-188 was positively associated with maternal blood Pb levels (ß=0.3, p=0.04). Expression of let-7b (ß=-1.9, p=0.02), miR-205 (ß=-2.9, p=0.02), and miR-203 (ß=-2.3, p=0.03) were negatively associated with toenail Hg levels, whereas expression of miR-1283 (ß=1.4, p=0.01) and miR-888 (ß=1.0, p=0.03) were positively associated. Pathway analysis of the five Hg-associated miRNAs revealed enrichment for genes involved in cell cycle, cancer, and organismal injury and abnormalities (p=1x10-11). Notably, let-7, miR-205, and miR-203 are known to play a role in reproductive system diseases. We showed altered miRNA expression in the human cervix during pregnancy associated with biomonitored toxic metal levels. These findings highlight miRNAs as novel responders to maternal chemical exposure in specific tissues relevant to labor. The role of metals and cervical miRNA expression in pregnancy outcomes deserves further study.

Chemical Connexin Impairment in the Developing Gonad Associated with Offspring Infertility

A dramatical decline in human male reproductive function has been reported for the past 20 years. Many recent epidemiological, clinical and experimental findings suggest that the reproductive dysfunction could result from prenatal and neonatal chemical compound exposure. Even if numerous studies argue for a relationship between male infertility and environmental and/or occupational exposure, the molecular mechanisms by which these anti-reproductive compounds act are still unclear. Recent findings showed that a family of transmembranous proteins, connexins, regulates numerous physiological functions involved in the development such as cell proliferation, differentiation, migration and apoptosis. In the testis and the ovary, connexins are known to be essential for the establishment and the maintenance of spermatogenesis in males and oogenesis and folliculogenesis in females. Moreover, mutation of connexin genes leads to several developmental human diseases (myelin-related diseases, hearing loss, congenital cataract, skin disorders or more complex syndromes such as the oculodendrodigital dysplasia....) and altered connexin expression, trafficking and degradation are often associated with the tumoral process. We propose, in the present work, to give an overview of connexin expression and intercellular gap junction coupling during development: in preimplantation, implantation and postimplantation embryos. Moreover, we underline the impact of maternal chemical exposure on connexin expression during fetal gonad development and we link this effect to future offspring fertility.

PESTICIDES EXPOSURE AND THE RISK OF CHILDHOOD ACUTE LEUKEMIA

Background and Aims: Acute leukemia (AL) is one of the most common malignant tumors among children below the age of 15, and pesticide has been hypothesized as one of the risk factors for AL. In this study, the association between pesticide exposure and the risk of childhood AL is evaluated. Methods: A total of 248 patients with newly diagnosed AL were recruited from four pediatric hospitals in Shanghai between January 1, 2006 and December 31, 2010, and 111 controls were matched with the cases based on gender and age. Pesticide exposure was determined by questionnaire and by measuring of organophosphate pesticide (OP) metabolites including Diethyl phosphrate (DEP), Dimethyl phophrate (DMP), Dimethyl thiophosphrate (DMTP), Diethyl thiophosphrate (DETP) and Diethyl dithiophosphrate (DEDTP) in the subjects’ urine using gas chromatography with a flame photometric detector. Results: Total environmental chemical exposure of children [odds ratio (OR)= 9.320, 95% confidence interval (CI):2.842-30.568], maternal chemical exposure during pre-gestation and pregnancy (OR=3.333; 95%CI:1.524-7.289), household use of pesticides (OR=1.786; 95%CI:1.128-2.830), and household use of mosquito insecticides (OR=2.225; 95%CI:1.304-3.796) increased the risk of childhood AL. Median concentrations of organophosphate metabolites (DEP, DMP, DMTP, DETP and DEDTP) in the cases (5.7296, 9.6673, 14.0634, 4.3642, 3.8472µg/gCr respectively) were significantly higher than those in the controls (1.6901, 1.6828, 0.8451, 0.7221, 0.7221µg/gCr respectively) (P&lt;0.05). Conclusions: This study found that chemical exposure and household use of pesticides, especially mosquito insecticides, might be associated with childhood AL, based on higher urine OPs levels in children with AL compared with those in the controls. Our findings add some evidence to the hypothesis that pesticides might be a risk factor for childhood AL. This association of AL risk with pesticide exposure merits further studies to confirm the association.