Heightened susceptibility: A review of how pregnancy and chemical exposures influence maternal health

Varshavsky, Julia; Smith, Anna R.; Wang, Aolin; Hom, Elizabeth; Izano, Monika A.; Huang, Hongtai; Padula, Amy; Woodruff, Tracey J.

doi:10.1016/j.reprotox.2019.04.004

Cited by 116 publications

(76 citation statements)

References 193 publications

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“…These added toxicity data would allow prioritization of additional chemicals for biomonitoring in ECHO. There is a growing body of animal and in vitro data that suggest exogenous chemical exposures, endogenous physiological changes, and genetic regulation may together heighten susceptibility to some chemicals and increase pregnant women's health risks (Varshavsky et al 2019). Furthermore, the susceptibility of infants and children to chemicals may vary considerably, depending on factors such as the age of the child because changes occur in organ size, structure, and function from infancy through puberty (Bruckner 2000), all affecting the toxicokinetics and toxicodynamics of chemicals.…”

Section: Data Gaps Opportunities For Research and Limitationsmentioning

confidence: 99%

Identifying and Prioritizing Chemicals with Uncertain Burden of Exposure: Opportunities for Biomonitoring and Health-Related Research

Pellizzari

Woodruff

Boyles

et al. 2019

Environ Health Perspect

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BACKGROUND: The National Institutes of Health's Environmental influences on Child Health Outcomes (ECHO) initiative aims to understand the impact of environmental factors on childhood disease. Over 40,000 chemicals are approved for commercial use. The challenge is to prioritize chemicals for biomonitoring that may present health risk concerns. OBJECTIVES: Our aim was to prioritize chemicals that may elicit child health effects of interest to ECHO but that have not been biomonitored nationwide and to identify gaps needing additional research. METHODS: We searched databases and the literature for chemicals in environmental media and in consumer products that were potentially toxic. We selected chemicals that were not measured in the National Health and Nutrition Examination Survey. From over 700 chemicals, we chose 155 chemicals and created eight chemical panels. For each chemical, we compiled biomonitoring and toxicity data, U.S. Environmental Protection Agency exposure predictions, and annual production usage. We also applied predictive modeling to estimate toxicity. Using these data, we recommended chemicals either for biomonitoring, to be deferred pending additional data, or as low priority for biomonitoring. RESULTS: For the 155 chemicals, 97 were measured in food or water, 67 in air or house dust, and 52 in biospecimens. We found in vivo endocrine, developmental, reproductive, and neurotoxic effects for 61, 74, 47, and 32 chemicals, respectively. Eighty-six had data from high-throughput in vitro assays. Positive results for endocrine, developmental, neurotoxicity, and obesity were observed for 32, 11, 35, and 60 chemicals, respectively. Predictive modeling results suggested 90% are toxicants. Biomarkers were reported for 76 chemicals. Thirty-six were recommended for biomonitoring, 108 deferred pending additional research, and 11 as low priority for biomonitoring. DISCUSSION: The 108 deferred chemicals included those lacking biomonitoring methods or toxicity data, representing an opportunity for future research. Our evaluation was, in general, limited by the large number of unmeasured or untested chemicals.

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Section: Data Gaps Opportunities For Research and Limitationsmentioning

confidence: 99%

Identifying and Prioritizing Chemicals with Uncertain Burden of Exposure: Opportunities for Biomonitoring and Health-Related Research

Pellizzari

Woodruff

Boyles

et al. 2019

Environ Health Perspect

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“…More recently, many researchers began studying more deeply the outcomes that chemicals, widely distributed in the environment, may have on the health status of both the mother [8] and the fetus [9].…”

Section: Introductionmentioning

confidence: 99%

Endocrine-Disrupting Chemicals in Human Fetal Growth

Street

Bernasconi

2020

IJMS

113

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Fetal growth is regulated by a complex interaction of maternal, placental, and fetal factors. The effects and outcomes that chemicals, widely distributed in the environment, may have on the health status of both the mother and the fetus are not yet well defined. Mainly mixtures of chemical substances are found in the mothers and placenta. Exposure to endocrine-disrupting chemicals (EDCs) can be associated with fetal growth retardation, thyroid dysfunction, and neurological disorders. EDCs mostly interfere with insulin, glucocorticoid, estrogenic, and thyroid pathways, with subsequent effects on normal endocrine and metabolic functions, which cause changes in the epigenome and state of inflammation with life-long effects and consequences. International scientific societies recommend the implementation of research and of all possible preventive measures. This review briefly summarizes all these aspects.

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“…Furthermore, given the increasingly recognized importance of the maternal nutritional, mental and emotional states, the rise in women exposed to harmful environmental and chemical exposures during their pregnancies and the profound impacts these can have on the pregnancy and the future health of the child ( Hoirisch-Clapauch et al , 2015 ; Lewis et al , 2015 ; Unger et al , 2016 ; Chen et al , 2018 ; Henschke, 2019 ; Varshavsky et al , 2019 ), their effects on the placenta are all deserving of further investigation, so as to increase ways of promoting benefits of some lifestyles while minimizing adversity. Pre-existing medical conditions (e.g.…”

Section: Knowledge Gaps and Future Directionsmentioning

confidence: 99%

Current approaches and developments in transcript profiling of the human placenta

Yong

Chan

2020

Human Reproduction Update

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BACKGROUND The placenta is the active interface between mother and foetus, bearing the molecular marks of rapid development and exposures in utero. The placenta is routinely discarded at delivery, providing a valuable resource to explore maternal-offspring health and disease in pregnancy. Genome-wide profiling of the human placental transcriptome provides an unbiased approach to study normal maternal–placental–foetal physiology and pathologies. OBJECTIVE AND RATIONALE To date, many studies have examined the human placental transcriptome, but often within a narrow focus. This review aims to provide a comprehensive overview of human placental transcriptome studies, encompassing those from the cellular to tissue levels and contextualize current findings from a broader perspective. We have consolidated studies into overarching themes, summarized key research findings and addressed important considerations in study design, as a means to promote wider data sharing and support larger meta-analysis of already available data and greater collaboration between researchers in order to fully capitalize on the potential of transcript profiling in future studies. SEARCH METHODS The PubMed database, National Center for Biotechnology Information and European Bioinformatics Institute dataset repositories were searched, to identify all relevant human studies using ‘placenta’, ‘decidua’, ‘trophoblast’, ‘transcriptome’, ‘microarray’ and ‘RNA sequencing’ as search terms until May 2019. Additional studies were found from bibliographies of identified studies. OUTCOMES The 179 identified studies were classifiable into four broad themes: healthy placental development, pregnancy complications, exposures during pregnancy and in vitro placental cultures. The median sample size was 13 (interquartile range 8–29). Transcriptome studies prior to 2015 were predominantly performed using microarrays, while RNA sequencing became the preferred choice in more recent studies. Development of fluidics technology, combined with RNA sequencing, has enabled transcript profiles to be generated of single cells throughout pregnancy, in contrast to previous studies relying on isolated cells. There are several key study aspects, such as sample selection criteria, sample processing and data analysis methods that may represent pitfalls and limitations, which need to be carefully considered as they influence interpretation of findings and conclusions. Furthermore, several areas of growing importance, such as maternal mental health and maternal obesity are understudied and the profiling of placentas from these conditions should be prioritized. WIDER IMPLICATIONS Integrative analysis of placental transcriptomics with other ‘omics’ (methylome, proteome and metabolome) and linkage with future outcomes from longitudinal studies is crucial in enhancing knowledge of healthy placental development and function, and in enabling the underlying causal mechanisms of pregnancy complications to be identified. Such understanding could help in predicting risk of future adversity and in designing interventions that can improve the health outcomes of both mothers and their offspring. Wider collaboration and sharing of placental transcriptome data, overcoming the challenges in obtaining sufficient numbers of quality samples with well-defined clinical characteristics, and dedication of resources to understudied areas of pregnancy will undoubtedly help drive the field forward.

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Heightened susceptibility: A review of how pregnancy and chemical exposures influence maternal health

Cited by 116 publications

References 193 publications

Identifying and Prioritizing Chemicals with Uncertain Burden of Exposure: Opportunities for Biomonitoring and Health-Related Research

Identifying and Prioritizing Chemicals with Uncertain Burden of Exposure: Opportunities for Biomonitoring and Health-Related Research

Endocrine-Disrupting Chemicals in Human Fetal Growth

Current approaches and developments in transcript profiling of the human placenta

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