Toxicology of the Placenta

Gupta, Ramesh C.

doi:10.1002/9780470744307.gat088

Cited by 10 publications

(3 citation statements)

References 166 publications

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“…Anticholinesterase pesticides and heavy metals have been shown to cross the placental barrier, and both classes of environmental contaminants individually have been extensively investigated for reproductive and developmental toxicity in a variety of animal species (Gupta, 2007(Gupta, , 2009Pelkonen et al, 2006). Despite being aware that concurrent or sequential exposure of humans and animals to pesticides and metals is a reality, very little data are available on the potential developmental toxicity of combined exposures to these chemicals.…”

Section: Developmental Toxicitymentioning

confidence: 99%

Interaction of Anticholinesterase Pesticides with Metals

Malik

Telang

Kumar

et al. 2011

Anticholinesterase Pesticides

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Section: Developmental Toxicitymentioning

confidence: 99%

Interaction of Anticholinesterase Pesticides with Metals

Malik

Telang

Kumar

et al. 2011

Anticholinesterase Pesticides

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“…The placenta is one of the least understood human organs and perturbations in cell growth and signaling can disrupt temporally sequenced developmental processes in the developing fetus and result in long-term functional deficits and detrimental health impacts for offspring. A challenge with studying placental transport using laboratory animals is the inter-species variation which can make the translational aspects of animal studies to human health outcome complicated (as reviewed in literature 12–15 ). The ex vivo human placenta perfusion model addresses several of these challenges; however, the perfusion model require access to human placental tissue and a sophisticated instrumental setup which makes it challenging to use for comparison studies of multiple individual and mixture of compounds.…”

Section: Introductionmentioning

confidence: 99%

Placental trophoblast transfer of opioids following exposures to individual or mixtures of opioids in vitro

Mortensen

Caffaro

Snyder

et al. 2019

Exp Biol Med (Maywood)

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Infants born with neonatal abstinence syndrome increased 5-fold between 2000 and 2012. Prenatal exposure to opioids has been linked to altered brain development, congenital heart defects, neural tube defects, and clubfoot. In the study presented here, placental transfer rate of six opioids; morphine, heroin, fentanyl, methadone, oxycodone, and naloxone was compared in vitro using a human trophoblast cell monolayer model, BeWo b30. The rate and concentration of opioid translocation were investigated individually and in mixtures. The opioid transfer was quantified at 5, 15, 30, 60, and 120 min, using target liquid chromatography-mass spectrometry. The transfer was lowest for heroin (<1.2% of administered dose at 120 min; the permeability across the cells [P]: 0.21 × 10−5 cm/s) and highest for oxycodone (13.2% of administered dose at 120 min; P: 2.46 × 10−5 cm/s). As oxycodone is a preferred drug for both short- and long-term pain treatment, more knowledge is needed to understand the potential adverse impact on fetal development, growth, and well-being. Opioid exposure is likely to happen as mixtures, and we therefore investigated the transfer of selected mixtures. Permeability was significantly decreased for heroin when administered together with fentanyl. This study demonstrates that the transfer rate between individual opioids varies significantly and that some mixtures may impact the transfer of some individual opioids like heroin. Impact statement Gaining knowledge about opioid exposure and placental transfer of opioids is an important part of providing clinicians with the necessary information for therapeutic strategies during pregnancy in the rising opioid epidemic. Opioids exposure often includes a mixture rather than an exposure to an individual opioid. We investigated placental trophoblast permeability to opioids in vitro for six individual opioids and selected mixtures. The rate and concentration of opioid translocation across placental trophoblast monolayer varied considerably between the six investigated opioids. Oxycodone had the highest level of translocation. We also found that the transfer of heroin decreased when administered together with fentanyl, while no change was observed for fentanyl transfer in the mixture. This suggests that opioid mixtures may decrease translocation of some opioids while others are unaffected.

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“…1 The placenta is formed by both fetal (chorionic plate and chorionic villi) and maternal (decidua basalis) tissues. The fetal placenta consists of syncytiotrophoblast and cytotrophoblast (or Langerhans) layers.…”

Section: Introductionmentioning

confidence: 99%

Fetal polymorphisms at the ABCB1-transporter gene locus are associated with susceptibility to non-syndromic oral cleft malformations

et al. 2013

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ATP-binding cassette (ABC) proteins in the placenta regulate fetal exposure to xenobiotics. We hypothesized that functional polymorphisms in ABC genes influence risk for non-syndromic oral clefts (NSOC). Both family-based and case-control studies were undertaken to evaluate the association of nine potentially functional single-nucleotide polymorphisms within four ABC genes with risk of NSOC. Peripheral blood DNA from a total of 150 NSOC case-parent trios from Singapore and Taiwan were genotyped, as was cord blood DNA from 189 normal Chinese neonates used as controls. In trios, significant association was observed between the ABCB1 single-nucleotide polymorphisms and NSOC (Po0.05). Only ABCB1 rs1128503 retained significant association after Bonferroni correction (odds ratio (OR) ¼ 2.04; 95% confidence interval (CI) ¼ 1.42-2.98), while rs2032582 and rs1045642 showed nominal significance. Association with rs1128503 was replicated in a case-control analysis comparing NSOC probands with controls (OR ¼ 1.58; 95% CI ¼ 1.12-2.23). A comparison between the mothers of probands and controls showed no evidence of association, suggesting NSOC risk is determined by fetal and not maternal ABCB1 genotype. The two studies produced a combined OR of 1.79 (95% CI ¼ 1.38-2.30). The T-allele at rs1128503 was associated with higher risk. This study thus provides evidence that potentially functional polymorphisms in fetal ABCB1 modulate risk for NSOC, presumably through suboptimal exclusion of xenobiotics at the fetal-maternal interface.

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Toxicology of the Placenta

Cited by 10 publications

References 166 publications

Interaction of Anticholinesterase Pesticides with Metals

Interaction of Anticholinesterase Pesticides with Metals

Placental trophoblast transfer of opioids following exposures to individual or mixtures of opioids in vitro

Fetal polymorphisms at the ABCB1-transporter gene locus are associated with susceptibility to non-syndromic oral cleft malformations

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