Human placenta: a human organ for developmental toxicology research and biomonitoring

Myllynen, Päivi; Pasanen, Markku; Pelkonen, Olavi

doi:10.1016/j.placenta.2004.09.006

Cited by 219 publications

(143 citation statements)

References 128 publications

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“…Although much of this development has occurred after the embryo's neural tube has closed, the continuum of development from the trophoblast to the placenta proper makes this a reasonable surrogate in which environmental exposures that occurred earlier in gestation can be evaluated. Thus, placental levels of pollutants of interest can be used as biomarkers of early in utero exposures even before the embryo proper is established (17). Possible associations between PAH exposure and the risk of NTDs have been reported in several previously published epidemiological studies.…”

Section: Discussionmentioning

confidence: 99%

Association of selected persistent organic pollutants in the placenta with the risk of neural tube defects

Ren

Qiu

Jin

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

261

169

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Persistent organic pollutants (POPs) have been associated with a wide range of adverse health effects. Our case-control study was performed to explore the association between placental levels of selected POPs and risks for neural tube defects (NTDs) in a Chinese population with a high prevalence of NTDs. Cases included 80 fetuses or newborns with NTDs, whereas the controls were 50 healthy, nonmalformed newborn infants. Placental concentrations of polycyclic aromatic hydrocarbons (PAHs), organochlorine pesticides, polychlorinated biphenyls, and polybrominated diphenyl ethers were analyzed by gas chromatography-mass spectrometry. The medians of PAHs, o,p′-isomers of dichlorodiphenyltrichloroethane (DDT) and metabolites, α-and γ-hexachlorocyclohexane (HCH), and α-endosulfan were significantly higher in case placentas than in controls. PAH concentrations above the median were associated with a 4.52-fold [95% confidence interval (CI), 2.10-9.74) increased risk for any NTDs, and 5.84-(95% CI, 2.28-14.96) and 3.71-fold (95% CI, 1.57-8.79) increased risks for anencephaly and spina bifida, respectively. A dose-response relationship was observed between PAH levels and the risk of NTDs, with odds ratios for the second, third, and fourth quartiles, compared with the first, of 1.77-(95% CI, 0.66-4.76), 3.83-(95% CI, 1.37-10.75), and 11.67-fold (95% CI, 3.28-41.49), respectively. A dose-response relationship was observed for anencephaly and spina bifida subtypes. Similar results were observed for o,p′-DDT and metabolites, α-HCH, γ-HCH, and α-endosulfan, whereas no dose-response relationship was observed for the last two pollutants. Elevated placental concentrations of PAHs, o,p′-DDT and metabolites, and α-HCH were associated with increased risks of NTDs in this population.congenital abnormalities | indoor air pollution

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Section: Discussionmentioning

confidence: 99%

Association of selected persistent organic pollutants in the placenta with the risk of neural tube defects

Ren

Qiu

Jin

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

261

169

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“…Although placental CYPs are capable of metabolizing several xenobiotic compounds at term [135,136] , only a few of these enzymes are actually functionally active [137,138] . Moreover, the abundance of some of these CYPs has been shown to be affected by exposure to xenobiotics, as occurs in tobacco-smoking pregnant women [138,139] . Other phaseⅠmetabolizing enzymes such as aldehyde dehydrogenases (ALDHs) participate in the detoxification of endogenous and exogenous compounds, including ethanol.…”

Section: Metabolic Barriermentioning

confidence: 99%

Excretion of biliary compounds during intrauterine life

Macı́as¹,

Marin²,

Serrano³

2009

WJG

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In adults, the hepatobiliary system, together with the kidney, constitute the main routes for the elimination of several endogenous and xenobiotic compounds into bile and urine, respectively. However, during intrauterine life the biliary route of excretion for cholephilic compounds, such as bile acids and biliary pigments, is very poor. Although very early in pregnancy the fetal liver produces bile acids, bilirubin and biliverdin, these compounds cannot be efficiently eliminated by the fetal hepatobiliary system, owing to the immaturity of the excretory machinery in the fetal liver. Therefore, the potentially harmful accumulation of cholephilic compounds in the fetus is prevented by their elimination across the placenta. Owing to the presence of detoxifying enzymes and specific transport systems at different locations of the placental barrier, such as the endothelial cells of chorionic vessels and trophoblast cells, this organ plays an important role in the hepatobiliary-like function during intrauterine life. The relevance of this excretory function in normal fetal physiology is evident in situations where high concentrations of biliary compounds are accumulated in the mother. This may result in oxidative stress and apoptosis, mainly in the placenta and fetal liver, which might affect normal fetal development and challenge the fate of the pregnancy. The present article reviews current knowledge of the mechanisms underlying the hepatobiliary function of the fetal-placental unit and the repercussions of several pathological conditions on this tandem.

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“…Recent literature indicates that low-level exposure to environmental contaminants may indeed interfere with placental function (Myllynen et al 2005;Mose et al 2006;Sagiv et al 2007). For example, endosulfan inhibits aromatase activity; whereas, methomyl, pirimicarb, propamocarb, iprodion, lindane and bisphenol-A enhance placental aromatase activity (Nativelle-Serpentini et al 2003).…”

Section: Introductionmentioning

confidence: 99%

“…For example, endosulfan inhibits aromatase activity; whereas, methomyl, pirimicarb, propamocarb, iprodion, lindane and bisphenol-A enhance placental aromatase activity (Nativelle-Serpentini et al 2003). TCDD exposure is associated with fetus loss and the alteration of the secretion of chorionic gonadotropin hormone in primates (Guo et al 1999;Chen et al 2003;Myllynen et al 2005). With regards to chlorpyrifos, CPF and/or its metabolites have been detected in the fetuses of dams administered CPF perinatally (Mattsson et al 2000;Abdel-Rahman et al 2002).…”

Section: Introductionmentioning

confidence: 99%

Characterization of chlorpyrifos-induced apoptosis in placental cells

Saulsbury¹,

Heyliger²,

Wang³

et al. 2008

Toxicology

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The mechanism by which chlorpyrifos exerts its toxicity in fetal and perinatal animals has yet to be elucidated. Since the placenta is responsible for transport of nutrients and is a major supplier hormones to the fetus, exposure to xenobiotics that alter the function or viability of placenta cells could ostensibly alter the development of the fetus. In this study, JAR cells were used to determine if CPF and the metabolites 3,5,6-trichloro-2-pyridinol (TCP) and chlorpyrifos-oxon (CPO) are toxic to the placenta. Our results indicate that chlorpyrifos (CPF), and its metabolite chlorpyrifos-oxon (CPO) caused a dose-dependent reduction in cellular viability with CPF being more toxic than its metabolites. Chlorpyrifos-induced toxicity was characterized by the loss of mitochondrial potential, the appearance of nuclear condensation and fragmentation, down-regulation of Bcl-2 as well as upregulation of TNFα and FAS mRNA. Pharmacological inhibition of FAS, nicotinic and TNF-α receptors did not attenuate CPF-induced toxicity. Atropine exhibited minimal ability to reverse toxicity. Furthermore, signal transduction inhibitors PD98059, SP600125, LY294002 and U0126 failed to attenuate toxicity; however, SB202190 (inhibitor of p38α and p38β MAPK) sensitized cells to CPF-induced toxicity. Pan-caspase inhibitor Q-VD-OPh produced a slight but significant reversal of CPF-induced toxicity indicating that the major caspase pathways are not integral to CPF-induced toxicity. Taken collectively, these results suggest that chlorpyrifos induces apoptosis in placental cells through pathways not dependent on FAS/TNF signaling, activation of caspases or inhibition of cholinesterase. In addition, our data further indicates that activation of p38 MAPK is integral to the protection cells against CPF-induced injury.

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Human placenta: a human organ for developmental toxicology research and biomonitoring

Cited by 219 publications

References 128 publications

Association of selected persistent organic pollutants in the placenta with the risk of neural tube defects

Association of selected persistent organic pollutants in the placenta with the risk of neural tube defects

Excretion of biliary compounds during intrauterine life

Characterization of chlorpyrifos-induced apoptosis in placental cells

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