Deleterious effects of polynuclear aromatic hydrocarbon on blood vascular system of the rat fetus

Sanyal, Mrinal K.; Li, You-Lan

doi:10.1002/bdrb.20122

Cited by 28 publications

(13 citation statements)

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“…In addition, PAHs may act directly on the embryo to negatively affect its growth. Certainly PAHs are able to cross the perfused human placenta in vitro (30), and high doses given to pregnant rats cause fetal vascular hemorrhage (49). These results suggest that PAH exposure can have direct fetal effects.…”

Section: Discussionmentioning

confidence: 97%

Vessel tortuousity and reduced vascularization in the fetoplacental arterial tree after maternal exposure to polycyclic aromatic hydrocarbons

Rennie

Detmar

Whiteley

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants and the main toxicants found in cigarettes. Women are often exposed to PAHs before pregnancy, typically via prepregnancy smoking. To determine how prepregnancy exposure affects the fetoplacental vasculature of the placenta, we exposed female mice to PAHs before conception, perfused the fetoplacental arterial trees with X-ray contrast agent, and imaged the vasculature ex vivo by microcomputed tomography (micro-CT) at embryonic day 15.5. Automated vascular segmentation and flow calculations revealed that in control trees, <40 chorionic plate vessels (diameter>180 μm) gave rise to ∼1,300 intraplacental arteries (50-180 μm), predicting an arterial vascular resistance of 0.37±0.04 mmHg·s·μl(-1). PAH exposure increased vessel curvature of chorionic plate vessels and significantly increased the tortuousity ratio of the tree. Intraplacental arteries were reduced by 17%, primarily due to a 27% decrease in the number of arteriole-sized (50-100 μm) vessels. There were no changes in the number of chorionic vessels, the depth or span of the tree, the diameter scaling coefficient, or the segment length-to-diameter ratio. PAH exposure resulted in a tree with a similar size and dichotomous branching structure, but one that was comparatively sparse so that arterial vascular resistance was increased by 30%. Assuming the same pressure gradient, blood flow would be 19% lower. Low flow may contribute to the 23% reduction observed in fetal weight. New insights into the specific effects of PAH exposure on a developing arterial tree were achieved using micro-CT imaging and automated vascular segmentation analysis.

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Section: Discussionmentioning

confidence: 97%

Vessel tortuousity and reduced vascularization in the fetoplacental arterial tree after maternal exposure to polycyclic aromatic hydrocarbons

Rennie

Detmar

Whiteley

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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“…Developmental and reproductive toxicity due to prenatal exposure to PAHs and similar AhR ligands has been observed in various animal species (Pocar et al 2005; Sanyal and Li 2007). …”

Section: Discussionmentioning

confidence: 99%

Bulky DNA Adducts in Cord Blood, Maternal Fruit-and-Vegetable Consumption, and Birth Weight in a European Mother–Child Study (NewGeneris)

Pedersen

Schoket

Godschalk

et al. 2013

Environ Health Perspect

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Background: Tobacco-smoke, airborne, and dietary exposures to polycyclic aromatic hydrocarbons (PAHs) have been associated with reduced prenatal growth. Evidence from biomarker-based studies of low-exposed populations is limited. Bulky DNA adducts in cord blood reflect the prenatal effective dose to several genotoxic agents including PAHs.Objectives: We estimated the association between bulky DNA adduct levels and birth weight in a multicenter study and examined modification of this association by maternal intake of fruits and vegetables during pregnancy.Methods: Pregnant women from Denmark, England, Greece, Norway, and Spain were recruited in 2006–2010. Adduct levels were measured by the 32P-postlabeling technique in white blood cells from 229 mothers and 612 newborns. Maternal diet was examined through questionnaires.Results: Adduct levels in maternal and cord blood samples were similar and positively correlated (median, 12.1 vs. 11.4 adducts in 108 nucleotides; Spearman rank correlation coefficient = 0.66, p < 0.001). Cord blood adduct levels were negatively associated with birth weight, with an estimated difference in mean birth weight of –129 g (95% CI: –233, –25 g) for infants in the highest versus lowest tertile of adducts. The negative association with birth weight was limited to births in Norway, Denmark, and England, the countries with the lowest adduct levels, and was more pronounced in births to mothers with low intake of fruits and vegetables (–248 g; 95% CI: –405, –92 g) compared with those with high intake (–58 g; 95% CI: –206, 90 g)Conclusions: Maternal exposure to genotoxic agents that induce the formation of bulky DNA adducts may affect intrauterine growth. Maternal fruit and vegetable consumption may be protective.Citation: Pedersen M, Schoket B, Godschalk RW, Wright J, von Stedingk H, Törnqvist M, Sunyer J, Nielsen JK, Merlo DF, Mendez MA, Meltzer HM, Lukács V, Landström A, Kyrtopoulos SA, Kovács K, Knudsen LE, Haugen M, Hardie LJ, Gützkow KB, Fleming S, Fthenou E, Farmer PB, Espinosa A, Chatzi L, Brunborg G, Brady NJ, Botsivali M, Arab K, Anna L, Alexander J, Agramunt S, Kleinjans JC, Segerbäck D, Kogevinas M. 2013. Bulky DNA adducts in cord blood, maternal fruit-and-vegetable consumption, and birth weight in a European mother–child study (NewGeneris). Environ Health Perspect 121:1200–1206; http://dx.doi.org/10.1289/ehp.1206333

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“…“brain spared”) scored significantly lower in neurodevelopmental tests, intelligence quotient, and school performance [30]. In a murine model, fetal cranium and neural tissues are most exquisitely sensitive to PAHs during the period of organogenesis [31]. Accordingly, we speculated that onset of PAH-mediated impairment in fetal neural tissues occurs in late first to early second trimester.…”

Section: Methodsmentioning

confidence: 99%

Fetal Window of Vulnerability to Airborne Polycyclic Aromatic Hydrocarbons on Proportional Intrauterine Growth Restriction

Choi¹,

Wang

Lin

et al. 2012

PLoS ONE

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BackgroundAlthough the entire duration of fetal development is generally considered a highly susceptible period, it is of public health interest to determine a narrower window of heightened vulnerability to polycyclic aromatic hydrocarbons (PAHs) in humans. We posited that exposure to PAHs during the first trimester impairs fetal growth more severely than a similar level of exposure during the subsequent trimesters.MethodsIn a group of healthy, non-smoking pregnant women with no known risks of adverse birth outcomes, personal exposure to eight airborne PAHs was monitored once during the second trimester for the entire cohort (n = 344), and once each trimester within a subset (n = 77). Both air monitoring and self-reported PAH exposure data were used in order to statistically estimate PAH exposure during the entire gestational period for each individual newborn.ResultsOne natural-log unit increase in prenatal exposure to the eight summed PAHs during the first trimester was associated with the largest decrement in the Fetal Growth Ratio (FGR) (−3%, 95% Confidence Interval (CI), −5 to −0%), birthweight (−105 g, 95% CI, −188 to −22 g), and birth length (−0.78 cm, 95% CI, −1.30 to −0.26 cm), compared to the unit effects of PAHs during the subsequent trimesters, after accounting for confounders. Furthermore, a unit exposure during the first trimester was associated with the largest elevation in Cephalization Index (head to weight ratio) (3 μm/g, 95% CI, 1 to 5 μm/g). PAH exposure was not associated with evidence of asymmetric growth restriction in this cohort.ConclusionPAH exposure appears to exert the greatest adverse effect on fetal growth during the first trimester. The present data support the need for the protection of pregnant women and the embryo/fetus, particularly during the earliest stage of pregnancy.

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Deleterious effects of polynuclear aromatic hydrocarbon on blood vascular system of the rat fetus

Abstract: Maternal PAH exposure induced placental toxicity and associated adverse fetal development and hemorrhage in different parts of the fetal body, in particular, marked intradermal and cranial hemorrhage, showing that developing fetal blood vasculature is a target of PAH toxicity.

Cited by 28 publications

References 64 publications

Vessel tortuousity and reduced vascularization in the fetoplacental arterial tree after maternal exposure to polycyclic aromatic hydrocarbons

Vessel tortuousity and reduced vascularization in the fetoplacental arterial tree after maternal exposure to polycyclic aromatic hydrocarbons

Bulky DNA Adducts in Cord Blood, Maternal Fruit-and-Vegetable Consumption, and Birth Weight in a European Mother–Child Study (NewGeneris)

Fetal Window of Vulnerability to Airborne Polycyclic Aromatic Hydrocarbons on Proportional Intrauterine Growth Restriction

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