Fetal growth restriction triggered by polycyclic aromatic hydrocarbons is associated with altered placental vasculature and <i>AhR</i>-dependent changes in cell death

Detmar, Jacqui; Rennie, Monique Y.; Whiteley, Kathie J.; Qu, Dawei; Taniuchi, Yoshinari; Shang, Xueyuan; Casper, Robert F.; Adamson, S. Lee; Sled, John G.; Jurisicova, Andrea

doi:10.1152/ajpendo.90436.2008

Cited by 72 publications

(65 citation statements)

References 87 publications

(88 reference statements)

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“…In a study where exposure to polycyclic aromatic hydrocarbons (PAHs, a contaminant found in air pollution) was monitored in pregnant women, increased PAH exposure during the first trimester increased the risk for fetal growth ratio reduction (7). This was confirmed in controlled animal studies where exposure to PAH altered placental vasculature, increased apoptotic markers during gestation, and reduced survival of resultant adult mice (11). Prenatal exposure to environmental sidestream tobacco smoke has also been shown to increase atherogenesis, superoxide dismutase activity, and mitochondrial damage in the heart tissue of mice (48), as well as increase blood pressure reactivity in humans (8).…”

Section: -Exposed Mice (B) C: End-systolic Volume (Esv) D: Enddiasmentioning

confidence: 90%

Early life exposure to air pollution induces adult cardiac dysfunction

Gorr

Velten²,

Nelin

et al. 2014

American Journal of Physiology-Heart and Circulatory Physiology

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Exposure to ambient air pollution contributes to the progression of cardiovascular disease, particularly in susceptible populations. The objective of the present study was to determine whether early life exposure to air pollution causes persistent cardiovascular consequences measured at adulthood. Pregnant FVB mice were exposed to filtered (FA) or concentrated ambient particulate matter (PM2.5) during gestation and nursing. Mice were exposed to PM2.5 at an average concentration of 51.69 μg/m3 from the Columbus, OH region for 6 h/day, 7 days/wk in utero until weaning at 3 wk of age. Birth weight was reduced in PM2.5 pups compared with FA (1.36 ± 0.12 g FA, n = 42 mice; 1.30 ± 0.15 g PM2.5, n = 67 P = 0.012). At adulthood, mice exposed to perinatal PM2.5 had reduced left ventricular fractional shortening compared with FA-exposed mice (43.6 ± 2.1% FA, 33.2 ± 1.6% PM2.5, P = 0.001) with greater left ventricular end systolic diameter. Pressure-volume loops showed reduced ejection fraction (79.1 ± 3.5% FA, 35.5 ± 9.5% PM2.5, P = 0.005), increased end-systolic volume (10.4 ± 2.5 μl FA, 39.5 ± 3.8 μl PM2.5, P = 0.001), and reduced dP/d t maximum (11,605 ± 200 μl/s FA, 9,569 ± 800 μl/s PM2.5, P = 0.05) and minimum (−9,203 ± 235 μl/s FA, −7,045 ± 189 μl/s PM2.5, P = 0.0005) in PM2.5-exposed mice. Isolated cardiomyocytes from the hearts of PM2.5-exposed mice had reduced peak shortening (%PS, 8.53 ± 2.82% FA, 6.82 ± 2.04% PM2.5, P = 0.003), slower calcium reuptake (τ, 0.22 ± 0.09 s FA, 0.26 ± 0.07 s PM2.5, P = 0.048), and reduced response to β-adrenergic stimulation compared with cardiomyocytes isolated from mice that were exposed to FA. Histological analyses revealed greater picro-sirius red-positive-stained areas in the PM2.5 vs. FA group, indicative of increased collagen deposition. We concluded that these data demonstrate the detrimental role of early life exposure to ambient particulate air pollution in programming of adult cardiovascular diseases and the potential for PM2.5 to induce persistent cardiac dysfunction at adulthood.

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Section: -Exposed Mice (B) C: End-systolic Volume (Esv) D: Enddiasmentioning

confidence: 90%

Early life exposure to air pollution induces adult cardiac dysfunction

Gorr

Velten²,

Nelin

et al. 2014

American Journal of Physiology-Heart and Circulatory Physiology

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“…Using two different mouse strains chronically exposed to PAHs prior to conception, we were able to recapitulate a number of conditions observed in women smokers [Cnattingius 2004;Gruslin et al 2001;Higgins 2002;Shiverick and Salafia 1999]. Exposure to PAHs using inbred, C57Bl/6 mice included alterations in placental vasculature, IUGR and altered cell death patterns observed in C57Bl/6 mice [Detmar et al 2008], whereas outbred ICR mice exhibited increased rates of spontaneous abortion [Detmar et al 2006]. In addition to providing information regarding tobacco use during pregnancy, we pose that this would be a valuable experimental model in which to assess the effects of gestational exposure to environmental pollutants, many of which trigger the AhR pathway (reviewed in [Pocar et al 2005]) and lead to deleterious gestational outcomes [Cnattingius 2004;Sharara et al 1998;Sram 1999] similar to that seen in smoking mothers.…”

Section: Chronic Exposure To Pahsmentioning

confidence: 94%

Embryonic Resorption and Polycyclic Aromatic Hydrocarbons: Putative Immune-mediated Mechanisms

Detmar

Jurisicova

2010

Systems Biology in Reproductive Medicine

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Polycyclic aromatic hydrocarbons (PAHs) are released into the environment as a result of incomplete fossil fuel combustion from industrial furnaces, woodburning stoves, and automobile exhaust fumes; however, the primary source of human exposure to these compounds is cigarette smoke. Embryonic and fetal loss after treatment with high doses of PAHs have been well documented in animal studies; however, few studies have addressed the reproductive consequences of long-term, low-level exposure to these chemicals. We previously reported that low doses of PAHs administered to ICR mice over a period of 9 weeks prior to conception resulted in early embryonic resorptions, whereby treated dams lost approximately 50% of their litter. During the course of these studies, we observed greater numbers of infiltrating uterine natural killer (uNK) cells into the placenta of PAH-exposed conceptuses. While exposure to high levels of PAHs has been shown to be immunosuppressive, increasing evidence suggests that chronic, low-dose exposure to PAHs may stimulate immune cells. Thus, we hypothesized that low-dose, chronic PAH exposure in our mouse model is mediating embryonic resorption by hyperstimulating maternal immune cells. In this review of the literature, we outline the rationale of our argument and present preliminary data, focussing upon PAH-mediated alterations in uNK cell dynamics and how these changes may be linked to early embryonic resorptions.

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“…Thus, prepregnancy smoking and/or PAH exposure may cause defects in larger vessels, thereby contributing to increased fetoplacental vascular resistance and resulting in reduced fetal growth. Indeed, exposure to PAHs before pregnancy in mice reduced the volume and surface area of the fetoplacental arterial tree (vessels Ͼ30 m), whereas veins appeared unaffected (14). Thus, as observed in smoking mothers (1,21,36), fetoplacental vascular resistance may be elevated, and this would be anticipated to reduce fetoplacental blood flow thereby contributing to fetal growth restriction.…”

mentioning

confidence: 98%

“…In mouse models, prepregnancy exposure to PAHs (14) or environmental air pollutants (55) results in an apparent increase in fetoplacental capillaries that contrasts with decreased capillarization in the placentas of smoking mothers (8,25). Nevertheless, fetal growth restriction is observed as a consequence of exposure whether before or during pregnancy.…”

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confidence: 99%

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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Fetal growth restriction triggered by polycyclic aromatic hydrocarbons is associated with altered placental vasculature and AhR-dependent changes in cell death

Abstract: growth restriction triggered by polycyclic aromatic hydrocarbons is associated with altered placental vasculature and AhR-dependent changes in cell death.

Cited by 72 publications

References 87 publications

Early life exposure to air pollution induces adult cardiac dysfunction

Early life exposure to air pollution induces adult cardiac dysfunction

Embryonic Resorption and Polycyclic Aromatic Hydrocarbons: Putative Immune-mediated Mechanisms

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

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