Exposure to Ambient Particulate Matter during Specific Gestational Periods Produces Adverse Obstetric Consequences in Mice

Abstract

Background:Epidemiological studies associate inhalation of fine-sized particulate matter (PM2.5) during pregnancy with preterm birth (PTB) and low birth weight (LBW) but disagree over which time frames are most sensitive, or if effects are cumulative.Objectives:Our objective was to provide experimental plausibility for epidemiological observations by testing the hypothesis that exposure to PM2.5 during discrete periods of pregnancy results in PTB and LBW.Methods:For the first study, timed-pregnant B6C3normalF1 mice were exposed to concentrated ambient PM2.5 (CAPs) or filtered air (FA) throughout pregnancy [6 h/d from gestational day (GD) 0.5 through GD16.5]. A follow-up study examined the effects of CAPs exposure during discrete gestational periods (1: GD0.5–5.5; 2: GD6.5–14.5; 3: GD14.5–16.5; 4: GD0.5–16.5) aligning to milestones during human development.Results:In the first experiment, exposure to 160 μg CAPs/m3 throughout pregnancy decreased gestational term by 0.5 d (∼1.1 wk decrease for humans) and birth weight by 11.4% compared with FA. The follow-up experiment investigated timing of CAPs exposure (mean concentrations at 178, 193, 171, and 173 μg/m3 for periods 1–4, respectively). Pregnancy was significantly shortened (vs. FA) by ∼0.4d when exposure occurred during gestational periods 2 and 4, and by ∼0.5d if exposure occurred during period 3. Exposure during periods 1, 2, and 4 reduced birth weight by ∼10% compared with FA, and placental weight was reduced (∼8%) on GD17.5 if exposure occurred only during period 3.Conclusions:Adverse PM2.5-induced outcomes such as PTB and LBW are dependent upon the periods of maternal exposure. The results of these experimental studies could contribute significantly to air pollution policy decisions in the future. https://doi.org/10.1289/EHP1029

Enhanced cerebellar myelination with concomitant iron elevation and ultrastructural irregularities following prenatal exposure to ambient particulate matter in the mouse

“…As reported in greater detail in Klocke et al (2017) and Blum et al (2017), the concentration of CAPs experienced by the pregnant dams averaged 92.69 μg/m 3 (daily range: 32.95-184.43l μg/m 3 ) over the course of gestation and these levels did not induce overt reproductive toxicity to the dams or offspring. Air control dams experienced an average particle concentration of 3.52 ± 0.87 μg/m 3 .…”

“…This study is an extension of prior work and utilized brain tissue from previously performed air pollution exposures (Blum et al 2017; Klocke et al 2017). Briefly, 8-10 week-old male and female B6C3F1 mice were purchased from Jackson Laboratory (Bar Harbor, ME) and paired as described previously (Blum et al 2017). Females were removed from the pairing upon discovery of a vaginal plug, designated gestational day 0.5 (GD0.5).…”

“…Mass concentration and elemental composition of CAPs exposures was determined as described previously (Blum et al 2017; Klocke et al 2017). X-ray fluorescence spectroscopy (XRF) was used to determine the elemental composition of particles captured on Teflon filters within exposure chambers using an ARL QUANT’X EDXRF Analyzer (ThermoFisher Scientific, Waltham, Massachusetts).…”

Adverse organogenesis and predisposed long-term metabolic syndrome from prenatal exposure to fine particulate matter

“…Also, chronic exposure of female mice to fine PM emitted by urban transportation vehicles before and during pregnancy increased postimplantation embryonic death by 70% and reduced birth weights by 20% (11). Exposure of female mice to PM during either early gestation (days 0.5 to 5.5 or 6.5 to 14.5) or early to late gestation (days 0.5 to 16.5) reduced birth weights by the same extent (12). Also, increased susceptibility of offspring to experimentally induced heart failure was identified after female mice were exposed to diesel exhaust PM before conception as well as during gestation and early postnatal life (13).…”

“…including oxidative stress, inflammation, vascular dysfunction, and increased susceptibility to metabolic syndrome including obesity and diabetes (11)(12)(13)(14)(15)(16)(17). In addition, a recent study revealed that in utero ultrafine PM exposure leads to offspring pulmonary immunosuppression in offspring (10).…”