Early life exposure to fine particulate matter (PM) in air is associated with infant respiratory disease and childhood asthma, but limited epidemiological data exist concerning the impacts of ultrafine particles (UFPs) on the etiology of childhood respiratory disease. Specifically, the role of UFPs in amplifying Th2- and/or Th17-driven inflammation (asthma promotion) or suppressing effector T cells (increased susceptibility to respiratory infection) remains unclear. Using a mouse model of in utero UFP exposure, we determined early immunological responses to house dust mite (HDM) allergen in offspring challenged from 0 to 4 wk of age. Two mice strains were exposed throughout gestation: C57BL/6 (sensitive to oxidative stress) and BALB/C (sensitive to allergen exposure). Offspring exposed to UFPs in utero exhibited reduced inflammatory response to HDM. Compared with filtered air (FA)-exposed/HDM-challenged mice, UFP-exposed offspring had lower white blood cell counts in bronchoalveolar lavage fluid and less pronounced peribronchiolar inflammation in both strains, albeit more apparent in C57BL/6 mice. In the C57BL/6 strain, offspring exposed in utero to FA and challenged with HDM exhibited a robust response in inflammatory cytokines IL-13 and Il-17. In contrast, this response was lost in offspring exposed in utero to UFPs. Circulating IL-10 was significantly up-regulated in C57BL/6 offspring exposed to UFPs, suggesting increased regulatory T cell expression and suppressed Th2/Th17 response. Our results reveal that in utero UFP exposure at a level close to the WHO recommended PM guideline suppresses an early immune response to HDM allergen, likely predisposing neonates to respiratory infection and altering long-term pulmonary health.
Background Particulate matter (PM), a major component of ambient air pollution, accounts for a substantial burden of diseases and fatality worldwide. Maternal exposure to PM during pregnancy is particularly harmful to children’s health since this is a phase of rapid human growth and development. Method In this review, we synthesize the scientific evidence on adverse health outcomes in children following prenatal exposure to the smallest toxic components, fine (PM2.5) and ultrafine (PM0.1) PM. We highlight the established and emerging findings from epidemiologic studies and experimental models. Results Maternal exposure to fine and ultrafine PM directly and indirectly yields numerous adverse birth outcomes and impacts on children’s respiratory systems, immune status, brain development, and cardiometabolic health. The biological mechanisms underlying adverse effects include direct placental translocation of ultrafine particles, placental and systemic maternal oxidative stress and inflammation elicited by both fine and ultrafine PM, epigenetic changes, and potential endocrine effects that influence long-term health. Conclusion Policies to reduce maternal exposure and health consequences in children should be a high priority. PM2.5 levels are regulated, yet it is recognized that minority and low socioeconomic status groups experience disproportionate exposures. Moreover, PM0.1 levels are not routinely measured or currently regulated. Consequently, preventive strategies that inform neighborhood/regional planning and clinical/nutritional recommendations are needed to mitigate maternal exposure and ultimately protect children’s health.
Particulate matter (PM) causes adverse developmental outcomes following prenatal exposure, but the underlying biological mechanisms remain uncertain. Here we elucidate the effects of diesel exhaust ultrafine particle (UFP) exposure during pregnancy on placental and fetal development. Time-mated C57Bl/6n mice were gestationally exposed to UFPs at a low dose (LD, 100 µg/m3) or high dose (HD, 500 µg/m3) for 6 hours daily. Phenotypic effects on fetuses and placental morphology at gestational day (GD) of 18.5 were evaluated, and RNA sequencing was characterized for transcriptomic changes in placental tissue from male and female offspring. A significant decrease in average placental weights and crown to rump lengths was observed in female offspring in the LD exposure group. Gestational UFP exposure altered placental morphology in a dose and sex-specific manner. Average female decidua areas were significantly greater in the LD and HD groups. Maternal lacunae mean areas were increased in the female LD group, whereas fetal blood vessel mean areas were significantly greater in the male LD and HD groups. RNA sequencing indicated several disturbed cellular functions related to lipid metabolism, which were most pronounced in the LD group and especially in female placental tissue. Our findings demonstrate the vulnerability of offspring exposed to UFPs during pregnancy, highlighting sex-specific effects and emphasizing the importance of mitigating PM exposure to prevent adverse health outcomes.
Numerous studies have provided evidence that intricate interactions exist among foetoplacental, ovarian and adrenal functions during pregnancy in rats (see Petropoulos, 1973). Such interactions are shown by: maternal adrenal hypertrophy and hyperfunction in pregnancy; longer survival of gravid than non-gravid rats after adrenalectomy; placental metabolic disturbances (Petropoulos, 1973), foetal adrenal hypertrophy, and decreased litter size and neonatal body weight after maternal adrenalectomy; premature placental ageing and foetal resorption after corticosterone administration to normal pregnant rats, but full-term, successful pregnancies in protein-deprived gravid rats given corticosterone. A question as yet unanswered, however, is whether the placenta secretes corticosterone into the general corticosterone pool of the gravid rat; this question led us to consider plasma corticosterone profiles of normal pregnancy, as well as the role of ovarian, adrenal and placental function in shaping these profiles. To accomplish these ends we used the scheme of classical endocrinological experiment, following the design of a previous study (Petropoulos, 1973) with respect to animals, surgical procedures and factorial statistical analysis.Pregnant Long-Evans rats were subjected on day 13 of gestation to ovariectomy (0), adrenalectomy (A), and removal of the foetuses (F), separately and in all pos¬ sible combinations, forming the pattern of a 23 factorial design ; in all cases placentae were left in situ ; a group of pregnant intact animals was also included as a control ; five to six animals were included in each group and for each day of pregnancy studied (Table 1). Two groups of non-pregnant animals were also used: (a) ten control rats (NC) each bled on the day of dioestrus, as determined by vaginal smears ; (b) eight ovariectomized and adrenalectomized rats (NOA) bled 2-8 days after opera¬ tion, and their corticosterone values pooled in one group for statistical processing. Animal handling during blood sampling, and anaesthetic procedures were uniform for all animals. Blood was collected in heparinized plastic syringes by heart puncture under ether anaesthesia ; plasma was separated and stored frozen in glass vials for subsequent corticosterone determinations (see Lau & Timiras, 1972).In contrast with the findings reported by Kamoun (1970), plasma corticosterone levels in our control pregnant rats did not show a progressive increase during preg-
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