Prenatal and postnatal mothering by diesel exhaust PM2.5-exposed dams differentially program mouse energy metabolism

Abstract

BackgroundObesity is one of the leading threats to global public health. It is consequent to abnormal energy metabolism. Currently, it has been well established that maternal exposure to environmental stressors that cause inappropriate fetal development may have long-term adverse effects on offspring energy metabolism in an exposure timing-dependent manner, known as developmental programming of health and diseases paradigm. Rapidly increasing evidence has indicated that maternal exposure to ambient fine particles (PM2.5) correlates to abnormal fetal development. In the present study, we therefore assessed whether maternal exposure to diesel exhaust PM2.5 (DEP), the major component of ambient PM2.5 in urban areas, programs offspring energy metabolism, and further examined how the timing of exposure impacts this programming.ResultsThe growth trajectory of offspring shows that although prenatal maternal exposure to DEP did not impact the birth weight of offspring, it significantly decreased offspring body weight from postnatal week 2 until the end of observation. This weight loss effect of prenatal maternal exposure to DEP coincided with decreased food intake but not alteration in brown adipose tissue (BAT) morphology. The hypophagic effect of prenatal maternal exposure to DEP was in concord with decreased hypothalamic expression of an orexigenic peptide NPY, suggesting that the prenatal maternal exposure to DEP impacts offspring energy balance primarily through programming of food intake. Paradoxically, the reduced body weight resulted from prenatal maternal exposure to DEP was accompanied by increased mass of epididymal adipose tissue, which was due to hyperplasia as morphological analysis did not observe any hypertrophy. In direct contrast, the postnatal mothering by DEP-exposed dams increased offspring body weight during lactation and adulthood, paralleled by markedly increased fat accumulation and decreased UCP1 expression in BAT but not alteration in food intake. The weight gain induced by postnatal mothering by DEP-exposed dams was also expressed as an increased adiposity. But it concurred with a marked hypertrophy of adipocytes.ConclusionPrenatal and postnatal mothering by DEP-exposed dams differentially program offspring energy metabolism, underscoring consideration of the exposure timing when examining the adverse effects of maternal exposure to ambient PM2.5.

Prenatal exposure to diesel exhaust PM2.5 causes offspring β cell dysfunction in adulthood

“…Therefore, as per the DPoHaD paradigm, maternal exposure to ambient PM 2.5 is likely to be a risk factor for the DPoHaD. In agreement with this, we recently demonstrated that maternal exposure to diesel exhaust PM 2.5 (DEP, one of the major sources of ambient PM 2.5 in urban areas) persistently influences male offspring's development and increases their adulthood adiposity (6). As obesity is one of the major risk factors for diabetes, how maternal exposure to DEP influences offspring's glucose homeostasis has to be determined.…”

“…Prenatal exposure to DEP results in glucose intolerance in adult male offspring. We recently reported that dams' prenatal or postnatal exposure to DEP differentially programs mouse E74 PM2.5 EXPOSURE AND OFFSPRING ␤ CELL FUNCTION energy metabolism and adiposity in adulthood (6). As adiposity is well known to correlate to glucose homeostasis, we performed glucose homeostasis assessments on these adult male offspring.…”

“…We recently showed that dams' prenatal or postnatal exposure to DEP differentially impacts the growth trajectory of offspring (6). In the present study, we systemically examined their long-term effects on offspring's glucose homeostasis.…”

Concentrated Ambient PM2.5-Induced Inflammation and Endothelial Dysfunction in a Murine Model of Neural IKK2 Deficiency

“…Following amplification, a dissociation curve analysis was performed to ensure purity of PCR product. The specific sense and antisense primers for tumor necrosis factor- , interleukin (IL)-6, , and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) (the reference housekeeping gene) were previously described ( Chen et al. 2017 ).…”

Impact of exposure to diesel exhaust during pregnancy on mammary gland development and milk composition in the rabbit

“…An increasing number of studies in both human and animal models have shown that prenatal exposure to ambient fine particles is associated with a variety of abnormalities during foetal development, such as preterm birth, low birth weight and placental dysfunctions [14–17]. Moreover, there is clear evidence that gestational exposure to pollutants can also have deleterious long term effects that mainly involve energy metabolism disorders [18, 19] and cardiac and respiratory dysfunctions [4, 20, 21]. We have previously reported that females exposed daily during pregnancy to DE particles at levels close to urban pollution evidenced foeto-placental disorders [14].…”