NRF2-Dependent Placental Effects Vary by Sex and Dose following Gestational Exposure to Ultrafine Particles

Behlen, Jonathan; Lau, Carmen; Pendleton, Drew; Li, Yixin; Hoffmann, Aline Rodrigues; Golding, Michael C.; Zhang, Renyi; Johnson, Natalie M.

doi:10.3390/antiox11020352

Cited by 2 publications

(3 citation statements)

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“…PM exposure was carried out as previously described in Behlen et al and Lau et al [ 12 , 27 , 53 ]. Mice ( n = 18 for FA; n = 18 for UFPs) were exposed from GD0.5 to 13.5 for 6 h/day in whole-body inhalation chambers.…”

Section: Methodsmentioning

confidence: 99%

“…The UFP chamber was monitored, and the flow of HEPA-filtered air adjusted accordingly to maintain particle concentrations of ~ 100 g /m 3 throughout the study. This dose was based on previously observed effects on offspring health [ 12 , 27 , 53 ]. Moreover, this dose was equivalent to a 24-h average exposure 25 g /m 3 , just under the EPA PM 2.5 regulatory level (35 g /m 3 ).…”

Section: Methodsmentioning

confidence: 99%

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Maternal exposure to ultrafine particles enhances influenza infection during pregnancy

et al. 2023

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Background Interactions between air pollution and infectious agents are increasingly recognized and critical to identify, especially to protect vulnerable populations. Pregnancy represents a vulnerable period for influenza infection and air pollution exposure, yet interactions during pregnancy remain unclear. Maternal exposure to ultrafine particles (UFPs, $$\le$$ ≤ 100 nm diameter), a class of particulate matter ubiquitous in urban environments, elicits unique pulmonary immune responses. We hypothesized that UFP exposure during pregnancy would lead to aberrant immune responses to influenza enhancing infection severity. Results Building from our well-characterized C57Bl/6N mouse model employing daily gestational UFP exposure from gestational day (GD) 0.5–13.5, we carried out a pilot study wherein pregnant dams were subsequently infected with Influenza A/Puerto Rico/8/1934 (PR8) on GD14.5. Findings indicate that PR8 infection caused decreased weight gain in filtered air (FA) and UFP-exposed groups. Co-exposure to UFPs and viral infection led to pronounced elevation in PR8 viral titer and reduced pulmonary inflammation, signifying potential suppression of innate and adaptive immune defenses. Pulmonary expression of the pro-viral factor sphingosine kinase 1 (Sphk1) and pro-inflammatory cytokine interleukin-1β (IL-1$$\beta$$ β ) was significantly increased in pregnant mice exposed to UFPs and infected with PR8; expression correlated with higher viral titer. Conclusions Results from our model provide initial insight into how maternal UFP exposure during pregnancy enhances respiratory viral infection risk. This model is an important first step in establishing future regulatory and clinical strategies for protecting pregnant women exposed to UFPs.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Maternal exposure to ultrafine particles enhances influenza infection during pregnancy

et al. 2023

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“…For example, the placental malfunction associated abnormal intrauterine environment during the embryonic period not only inhibits the fetus’ development and growth but also increases the risk of diabetes, hypertension and cardiovascular diseases after birth [ 2 ]. Even though multiple risk factors are attributed to placental dysfunctions, one of them is oxidative stress [ 3 , 4 ]. It has been reported that maternal exposure to high levels of reactive oxygen species (ROS) during pregnancy impairs placental function and leads to poor outcomes in pregnancy [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Melatonin Supplementation during the Late Gestational Stage Enhances Reproductive Performance of Sows by Regulating Fluid Shear Stress and Improving Placental Antioxidant Capacity

et al. 2023

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In this study, the effects of daily melatonin supplementation (2 mg/kg) at the late gestational stage on the reproductive performance of the sows have been investigated. This treatment potentially increased the litter size and birth survival rate and significantly increased the birth weight as well as the weaning weight and survival rate of piglets compared to the controls. The mechanistic studies have found that these beneficial effects of melatonin are not mediated by the alterations of reproductive hormones of estrogen and progesterone, nor did the glucose and lipid metabolisms, but they were the results of the reduced oxidative stress in placenta associated with melatonin supplementation. Indeed, the melatonergic system, including mRNAs and proteins of AANAT, MTNR1A and MTNR1B, has been identified in the placenta of the sows. The RNA sequencing of placental tissue and KEGG analysis showed that melatonin activated the placental tissue fluid shear stress pathway to stimulate the Nrf2 signaling pathway, which upregulated its several downstream antioxidant genes, including MGST1, GSTM3 and GSTA4, therefore, suppressing the placental oxidative stress. All these actions may be mediated by the melatonin receptor of MTNR1B.

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NRF2-Dependent Placental Effects Vary by Sex and Dose following Gestational Exposure to Ultrafine Particles

Cited by 2 publications

References 50 publications

Maternal exposure to ultrafine particles enhances influenza infection during pregnancy

Maternal exposure to ultrafine particles enhances influenza infection during pregnancy

Melatonin Supplementation during the Late Gestational Stage Enhances Reproductive Performance of Sows by Regulating Fluid Shear Stress and Improving Placental Antioxidant Capacity

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