Effect of long-term maternal smoking on the offspring’s lung health

Saad

Machaalani

et al. 2017

Front. Mol. Neurosci.

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Hypoxic-ischemic (HI) encephalopathy occurs in approximately 6 per 1000 term newborns leading to devastating neurological consequences, such as cerebral palsy and seizures. Maternal smoking is one of the prominent risk factors contributing to HI injury. Mitochondrial integrity plays a critical role in neural injury and repair during HI. We previously showed that maternal cigarette smoke exposure (SE) can reduce brain mitochondrial fission and autophagosome markers in male offspring. This was accompanied by increased brain cell apoptosis (active caspase-3) and DNA fragmentation (TUNEL staining). Here, we aimed to investigate whether maternal SE leads to more severe neurological damage after HI brain injury in male offspring. Female BALB/c mice (8 weeks) were exposed to cigarette smoke prior to mating, during gestation, and lactation. At postnatal day 10, half of the pups from each litter underwent left carotid artery occlusion, followed by exposure to 8% oxygen (92% nitrogen). At postnatal day 40–44, maternal SE reduced grip strength in grip traction and foot fault tests, which were also reduced by HI injury to similar levels regardless of the maternal group. Limb coordination was impaired by maternal SE which was not worsened by HI injury. Maternal SE increased anxiety level in the offspring, which was normalized by HI injury. Apoptosis markers were increased in different brain regions by maternal SE, with the cortex having further increased TUNEL by HI injury, along with increased markers of inflammation and mitophagy. We conclude that maternal SE can worsen HI-induced cellular damage in male offspring well into adolescence.

Section: Discussionmentioning

confidence: 57%

Maternal Cigarette Smoke Exposure Worsens Neurological Outcomes in Adolescent Offspring with Hypoxic-Ischemic Injury

Saad

Machaalani

et al. 2017

Front. Mol. Neurosci.

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“…Our previous studies in mice have repeatedly shown that MSE can reduce the level of endogenous antioxidant Manganese Superoxide Dismutase in the brain, kidney, and lungs of adult offspring accompanied by increased Reactive Oxygen Species (ROS) levels in those organs; interestingly, antioxidant supplementation during pregnancy could completely or partially reverse the adverse effects on those organs induced by MSE (Chan et al, 2017;Sukjamnong et al, 2017Sukjamnong et al, , 2018. The endogenous antioxidant enzyme system is established in the second and third trimester of pregnancy and continues to develop in early childhood (Fanucchi, 2004).…”

Section: The Role Of Oxidative Stress In the Development Of Asthma Inmentioning

confidence: 99%

Why Do Intrauterine Exposure to Air Pollution and Cigarette Smoke Increase the Risk of Asthma?

Wang

Chen

et al. 2020

Front. Cell Dev. Biol.

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The prevalence of childhood asthma is increasing worldwide and increased in utero exposure to environmental toxicants may play a major role. As current asthma treatments are not curative, understanding the mechanisms underlying the etiology of asthma will allow better preventative strategies to be developed. This review focuses on the current understanding of how in utero exposure to environmental factors increases the risk of developing asthma in children. Epidemiological studies show that maternal smoking and particulate matter exposure during pregnancy are prominent risk factors for the development of childhood asthma. We discuss the changes in the developing fetus due to reduced oxygen and nutrient delivery affected by intrauterine environmental change. This leads to fetal underdevelopment and abnormal lung structure. Concurrently an altered immune response and aberrant epithelial and mesenchymal cellular function occur possibly due to epigenetic reprograming. The sequelae of these early life events are airway remodeling, airway hyperresponsiveness, and inflammation, the hallmark features of asthma. In summary, exposure to inhaled oxidants such as cigarette smoking or particulate matter increases the risk of childhood asthma and involves multiple mechanisms including impaired fetal lung development (structural changes), endocrine disorders, abnormal immune responses, and epigenetic modifications. These make it challenging to reduce the risk of asthma, but knowledge of the mechanisms can still help to develop personalized medicines.

“…In this instance, perhaps only epigenetic modification can explain such prolonged impairment in brain antioxidant capacity long after the maternal source of oxidants are removed . This may also explain why short‐term antioxidant supplement in the mothers during pregnancy and lactation can have such long‐lasting effect to boost endogenous antioxidant capacity in the offspring . Breastfeeding has been shown to protect the child from various metabolic conditions partially due to antioxidants in the breastmilk.…”

Section: Potential Cellular Mechanismsmentioning

confidence: 99%

“…75 This may also explain why short-term antioxidant supplement in the mothers during pregnancy and lactation can have such long-lasting effect to boost endogenous antioxidant capacity in the offspring. 4,[76][77][78] Breastfeeding has been shown to protect the child from various metabolic conditions partially due to antioxidants in the breastmilk. However, its protection of smokers' offspring seems to be limited.…”

Section: Oxidative Stress In the Brainmentioning

confidence: 99%

What lessons have we learnt about the impact of maternal cigarette smoking from animal models?

Oliver

Chen

2019

Clin Exp Pharma Physio

Self Cite

Maternal first‐ or second‐hand tobacco smoking during pregnancy is still common albeit that the detrimental effects to the unborn child are well known. Maternal tobacco cigarette smoking can affect multiple organ systems in the offspring, rendering them at increased risk of various conditions throughout life (eg. intrauterine underdevelopment, asthma, substance abuse, diabetes). However, this review will only focus on its impact on the brain and the related molecular changes in the offspring based on evidence from animal studies. Although epidemiological studies have identified the associations between maternal cigarette smoke exposure (SE) and brain disorders, animal models can help identify the underlying mechanisms and test interventions. Human studies have found that maternal SE is closely linked to small brain size and changes in brain structure and associated with a high risk of cognitive defects. Animal models suggest that this may be due to increased brain oxidative stress and inflammation during the neonatal period, leading to increased brain cell apoptosis in adulthood. There is a distinct gender bias of such impacts, where male offspring are more affected than females. Female offspring seem to have developed the adaptation by increasing endogenous antioxidant levels. Indeed, animal studies have shown that using antioxidant supplementation during pregnancy can improve neurological outcomes in male offspring, however, the efficacy in humans is yet to be confirmed. Furthermore, some animal studies suggested nicotine as the key player in intrauterine underdevelopment due to maternal SE, while human clinical trials using nicotine replacement therapy do not support this mechanism. This review will discuss the possible reasons.