Sex-differences in LPS-induced neonatal lung injury

Nguyen, Leanna; Castro, Odalis; Dios, Robyn De; Sandoval, Jeryl; McKenna, Sarah; Wright, Clyde J.

doi:10.1038/s41598-019-44955-0

Cited by 16 publications

(7 citation statements)

References 111 publications

(97 reference statements)

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“…We selected this time point as it is the stage of murine development consistent with a human neonate born at term. We measured mean linear intercept (MLI), an objective measurement of alveolar development that reflects the average distance between alveoli [ 44 , 45 ]. MLI was increased in Se deficient pups compared to Se sufficient pups ( Figure 2 A,B).…”

Section: Resultsmentioning

confidence: 99%

Neonatal Selenium Deficiency Decreases Selenoproteins in the Lung and Impairs Pulmonary Alveolar Development

et al. 2022

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Decreased selenium (Se) levels during childhood and infancy are associated with worse respiratory health. Se is biologically active after incorporation into Se-containing antioxidant enzymes (AOE) and proteins. It is unknown how decreased maternal Se during pregnancy and lactation impacts neonatal pulmonary selenoproteins, growth, and lung development. Using a model of neonatal Se deficiency that limits Se intake to the dam during pregnancy and lactation, we evaluated which neonatal pulmonary selenoproteins are decreased in both the saccular (postnatal day 0, P0) and early alveolar (postnatal day 7, P7) stages of lung development. We found that Se deficient (SeD) pups weigh less and exhibit impaired alveolar development compared to Se sufficient (SeS) pups at P7. The activity levels of glutathione peroxidase (GPx) and thioredoxin reductase (Txnrd) were decreased at P0 and P7 in SeD lungs compared to SeS lungs. Protein content of GPx1, GPx3 and Txnrd1 were decreased in SeD lungs at P0 and P7, whereas Txnrd2 content was unaltered compared to SeS controls. The expression of NRF-2 dependent genes and several non-Se containing AOE were similar between SeS and SeD lungs. SeD lungs exhibited a decrease in selenoprotein N, an endoplasmic reticulum protein implicated in alveolar development, at both time points. We conclude that exposure to Se deficiency during pregnancy and lactation impairs weight gain and lung growth in offspring. Our data identify multiple selenoproteins in the neonatal lung that are vulnerable to decreased Se intake, which may impact oxidative stress and cell signaling under physiologic conditions as well as after oxidative stressors.

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Section: Resultsmentioning

confidence: 99%

Neonatal Selenium Deficiency Decreases Selenoproteins in the Lung and Impairs Pulmonary Alveolar Development

et al. 2022

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“…A study of 2-day-old Wistar rats challenged with endotoxin demonstrated no significant changes in cytokine profiles (111). Similarly, in examining lung-related outcomes after intraperitoneal injection of endotoxin, no sex-dependent pulmonary injury, and no differences in NF-κB activation were demonstrated (112). Evidence does suggest, however, that innate immunity is affected by sex hormones (113).…”

Section: Sex-dependent Differences In Neonatal Sepsismentioning

confidence: 99%

Sex- and Gender-Dependent Differences in Clinical and Preclinical Sepsis

Zhang

Macala

Fox‐Robichaud

et al. 2021

Shock

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In this mini-review we provide an overview of sex-and gender-dependent issues in both clinical and preclinical sepsis. The increasing recognition for the need to account for sex and gender in biomedical research brings a unique set of challenges and requires researchers to adopt best practices when conducting and communicating sex-and gender-based research. This may be of particular importance in sepsis, given the potential contribution of sex bias in the failures of translational sepsis research in adults and neonates. Clinical evidence of sex-dependent differences in sepsis is equivocal. Since clinical studies are limited to observational data and confounded by a multitude of factors, preclinical studies provide a unique opportunity to investigate sex differences in a controlled, experimental environment. Numerous preclinical studies have suggested that females may experience favorable outcomes in comparison with males. The underlying mechanistic evidence for sex-dependent differences in sepsis and other models of shock (e.g., trauma-hemorrhage) largely centers around the beneficial effects of estrogen. Other mechanisms such as the immunosuppressive role of testosterone and Xlinked mosaicism are also thought to contribute to observed sex-and gender-dependent differences in sepsis. Significant knowledge gaps still exist in this field. Future investigations can address these gaps through careful consideration of sex and gender in clinical studies, and the use of clinically accurate preclinical models that reflect sex differences. A better understanding of sex-and gender-dependent differences may serve to increase translational research success.

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“…CCR2 signaling is required for lung pro-fibrotic responses in mice (37)(38)(39) and partially mediates hyperoxia-induced hypoalveolarization in immature mice (40). Recent studies implicate a role for repetitive LPS exposure in pulmonary hypoalveolarization and inflammation, including increased CCL2 expression (13,(41)(42)(43). However, the role of innate immune cells recruited in response to increased CCL2 expression and their pro-inflammatory signals has not been investigated.…”

Section: Introductionmentioning

confidence: 99%