BACKGROUND: Fetal growth restriction (FGR) is a major risk factor for bronchopulmonary dysplasia (BPD). Maternal stress and poor diet are linked to FGR. Effect of perinatal stress on lung development remains unknown. OBJECTIVE: Using a murine model of adverse early life environment (AELE), we hypothesized that maternal exposure to perinatal environmental stress and high-fat diet (Western diet) lead to impaired lung development in the offspring. METHODS: Female mice were placed on either control diet or Western diet before conception. Those exposed to Western diet were also exposed to perinatal environmental stress, the combination referred to as AELE. Pups were either euthanized at postnatal day 21 (P21) or weaned to control diet and environment until adulthood (8-14 wk old). Lungs were harvested for histology, gene expression by quantitative RT-PCR, microRNA profiling, and immunoblotting. RESULTS: AELE increased the mean linear intercept and decreased the radial alveolar count and secondary septation in P21 and adult mice. Capillary count was also decreased in P21 and adult mice. AELE lungs had decreased vascular endothelial growth factor A (VEGFA), VEGF receptor 2, endothelial nitric oxide synthase, and hypoxia inducible factor-1α protein levels and increased expression of genes that regulate DNA methylation and upregulation of microRNAs that target genes involved in lung development at P21. CONCLUSION: AELE leads to impaired lung alveolar and vascular growth, which persists into adult age despite normalizing the diet and environment at P21. AELE also alters the expression of genes involved in lung remodeling.
BACKGROUND: Fetal growth restriction (FGR) is a major risk factor for bronchopulmonary dysplasia (BPD). Maternal stress and poor diet are linked to FGR. Effect of perinatal stress on lung development remains unknown. OBJECTIVE: Using a murine model of adverse early life environment (AELE), we hypothesized that maternal exposure to perinatal environmental stress and high-fat diet (Western diet) lead to impaired lung development in the offspring. METHODS: Female mice were placed on either control diet or Western diet before conception. Those exposed to Western diet were also exposed to perinatal environmental stress, the combination referred to as AELE. Pups were either euthanized at postnatal day 21 (P21) or weaned to control diet and environment until adulthood (8-14 wk old). Lungs were harvested for histology, gene expression by quantitative RT-PCR, microRNA profiling, and immunoblotting. RESULTS: AELE increased the mean linear intercept and decreased the radial alveolar count and secondary septation in P21 and adult mice. Capillary count was also decreased in P21 and adult mice. AELE lungs had decreased vascular endothelial growth factor A (VEGFA), VEGF receptor 2, endothelial nitric oxide synthase, and hypoxia inducible factor-1α protein levels and increased expression of genes that regulate DNA methylation and upregulation of microRNAs that target genes involved in lung development at P21. CONCLUSION: AELE leads to impaired lung alveolar and vascular growth, which persists into adult age despite normalizing the diet and environment at P21. AELE also alters the expression of genes involved in lung remodeling.
Authors: Barbara J Stoll; Nellie I Hansen; Edward F Bell; Seetha Shankaran; Abbot R Laptook; Michele C Walsh; Ellen C Hale; Nancy S Newman; Kurt Schibler; Waldemar A Carlo; Kathleen A Kennedy; Brenda B Poindexter; Neil N Finer; Richard A Ehrenkranz; Shahnaz Duara; Pablo J Sánchez; T Michael O'Shea; Ronald N Goldberg; Krisa P Van Meurs; Roger G Faix; Dale L Phelps; Ivan D Frantz; Kristi L Watterberg; Shampa Saha; Abhik Das; Rosemary D Higgins Journal: Pediatrics Date: 2010-08-23 Impact factor: 7.124
Authors: Carl Bose; Linda J Van Marter; Matthew Laughon; T Michael O'Shea; Elizabeth N Allred; Padmani Karna; Richard A Ehrenkranz; Kim Boggess; Alan Leviton Journal: Pediatrics Date: 2009-08-17 Impact factor: 7.124
Authors: Sofia Nascimento Dos Santos; Helen Sheldon; Jonathas Xavier Pereira; Christopher Paluch; Esther M Bridges; Márcia Curry El-Cheikh; Adrian L Harris; Emerson Soares Bernardes Journal: Oncotarget Date: 2017-07-25
Authors: Nia McRae; Chris Gennings; Nadya Rivera Rivera; Marcela Tamayo-Ortiz; Ivan Pantic; Chitra Amarasiriwardena; Lourdes Schnaas; Rosalind Wright; Martha M Tellez-Rojo; Robert O Wright; Maria José Rosa Journal: Environ Res Date: 2021-11-27 Impact factor: 6.498