Pre‐ and Postnatal Lung Development: An Updated Species Comparison

Lewin, Geertje; Hurtt, Mark E.

doi:10.1002/bdr2.1089

Cited by 20 publications

(16 citation statements)

References 108 publications

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“…The pathogenesis of the characteristic arrest of the acinar development and interstitial thickening with mesenchymal cells has not been closely studied. In the stillborn affected puppy, the acinar structure was in the saccular stage of development, which is normal for at term puppies [20] and interstitial thickening was not apparent at this stage, whereas the aforementioned abnormalities were clearly seen in the older affected puppies. This suggests that the acinar and interstitial changes manifest and progress during breathing and that these changes could be secondary and reflect a reparative mechanism to the injured alveolar septa and atelectasis.…”

Section: Plos Geneticsmentioning

confidence: 92%

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Recessive missense LAMP3 variant associated with defect in lamellar body biogenesis and fatal neonatal interstitial lung disease in dogs

et al. 2020

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Neonatal interstitial lung diseases due to abnormal surfactant biogenesis are rare in humans and have never been reported as a spontaneous disorder in animals. We describe here a novel lung disorder in Airedale Terrier (AT) dogs with clinical symptoms and pathology similar to the most severe neonatal forms of human surfactant deficiency. Lethal hypoxic respiratory distress and failure occurred within the first days or weeks of life in the affected puppies. Transmission electron microscopy of the affected lungs revealed maturation arrest in the formation of lamellar bodies (LBs) in the alveolar epithelial type II (AECII) cells. The secretory organelles were small and contained fewer lamellae, often in combination with small vesicles surrounded by an occasionally disrupted common limiting membrane. A combined approach of genome-wide association study and whole exome sequencing identified a recessive variant, c.1159G>A, p.(E387K), in LAMP3, a limiting membrane protein of the cytoplasmic surfactant organelles in AECII cells. The substitution resides in the LAMP domain adjacent to a conserved disulfide bond. In summary, this study describes a novel interstitial lung disease in dogs, identifies a new candidate gene for human surfactant dysfunction and brings important insights into the essential role of LAMP3 in the process of the LB formation.

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Section: Plos Geneticsmentioning

confidence: 92%

“…The lungs of the stillborn puppy were at the normal saccular stage of maturation [20]. Some of the alveolar spaces contained strands and globules of Periodic acid Schiff (PAS) -positive eosinophilic material and macrophages.…”

Section: Respiratory Symptoms and Lung-specific Pathology In The Affementioning

confidence: 99%

Recessive missense LAMP3 variant associated with defect in lamellar body biogenesis and fatal neonatal interstitial lung disease in dogs

et al. 2020

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“…As early as 30-60 days gestation, innate and adaptive immune cells have been found in umbilical cord and lymphoid organs (185)(186)(187)(188)(189)(190). Additionally, the preterm piglets at ∼97-106 gestational days (191,192) closely reflects the saccular phase of humans (∼24-38 weeks) (160,193). However, despite these strengths, very few studies of chorioamnionitis have been conducted in this model.…”

Section: Pigmentioning

confidence: 99%

“…The timeline of lung development is more similar between rodents and humans, but differences do exist. The majority of lung development occurs in utero for both species with the canalicular-saccular phase in mice (∼17days-birth) reflecting changes occurring during the 15-38 weeks of gestation in humans (159,160). However, alveolarization begins during late gestation in humans (36 weeks) and only postnatally in the mouse (post-natal day 4) (4, 161).…”

Section: Rodentsmentioning

confidence: 99%

Pulmonary Consequences of Prenatal Inflammatory Exposures: Clinical Perspective and Review of Basic Immunological Mechanisms

et al. 2020

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Chorioamnionitis, a potentially serious inflammatory complication of pregnancy, is associated with the development of an inflammatory milieu within the amniotic fluid surrounding the developing fetus. When chorioamnionitis occurs, the fetal lung finds itself in the unique position of being constantly exposed to the consequent inflammatory meditators and/or microbial products found in the amniotic fluid. This exposure results in significant changes to the fetal lung, such as increased leukocyte infiltration, altered cytokine, and surfactant production, and diminished alveolarization. These alterations can have potentially lasting impacts on lung development and function. However, studies to date have only begun to elucidate the association between such inflammatory exposures and lifelong consequences such as lung dysfunction. In this review, we discuss the pathogenesis of and fetal immune response to chorioamnionitis, detail the consequences of chorioamnionitis exposure on the developing fetal lung, highlighting the various animal models that have contributed to our current understanding and discuss the importance of fetal exposures in regard to the development of chronic respiratory disease. Finally, we focus on the clinical, basic, and therapeutic challenges in fetal inflammatory injury to the lung, and propose next steps and future directions to improve our therapeutic understanding of this important perinatal stress.

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“…2). [6][7][8][9][10][11][12] In this review, we report the different models of CDH that have been employed over the years and we describe how discoveries using these models have been or might be translated to the treatment of CDH in humans.…”

Section: Introductionmentioning

confidence: 99%

Congenital Diaphragmatic Hernia: State of the Art in Translating Experimental Research to the Bedside

et al. 2019

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Congenital diaphragmatic hernia (CDH) is a devastating disease that still carries a high mortality and morbidity rate. Poor outcomes for fetuses and infants with CDH are mainly related to pulmonary hypoplasia (PH) and pulmonary vascular remodeling that leads to pulmonary hypertension (PHTN). Over the last five decades, research efforts have focused on modeling CDH not only to study the pathophysiology of the diaphragmatic defect, pulmonary hypoplasia, and pulmonary hypertension, but also to identify therapies that would promote lung growth and maturation, and correct vascular remodeling. As CDH is a multifactorial condition whose etiology remains unknown, there is not a single model of CDH, rather several ones that replicate different aspects of this disease. While small animals like the mouse and the rat have mainly been used to uncover biological pathways underlying the diaphragmatic defect and poor lung growth, larger animals like the lamb and the rabbit models have been instrumental for pursuing medical and surgical interventions. Overall, the use of animal models has indeed advanced our knowledge on CDH and helped us test innovative therapeutic options. For example, the lamb model of CDH has been the paradigm for testing fetal surgical procedures, including tracheal occlusion, which has been translated to clinical use. In this review, we outline the induction protocols of CDH in animals with the use of chemicals, dietary changes, genetic alterations, and surgical maneuvers, and we describe the studies that have translated experimental results to the bedside.

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Pre‐ and Postnatal Lung Development: An Updated Species Comparison

Cited by 20 publications

References 108 publications

Recessive missense LAMP3 variant associated with defect in lamellar body biogenesis and fatal neonatal interstitial lung disease in dogs

Recessive missense LAMP3 variant associated with defect in lamellar body biogenesis and fatal neonatal interstitial lung disease in dogs

Pulmonary Consequences of Prenatal Inflammatory Exposures: Clinical Perspective and Review of Basic Immunological Mechanisms

Congenital Diaphragmatic Hernia: State of the Art in Translating Experimental Research to the Bedside

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