BAPS Prize—1999: Lung growth induced by prenatal tracheal occlusion and its modifying factors: A study in the rat model of congenital diaphragmatic hernia

Kitano, Yoshihiro; Kanai, Masaki; Davies, Paul; Allmen, Daniel von; Yang, Eunjin; Radu, Antoneta; Kitano, Yukie; Adzick, N. Scott; Flake, Alan W.

doi:10.1053/jpsu.2001.20683

Cited by 50 publications

(52 citation statements)

References 35 publications

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“…In 1996, Keramidaris and associates (24) showed a clear relationship between the TO-induced growth response and gestational age in fetal sheep lung, with older fetuses showing a greater response. Other studies have confirmed this observation in fetal sheep (29), rabbits (10), and rats (25). There is also evidence, from studies in fetal rabbits (10) and sheep (11), that the type II cell population may be spared some of the adverse effects of TO when it is performed late in gestation for a short duration.…”

mentioning

confidence: 72%

“…As for the differences in gestational age between the two studies, there are data indicating that the ability of the fetal rodent lung to respond to TO is dependent on gestational age. Kitano and associates (25) recently reported that TO in fetal rats at 20 days of gestation for a 1.5-day period resulted in greater increases in wet and dry lung weights than TO at 18.5 days for the same duration. In that study, they did not report data for lung DNA and protein.…”

Section: Discussionmentioning

confidence: 98%

“…In studies in fetal sheep (2) and in fetal rats with diaphragmatic hernia (25), TO resulted in increased relative size and volume of potential air spaces. In contrast, Kitano and associates (26), who performed TO by tracheal ligation in normal fetal rats, reported no qualitative morphological differences when lungs from control and TO fetuses were fixed in inflation.…”

Section: Discussionmentioning

confidence: 99%

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Tracheal occlusion stimulates cell cycle progression and type I cell differentiation in lungs of fetal rats

Yoshizawa

Chapin

Sbragia

et al. 2003

American Journal of Physiology-Lung Cellular and Molecular Phys

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. Tracheal occlusion stimulates cell cycle progression and type I cell differentiation in lungs of fetal rats. Am J Physiol Lung Cell Mol Physiol 285: L344-L353, 2003. First published April 4, 2003 10.1152/ajplung.00281.2002 has been reported to stimulate lung growth but decreases number and maturation of type II cells, effects that vary with gestational age and duration of TO. We examined effects of a novel method of TO (unipolar microcautery to seal the trachea) produced at 19.5-20 days (d) of gestation in fetal rats; fetuses were delivered at term, 22 d. Controls were sham operated and unoperated littermates. TO increased wet lung weight but not dry lung weight or lung DNA and protein. To evaluate further the effects of TO, we examined the cell cycle regulators, cyclins D1 and A, in fetal lungs. Cyclin D1 increased with TO (P Ͻ 0.005). TO also increased expression of the type I epithelial cell marker RTI40 (mRNA and protein). TO decreased mRNA for surfactant proteins (SP)-A and -C but did not affect protein levels of SP-A and -B and of RTII70, a type II epithelial cell marker. We conclude that TO by microcautery, even of short duration, has diverse pulmonary effects including stimulating increased levels of cyclin D1 with probable cell cycle progression, type I cell differentiation, and possibly inhibiting type II cell function.cyclins; fetal lung development; lung growth; pulmonary epithelial differentiation; pulmonary surfactant LATE IN GESTATION, the fetal lung rapidly changes in appearance from an almost glandular tissue into a lacy, thin-walled organ capable of efficient gas exchange and surfactant production. During this period lung growth, septal thinning, maturation of the surfactant system, and differentiation of alveolar type I and type II cells occur. Normal fetal lung development is crucial for survival in extrauterine life, but factors that control these developmental processes and their interdependence have been incompletely defined.Lung growth and maturation of the surfactant system are the most widely studied aspects of late fetal lung development. Fetal lung growth is dependent on several mechanical factors, including adequate intrathoracic space, sufficient amniotic fluid volume, normal fetal breathing movements, and a positive transpulmonary distending pressure (21,27). In contrast, maturation of the surfactant system is highly dependent on endocrine factors (4, 50). There is relatively little information about factors that are responsible for differentiation of alveolar epithelial type I and type II cells in vivo.Several investigators have shown that occlusion of the trachea in experimental animals increases lung growth but has adverse affects on type II cell number and function (2,10,11,15,40). These changes occur when tracheal occlusion (TO) is produced relatively early in gestation and maintained for a prolonged period. In contrast, when TO is produced later in gestation for a relatively short period, lung growth is stimulated, and adverse affects on the type II cell population are di...

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mentioning

confidence: 72%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

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Tracheal occlusion stimulates cell cycle progression and type I cell differentiation in lungs of fetal rats

Yoshizawa

Chapin

Sbragia

et al. 2003

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Resultados promissores de intervenção fetal para HDC com a colocação transitória de um balão intra-traqueal percutâneo, ocorrem quando associadas às medidas pulmonares e a posição hepática 12 . O efeito maturador da TO parece residir, sobretudo, na ação mecânica que exerce no parênquima pulmonar, consoante ao demonstrado que a aceleração do crescimento celular está diretamente relacionada ao aumento da pressão intratraqueal 13,14,15 . Esse estímulo físico, além de recuperar o espaço pulmonar perdido pela herniação na HDC e restabelecer a arquitetura pulmonar, estimula processos moleculares, culminando com maior transcrição gênica, maior produção protéica e conseqüentemente desenvolvimento e diferenciação celular confluindo para acelerar a maturação pulmonar 7,16 .…”

Section: Discussionunclassified

Traqueo-oclusão intra-útero: técnica cirúrgica associada à corticoterapia promove aumento nos receptores de VEGF (Vascular Endothelial Growth Factor) em pulmões de fetos de ratas

Iscaife

Gonçalves

Silveira

et al. 2007

Rev. Med. (São Paulo)

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Introdução: A hérnia diafragmática congênita (HDC) causa hipoplasia e hipertensão pulmonar e em geral leva a alta morbidade e mortalidade neonatal. Traqueo-oclusão fetal (TO) e corticoterapia pré-natal são alternativas para acelerar o crescimento pulmonar fetal e diminuir a hipoplasia na HDC. A produção de VEGF (Vascular Endothelial Growth Factor) está relacionada com a maturidade pulmonar e sofre alterações na HDC ainda não elucidadas. Materiais e métodos: Seis grupos de 12 fetos de ratos Spreague-Dawley foram comparados: TO, Sham, Controle, TO+Dex, Sham+Dex e Controle+Dex. No dia 18,5º foi realizada TO com e sem corticoterapia utilizando dexametasona. No 21,5º dia gestacional os pesos corporal e pulmonar foram mensurados. Realizou-se imunohistoquímica para VEGFR-1 (Flt-1), VEGFR-2 (Flk-1), seguida de morfometria. Resultados: O VEGFR-1 estava aumentado no TO (p<0.05)e na TO+Dex (p<0.05). O VEGFR-2 teve aumento significativo quando comparamos TO e TO+Dex com o controle (p<0,05). Conclusão: A TO associada ao uso de corticoesteróide aumentou o número de VEGFR-1 e VEGFR-2 em pulmões de fetos de ratas.

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“…O Nitrofen é um terató-geno que quando administrado no dia gestacional (DG) 9,5, na dose de 100 mg, causa HDC em cerca de 40% dos fetos de ratas 27 . O modelo de HDC em ratos tem várias vantagens: curto período gestacional (termo corresponde ao 22º dia de gestação), maior número de fetos por gestação, baixo custo de aquisição e manutenção, além de possibilitar uma vasta gama de estudos de biologia molecular, não disponíveis em animais de maior porte 28 .…”

Section: Modelos Animais Para Estudar Hérnia Diafragmática Congênitaunclassified

Manejo pré-natal da hérnia diafragmática congênita: presente, passado e futuro

Gallindo

Gonçalves

Figueira

et al. 2015

Rev. Bras. Ginecol. Obstet.

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Manejo pré-natal da hérnia diafragmática congênita: presente, passado e futuro ResumoA hérnia diafragmática congênita é um defeito de formação do diafragma que acomete entre 1:2.000 e 1:4.000 nascidos vivos e constitui 8% das principais anomalias congênitas. Avanços médicos nos últimos 30 anos envolvendo diagnóstico pré-natal, intervenção fetal, manejo clinico e cirúrgico neonatal têm mudado a sobrevivência dos seus portadores. A evolução histórica desses avanços ajuda a compreender o esforço na busca de melhores resultados desse defeito muitas vezes fatal. Perspectivas na utilização de bioengenharia e terapia envolvendo células tronco podem trazer novas esperanças para os fetos com hérnia diafragmática congênita. AbstractThe congenital diaphragmatic hernia is a defect in the formation of the diaphragm, which affects between 1:2,000 and 1:4,000 live births and represents 8% of major congenital anomalies. Medical advances in the last 30 years involving prenatal diagnosis, fetal intervention, neonatal surgical and clinical management have changed the survival of these patients. The historical evolution of these advances helps us to understand the effort in pursuit of better results of this defect, which is often lethal. Perspectives on the use of bioengineering and therapy involving stem cells may bring new hope for fetuses with congenital diaphragmatic hernia.

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BAPS Prize—1999: Lung growth induced by prenatal tracheal occlusion and its modifying factors: A study in the rat model of congenital diaphragmatic hernia

Cited by 50 publications

References 35 publications

Tracheal occlusion stimulates cell cycle progression and type I cell differentiation in lungs of fetal rats

Tracheal occlusion stimulates cell cycle progression and type I cell differentiation in lungs of fetal rats

Traqueo-oclusão intra-útero: técnica cirúrgica associada à corticoterapia promove aumento nos receptores de VEGF (Vascular Endothelial Growth Factor) em pulmões de fetos de ratas

Manejo pré-natal da hérnia diafragmática congênita: presente, passado e futuro

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