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18.03.2016 | Original Article

Combined antenatal therapy with retinoic acid and tracheal occlusion in a rat model of congenital diaphragmatic hernia

verfasst von: Augusto Frederico Schmidt, Frances Lilian Lanhellas Gonçalves, Rebeca Lopes Figueira, Federico Scorletti, Jose Luis Peiró, Lourenço Sbragia

Erschienen in: Pediatric Surgery International | Ausgabe 6/2016

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Abstract

Aim

To investigate the effect of combined prenatal treatment with retinoic acid (RA) and tracheal occlusion (TO) on the pulmonary vascular morphology and expression of vascular endothelial growth factors (VEGF) and its receptors in a rat model of congenital diaphragmatic hernia (CDH).

Material and methods

Rats were given nitrofen at 9 days of gestation followed by no treatment (CDH), RA (CDH + RA), TO (CDH + TO), or both (CDH + RA + TO) (n = 16). We measured the median wall thickness of the pulmonary arterioles (MWT) and analyzed the expression of VEGF and its receptors (VEGFR1 and VEGFR2).

Results

Compared to control animals, CDH had increased MWT (44 ± 15 vs. 58 ± 7; p < 0.05) and decreased expression of VEGF, VEGFR1, and VEGFR2 (p < 0.05). Treatment with RA or TO alone, and RA + TO reduced the MWT (46 ± 9, 42 ± 11, 46 ± 8, respectively) and improved the expression of VEGF, VEGFR1, and VEGFR2 compared to CDH (p < 0.05). However, the combination of RA + TO did not confer additional benefit in the reduction of the MWT or in increasing the VEGF and its receptors compared to either treatment alone.

Conclusion

Antenatal treatment with either RA or TO improved the MWT and expression of VEGF and its receptors in a CDH rat model. However, combined treatment with RA + TO was not superior to either treatment alone.

Rollins MD (2012) Recent advances in the management of congenital diaphragmatic hernia. Curr Opin Pediatr 24:379–385. doi:10.1097/MOP.0b013e328352c4f2 CrossRefPubMed

Veenma DC, de Klein A, Tibboel D (2012) Developmental and genetic aspects of congenital diaphragmatic hernia. Pediatr Pulmonol 47:534–545. doi:10.1002/ppul.22553 CrossRefPubMed

van den Hout L, Schaible T, Cohen-Overbeek TE et al (2011) Actual outcome in infants with congenital diaphragmatic hernia: the role of a standardized postnatal treatment protocol. Fetal Diagn Ther 29:55–63. doi:10.1159/000322694 CrossRefPubMed

Sylvester KG, Rasanen J, Kitano Y et al (1998) Tracheal occlusion reverses the high impedance to flow in the fetal pulmonary circulation and normalizes its physiological response to oxygen at full term. J Pediatr Surg 33:1071–1074 (discussion 1074–1075)

Roubliova XI, Verbeken EK, Wu J et al (2004) Effect of tracheal occlusion on peripheric pulmonary vessel muscularization in a fetal rabbit model for congenital diaphragmatic hernia. Am J Obstet Gynecol 191:830–836CrossRefPubMed

Schmidt AF, Gonçalves FL, Regis AC et al (2012) Prenatal retinoic acid improves lung vascularization and VEGF expression in CDH rat. Am J Obstet Gynecol 207:76.e26–76.e32

Saito A, Sugawara A, Uruno A et al (2007) All-trans retinoic acid induces in vitro angiogenesis via retinoic acid receptor: possible involvement of paracrine effects of endogenous vascular endothelial growth factor signaling. Endocrinology 148:1412–1423CrossRefPubMed

Wongtrakool C, Malpel S, Gorenstein J et al (2003) Down-regulation of retinoic acid receptor alpha signaling is required for sacculation and type I cell formation in the developing lung. J Biol Chem 278:46911–46918CrossRefPubMedPubMedCentral

Chazaud C, Dollé P, Rossant J et al (2003) Retinoic acid signaling regulates murine bronchial tubule formation. Mech Dev 120(6):691–700CrossRefPubMed

10.

Montedonico S, Sugimoto K, Felle P et al (2008) Prenatal treatment with retinoic acid promotes pulmonary alveologenesis in the nitrofen model of congenital diaphragmatic hernia. J Pediatr Surg 43(3):500–507. doi:10.1016/j.jpedsurg.2007.10.030 CrossRefPubMed

11.

Sugimoto K, Takayasu H, Nakazawa N et al (2008) Prenatal treatment with retinoic acid accelerates type 1 alveolar cell proliferation of the hypoplastic lung in the nitrofen model of congenital diaphragmatic hernia. J Pediatr Surg 43:367–372CrossRefPubMed

12.

Schmidt AF, Gonçalves FL, Nassr AC et al (2010) Antenatal steroid and tracheal occlusion restore vascular endothelial growth factor receptors in congenital diaphragmatic hernia rat model. Am J Obstet Gynecol 203:184.e13–184.e20. doi:10.1016/j.ajog.2010.04.022

13.

Kluth D, Kangah R, Reich P et al (1990) Nitrofen-induced diaphragmatic hernias in rats: an animal model. J Pediatr Surg 25:850–854CrossRefPubMed

14.

Shehata SM, Mooi WJ, Okazaki T et al (1999) Enhanced expression of vascular endothelial growth factor in lungs of newborn infants with congenital diaphragmatic hernia and pulmonary hypertension. Thorax 54:427–431CrossRefPubMedPubMedCentral

15.

Geggel RL, Murphy JD, Langleben D et al (1985) Congenital diaphragmatic hernia: arterial structural changes and persistent pulmonary hypertension after surgical repair. J Pediatr 107:457–464CrossRefPubMed

16.

Nakazawa N, Takayasu H, Montedonico S et al (2007) Altered regulation of retinoic acid synthesis in nitrofen-induced hypoplastic lung. Pediatr Surg Int 23:391–396CrossRefPubMed

17.

Mey J, Babiuk RP, Clugston R et al (2003) Retinal dehydrogenase-2 is inhibited by compounds that induce congenital diaphragmatic hernias in rodents. Am J Pathol 162:673–679CrossRefPubMedPubMedCentral

18.

Noble BR, Babiuk RP, Clugston RD et al (2007) Mechanisms of action of the congenital diaphragmatic hernia-inducing teratogen nitrofen. Am J Physiol Lung Cell Mol Physiol 293:L1079–L1087CrossRefPubMed

19.

Thébaud B, Tibboel D, Rambaud C et al (1999) Vitamin A decreases the incidence and severity of nitrofen-induced congenital diaphragmatic hernia in rats. Am J Physiol 277(2 Pt 1):L423–L429PubMed

20.

Babiuk RP, Thébaud B, Greer JJ (2004) Reductions in the incidence of nitrofen-induced diaphragmatic hernia by vitamin A and retinoic acid. Am J Physiol Lung Cell Mol Physiol 286:L970–L973CrossRefPubMed

21.

Tzimas G, Nau H, Hendrickx AG et al (1996) Retinoid metabolism and transplacental pharmacokinetics in the cynomolgus monkey following a nonteratogenic dosing regimen with all-trans-retinoic acid. Teratology 54:255–265CrossRefPubMed

22.

Kutasy B, Gosemann JHT et al (2012) Nitrofen interferes with trophoblastic expression of retinol-binding protein and transthyretin during lung morphogenesis in the nitrofen-induced congenital diaphragmatic hernia model. Pediatr Surg Int 28:143–148. doi:10.1007/s00383-011-2995-0 CrossRefPubMed

23.

Major D, Cadenas M, Fournier L et al (1998) Retinol status of newborn infants with congenital diaphragmatic hernia. Pediatr Surg Int 13:547–549CrossRefPubMed

24.

Beurskens LW, Schrijver LH, Tibboel D et al (2013) Dietary vitamin A intake below the recommended daily intake during pregnancy and the risk of congenital diaphragmatic hernia in the offspring. Birth Defects Res A Clin Mol Teratol 97:60–66. doi:10.1002/bdra.23093 CrossRefPubMed

25.

Nakazawa N, Montedonico S, Takayasu H et al (2007) Disturbance of retinol transportation causes nitrofen-induced hypoplastic lung. J Pediatr Surg 42:345–349CrossRefPubMed

26.

Montedonico S, Nakazawa N, Puri P (2006) Retinoic acid rescues lung hypoplasia in nitrofen-induced hypoplastic foetal rat lung explants. Pediatr Surg Int 22:2–8CrossRefPubMed

27.

Doi T, Sugimoto K, Puri P (2009) Prenatal retinoic acid up-regulates pulmonary gene expression of COUP-TFII, FOG2, and GATA4 in pulmonary hypoplasia. J Pediatr Surg 44:1933–1937. doi:10.1016/j.jpedsurg.2009.04.027

28.

Doi T, Sugimoto K, Ruttenstock E et al (2010) Prenatal retinoic acid upregulates pulmonary gene expression of PI3 K and AKT in nitrofen-induced pulmonary hypoplasia. Pediatr Surg Int 26:1011–1015. doi:10.1007/s00383-010-2654-x

29.

Doi T, Sugimoto K, Ruttenstock E et al (2011) Prenatal treatment with retinoic acid activates parathyroid hormone-related protein signaling in the nitrofen-induced hypoplastic lung. Pediatr Surg Int 27:47–52. doi:10.1007/s00383-010-2726-y

30.

Ruttenstock EM, Doi T, Dingemann J et al (2011) Prenatal retinoic acid treatment upregulates late gestation lung protein 1 in the nitrofen-induced hypoplastic lung in late gestation. Pediatr Surg Int 27:125–129. doi:10.1007/s00383-010-2783-2

31.

Ruttenstock EM, Doi T, Dingemann J et al (2011) Prenatal administration of retinoic acid upregulates connective tissue growth factor in the nitrofen CDH model. Pediatr Surg Int 27:573–577. doi:10.1007/s00383-010-2833-9

32.

Ruttenstock E, Doi T, Dingemann J et al (2011) Prenatal administration of retinoic acid upregulates insulin-like growth factor receptors in the nitrofen-induced hypoplastic lung. Birth Defects Res B Dev Reprod Toxicol 92:148–151. doi:10.1002/bdrb.20293

33.

Ruttenstock EM, Doi T, Dingemann J et al (2012) Prenatal retinoic acid upregulates connexin 43 (Cx43) gene expression in pulmonary hypoplasia in the nitrofen-induced congenital diaphragmatic hernia rat model. J Pediatr Surg 47:336–340. doi:10.1016/j.jpedsurg.11.026 CrossRefPubMed

34.

Kutasy B, Friedmacher F, Duess JW et al (2014) Prenatal administration of retinoic acid increases the trophoblastic insulin-like growth factor 2 protein expression in the nitrofen model of congenital diaphragmatic hernia. Pediatr Surg Int 30:137–142. doi:10.1007/s00383-013-3449-7 CrossRefPubMed

35.

Friedmacher F, Fujiwara N, Hofmann AD et al (2014) Prenatal retinoic acid increases lipofibroblast expression in hypoplastic rat lungs with experimental congenital diaphragmatic hernia. J Pediatr Surg 49:876–881. doi:10.1016/j.jpedsurg.2014.01.017 CrossRefPubMed

36.

Friedmacher F, Hofmann AD, Takahashi T et al (2014) Prenatal administration of all-trans retinoic acid upregulates leptin signaling in hypoplastic rat lungs with experimental congenital diaphragmatic hernia. Pediatr Surg Int 30:1183–1190. doi:10.1007/s00383-014-3605-8 CrossRefPubMed

37.

Kitano Y, Kanai M, Davies P et al (2001) BAPS prize-1999: lung growth induced by prenatal tracheal occlusion and its modifying factors: a study in the rat model of congenital diaphragmatic hernia. J Pediatr Surg 36:251–259CrossRefPubMed

38.

Boucherat O, Benachi A, Barlier-Mur AM et al (2007) Decreased lung fibroblast growth factor 18 and elastin in human congenital diaphragmatic hernia and animal models. Am J Respir Crit Care Med 175:1066–1077CrossRefPubMed

39.

Danzer E, Davey MG, Kreiger PA et al (2008) Fetal tracheal occlusion for severe congenital diaphragmatic hernia in humans: a morphometric study of lung parenchyma and muscularization of pulmonary arterioles. J Pediatr Surg 43:1767–1775. doi:10.1016/j.jpedsurg.04.033 CrossRefPubMed

40.

Davey M, Shegu S, Danzer E et al (2007) Pulmonary arteriole muscularization in lambs with diaphragmatic hernia after combined tracheal occlusion/glucocorticoid therapy. Am J Obstet Gynecol 197:381.e1–381.e7

41.

Roubliova XI, Van der Biest AM, Vaast P et al (2008) Effect of maternal administration of betamethasone on peripheral arterial development in fetal rabbit lungs. Neonatology 93:64–72CrossRefPubMed

Titel: Combined antenatal therapy with retinoic acid and tracheal occlusion in a rat model of congenital diaphragmatic hernia
verfasst von: Augusto Frederico Schmidt
Frances Lilian Lanhellas Gonçalves
Rebeca Lopes Figueira
Federico Scorletti
Jose Luis Peiró
Lourenço Sbragia
Publikationsdatum: 18.03.2016
Verlag: Springer Berlin Heidelberg
Erschienen in: Pediatric Surgery International / Ausgabe 6/2016
Print ISSN: 0179-0358
Elektronische ISSN: 1437-9813
DOI: https://doi.org/10.1007/s00383-016-3886-1

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Combined antenatal therapy with retinoic acid and tracheal occlusion in a rat model of congenital diaphragmatic hernia

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Aim

Material and methods

Results

Conclusion

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