Los genes Hox en la etiología de la hernia diafragmática congénita y la atresia de esófago.

Translated title of the contribution: The etiology of congenital diaphragmatic hernia and esophageal atresia: the Hox genes

L. Martínez, W. Martínez-Calonge, R. Matesanz, V. Fernández-Dumont, F. Pederiva, M. T. Vallejo, J. Salinas, J. A. Tovar

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

BACKGROUND: Prenatal administration of adriamycin or nitrofen to pregnant mice produce in the embryos, respectively, esophageal atresia/VACTERL association (EA) or congenital diaphragmatic hernia (CDH). Various genes and signalling pathways like sonic hedgehog, Gli family, retinoic acid and homeotic genes have been pointed out in the origin of these malformations. Hox genes are master regulatory genes involved in embryo segmentation and other main development processes. Hoxa3, Hoxb3, Hoxc3, Hoxc4 and Hoxa5 knock-out mice show cardiac, tracheal, lung and diaphragmatic malformations, EA and phenotypes that resemble that of VACTERL syndrome. We present herein some of our findings in the expression of these genes in both experimental models. MATERIAL AND METHODS: Pregnant mice were exposed either to 4 mg/kg of adriamycin or vehicle on embryonic days 7,5 and 8,5; embryos were recovered at four endpoints (E13 to 16). On the other hand, nitrofen was given to pregnant mice on embryonic day 8th and embryos were recovered at E14, E16 and E19. The embryos or, separately, their lungs and hearts, were randomly processed for immunohistochemical or molecular biology studies (RT-PCR). We used antibodies for Hoxa3, Hoxb3 and Hoxd3 proteins and specific primers for Hoxa3, Hoxa5, Hoxb3, Hoxb5, Hoxc4 and Hoxd3 genes. RESULTS: EA: Upon immunohistochemistry, adriamycin-exposed embryos showed a severe decrease in expression of Hoxa3, Hoxb3 and Hoxb3 proteins in heart, skin, foregut but not in the heart. RT-PCR studies showed a statistically significant decrease of the four genes studied in the lungs of OA mice when compared to controls. CDH: Upon RT-PCR assessment the expression of Hoxa5 and Hoxb3 were higher in nitrofen-exposed mice than in controls on E14 and E19 and weaker on E16. As regards immunohistochemical localization, expression of the three genes was similar in nitrofen and control animals. CONCLUSIONS: Both experimental models exhibit an alteration in the expression of several proximal Hox genes, specially in lung and car- diac tissues. The malformations in these organs associated with CDH and EA could be in part caused by these alterations. Due to their specific participation in lung and foregut morphogenesis, their study could let us to better understand the mechanisms of CDH and EA.

Original languageSpanish
Pages (from-to)223-228
Number of pages6
JournalCirugia pediatrica : organo oficial de la Sociedad Espanola de Cirugia Pediatrica
Volume20
Issue number4
Publication statusPublished - Oct 2007

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Esophageal Atresia
Homeobox Genes
Embryonic Structures
Lung
Doxorubicin
Polymerase Chain Reaction
Theoretical Models
Genes
Gene Expression
Hedgehogs
Regulator Genes
Tretinoin
Morphogenesis
Knockout Mice
VACTERL association
Congenital Diaphragmatic Hernias
Molecular Biology
Proteins
Immunohistochemistry
Phenotype

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Martínez, L., Martínez-Calonge, W., Matesanz, R., Fernández-Dumont, V., Pederiva, F., Vallejo, M. T., ... Tovar, J. A. (2007). Los genes Hox en la etiología de la hernia diafragmática congénita y la atresia de esófago. Cirugia pediatrica : organo oficial de la Sociedad Espanola de Cirugia Pediatrica, 20(4), 223-228.

Los genes Hox en la etiología de la hernia diafragmática congénita y la atresia de esófago. / Martínez, L.; Martínez-Calonge, W.; Matesanz, R.; Fernández-Dumont, V.; Pederiva, F.; Vallejo, M. T.; Salinas, J.; Tovar, J. A.

In: Cirugia pediatrica : organo oficial de la Sociedad Espanola de Cirugia Pediatrica, Vol. 20, No. 4, 10.2007, p. 223-228.

Research output: Contribution to journalArticle

Martínez, L, Martínez-Calonge, W, Matesanz, R, Fernández-Dumont, V, Pederiva, F, Vallejo, MT, Salinas, J & Tovar, JA 2007, 'Los genes Hox en la etiología de la hernia diafragmática congénita y la atresia de esófago.', Cirugia pediatrica : organo oficial de la Sociedad Espanola de Cirugia Pediatrica, vol. 20, no. 4, pp. 223-228.
Martínez, L. ; Martínez-Calonge, W. ; Matesanz, R. ; Fernández-Dumont, V. ; Pederiva, F. ; Vallejo, M. T. ; Salinas, J. ; Tovar, J. A. / Los genes Hox en la etiología de la hernia diafragmática congénita y la atresia de esófago. In: Cirugia pediatrica : organo oficial de la Sociedad Espanola de Cirugia Pediatrica. 2007 ; Vol. 20, No. 4. pp. 223-228.
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abstract = "BACKGROUND: Prenatal administration of adriamycin or nitrofen to pregnant mice produce in the embryos, respectively, esophageal atresia/VACTERL association (EA) or congenital diaphragmatic hernia (CDH). Various genes and signalling pathways like sonic hedgehog, Gli family, retinoic acid and homeotic genes have been pointed out in the origin of these malformations. Hox genes are master regulatory genes involved in embryo segmentation and other main development processes. Hoxa3, Hoxb3, Hoxc3, Hoxc4 and Hoxa5 knock-out mice show cardiac, tracheal, lung and diaphragmatic malformations, EA and phenotypes that resemble that of VACTERL syndrome. We present herein some of our findings in the expression of these genes in both experimental models. MATERIAL AND METHODS: Pregnant mice were exposed either to 4 mg/kg of adriamycin or vehicle on embryonic days 7,5 and 8,5; embryos were recovered at four endpoints (E13 to 16). On the other hand, nitrofen was given to pregnant mice on embryonic day 8th and embryos were recovered at E14, E16 and E19. The embryos or, separately, their lungs and hearts, were randomly processed for immunohistochemical or molecular biology studies (RT-PCR). We used antibodies for Hoxa3, Hoxb3 and Hoxd3 proteins and specific primers for Hoxa3, Hoxa5, Hoxb3, Hoxb5, Hoxc4 and Hoxd3 genes. RESULTS: EA: Upon immunohistochemistry, adriamycin-exposed embryos showed a severe decrease in expression of Hoxa3, Hoxb3 and Hoxb3 proteins in heart, skin, foregut but not in the heart. RT-PCR studies showed a statistically significant decrease of the four genes studied in the lungs of OA mice when compared to controls. CDH: Upon RT-PCR assessment the expression of Hoxa5 and Hoxb3 were higher in nitrofen-exposed mice than in controls on E14 and E19 and weaker on E16. As regards immunohistochemical localization, expression of the three genes was similar in nitrofen and control animals. CONCLUSIONS: Both experimental models exhibit an alteration in the expression of several proximal Hox genes, specially in lung and car- diac tissues. The malformations in these organs associated with CDH and EA could be in part caused by these alterations. Due to their specific participation in lung and foregut morphogenesis, their study could let us to better understand the mechanisms of CDH and EA.",
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T1 - Los genes Hox en la etiología de la hernia diafragmática congénita y la atresia de esófago.

AU - Martínez, L.

AU - Martínez-Calonge, W.

AU - Matesanz, R.

AU - Fernández-Dumont, V.

AU - Pederiva, F.

AU - Vallejo, M. T.

AU - Salinas, J.

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N2 - BACKGROUND: Prenatal administration of adriamycin or nitrofen to pregnant mice produce in the embryos, respectively, esophageal atresia/VACTERL association (EA) or congenital diaphragmatic hernia (CDH). Various genes and signalling pathways like sonic hedgehog, Gli family, retinoic acid and homeotic genes have been pointed out in the origin of these malformations. Hox genes are master regulatory genes involved in embryo segmentation and other main development processes. Hoxa3, Hoxb3, Hoxc3, Hoxc4 and Hoxa5 knock-out mice show cardiac, tracheal, lung and diaphragmatic malformations, EA and phenotypes that resemble that of VACTERL syndrome. We present herein some of our findings in the expression of these genes in both experimental models. MATERIAL AND METHODS: Pregnant mice were exposed either to 4 mg/kg of adriamycin or vehicle on embryonic days 7,5 and 8,5; embryos were recovered at four endpoints (E13 to 16). On the other hand, nitrofen was given to pregnant mice on embryonic day 8th and embryos were recovered at E14, E16 and E19. The embryos or, separately, their lungs and hearts, were randomly processed for immunohistochemical or molecular biology studies (RT-PCR). We used antibodies for Hoxa3, Hoxb3 and Hoxd3 proteins and specific primers for Hoxa3, Hoxa5, Hoxb3, Hoxb5, Hoxc4 and Hoxd3 genes. RESULTS: EA: Upon immunohistochemistry, adriamycin-exposed embryos showed a severe decrease in expression of Hoxa3, Hoxb3 and Hoxb3 proteins in heart, skin, foregut but not in the heart. RT-PCR studies showed a statistically significant decrease of the four genes studied in the lungs of OA mice when compared to controls. CDH: Upon RT-PCR assessment the expression of Hoxa5 and Hoxb3 were higher in nitrofen-exposed mice than in controls on E14 and E19 and weaker on E16. As regards immunohistochemical localization, expression of the three genes was similar in nitrofen and control animals. CONCLUSIONS: Both experimental models exhibit an alteration in the expression of several proximal Hox genes, specially in lung and car- diac tissues. The malformations in these organs associated with CDH and EA could be in part caused by these alterations. Due to their specific participation in lung and foregut morphogenesis, their study could let us to better understand the mechanisms of CDH and EA.

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