A novel surgical toxicological-free model of diaphragmatic hernia in fetal rats

Background Teratogen-induced congenital diaphragmatic hernia (CDH) rat models are commonly used to study the pathophysiology. We have created a new and reliable surgically induced diaphragmatic hernia (DH) model to obtain a purely mechanical DH rat model, and avoid the confounding teratogen-induced...

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Published in:Pediatric research 2022-07, Vol.92 (1), p.118-124
Main Authors: Sbragia, Lourenço, Oria, Marc, Scorletti, Federico, Romero Lopez, Maria del Mar, Schmidt, Augusto F., Levy, Brittany, Peiro, Jose L.
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Language:English
Subjects:
Abdomen
Basic Science Article
Diaphragm (Anatomy)
Fetuses
Hernias
Hospitals
Laboratory animals
Lungs
Medicine
Medicine & Public Health
Pathophysiology
Pediatric Surgery
Pediatrics
Rodents
Thoracic surgery
Thorax
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cited_by cdi_FETCH-LOGICAL-c352t-669dbfb64e1057cb7fe5164ffe0848e3931775c64e9a32b5641dc5ec23e7d90c3
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container_end_page 124
container_issue 1
container_start_page 118
container_title Pediatric research
container_volume 92
creator Sbragia, Lourenço
Oria, Marc
Scorletti, Federico
Romero Lopez, Maria del Mar
Schmidt, Augusto F.
Levy, Brittany
Peiro, Jose L.
description Background Teratogen-induced congenital diaphragmatic hernia (CDH) rat models are commonly used to study the pathophysiology. We have created a new and reliable surgically induced diaphragmatic hernia (DH) model to obtain a purely mechanical DH rat model, and avoid the confounding teratogen-induced effects on the lung development. Methods Fetal DH was surgically created on fetuses at E18.5 and harvested at E21.5 in rats. Four groups were evaluated ( n  = 16): control (CONT), control exposed to Nitrofen (CONT NIT), DH surgically created (DH SURG), and CDH Nitrofen (CDH NIT). Body weight, total lung weights, and their ratio (BW, TLW, and TLBR) were compared. Air space (AS), parenchyma (PA), total protein, and DNA contents were measured to verify lung hypoplasia. Medial wall thickness (MWT) of pulmonary arterioles was also analyzed. Results DH SURG showed significant hypoplasia (decreased in total protein and DNA) vs CONT ( p  
doi_str_mv 10.1038/s41390-021-01702-4
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We have created a new and reliable surgically induced diaphragmatic hernia (DH) model to obtain a purely mechanical DH rat model, and avoid the confounding teratogen-induced effects on the lung development. Methods Fetal DH was surgically created on fetuses at E18.5 and harvested at E21.5 in rats. Four groups were evaluated ( n  = 16): control (CONT), control exposed to Nitrofen (CONT NIT), DH surgically created (DH SURG), and CDH Nitrofen (CDH NIT). Body weight, total lung weights, and their ratio (BW, TLW, and TLBR) were compared. Air space (AS), parenchyma (PA), total protein, and DNA contents were measured to verify lung hypoplasia. Medial wall thickness (MWT) of pulmonary arterioles was also analyzed. Results DH SURG showed significant hypoplasia (decreased in total protein and DNA) vs CONT ( p  &lt; 0.05); DH SURG vs CDH NIT were similar in TLW and TLBR. DH SURG has less AS than CONT ( p  &lt; 0.05) and similar PA compared to CONT NIT and CDH NIT, MWT were similarly increased in CONT NIT, DH SURG, and CDH NIT. Conclusions This novel surgical model generates fetal lung hypoplasia contributing to the study of the mechanical compression effect on fetal lung development in DH. Impact There is a critical need to develop a surgical model in rat to complement the findings of the well-known Nitrofen-induced CDH model. This experimental study is pioneer and can help to understand better the CDH pathophysiological changes caused by herniated abdominal viscera compression against the lung during the final stage of gestation in CDH fetuses, and also to develop more efficient treatments in near future.</description><identifier>ISSN: 0031-3998</identifier><identifier>EISSN: 1530-0447</identifier><identifier>DOI: 10.1038/s41390-021-01702-4</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>Abdomen ; Basic Science Article ; Diaphragm (Anatomy) ; Fetuses ; Hernias ; Hospitals ; Laboratory animals ; Lungs ; Medicine ; Medicine &amp; Public Health ; Pathophysiology ; Pediatric Surgery ; Pediatrics ; Rodents ; Thoracic surgery ; Thorax</subject><ispartof>Pediatric research, 2022-07, Vol.92 (1), p.118-124</ispartof><rights>The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc 2021</rights><rights>The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc 2021.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c352t-669dbfb64e1057cb7fe5164ffe0848e3931775c64e9a32b5641dc5ec23e7d90c3</citedby><cites>FETCH-LOGICAL-c352t-669dbfb64e1057cb7fe5164ffe0848e3931775c64e9a32b5641dc5ec23e7d90c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids></links><search><creatorcontrib>Sbragia, Lourenço</creatorcontrib><creatorcontrib>Oria, Marc</creatorcontrib><creatorcontrib>Scorletti, Federico</creatorcontrib><creatorcontrib>Romero Lopez, Maria del Mar</creatorcontrib><creatorcontrib>Schmidt, Augusto F.</creatorcontrib><creatorcontrib>Levy, Brittany</creatorcontrib><creatorcontrib>Peiro, Jose L.</creatorcontrib><title>A novel surgical toxicological-free model of diaphragmatic hernia in fetal rats</title><title>Pediatric research</title><addtitle>Pediatr Res</addtitle><description>Background Teratogen-induced congenital diaphragmatic hernia (CDH) rat models are commonly used to study the pathophysiology. We have created a new and reliable surgically induced diaphragmatic hernia (DH) model to obtain a purely mechanical DH rat model, and avoid the confounding teratogen-induced effects on the lung development. Methods Fetal DH was surgically created on fetuses at E18.5 and harvested at E21.5 in rats. Four groups were evaluated ( n  = 16): control (CONT), control exposed to Nitrofen (CONT NIT), DH surgically created (DH SURG), and CDH Nitrofen (CDH NIT). Body weight, total lung weights, and their ratio (BW, TLW, and TLBR) were compared. Air space (AS), parenchyma (PA), total protein, and DNA contents were measured to verify lung hypoplasia. Medial wall thickness (MWT) of pulmonary arterioles was also analyzed. Results DH SURG showed significant hypoplasia (decreased in total protein and DNA) vs CONT ( p  &lt; 0.05); DH SURG vs CDH NIT were similar in TLW and TLBR. DH SURG has less AS than CONT ( p  &lt; 0.05) and similar PA compared to CONT NIT and CDH NIT, MWT were similarly increased in CONT NIT, DH SURG, and CDH NIT. Conclusions This novel surgical model generates fetal lung hypoplasia contributing to the study of the mechanical compression effect on fetal lung development in DH. Impact There is a critical need to develop a surgical model in rat to complement the findings of the well-known Nitrofen-induced CDH model. This experimental study is pioneer and can help to understand better the CDH pathophysiological changes caused by herniated abdominal viscera compression against the lung during the final stage of gestation in CDH fetuses, and also to develop more efficient treatments in near future.</description><subject>Abdomen</subject><subject>Basic Science Article</subject><subject>Diaphragm (Anatomy)</subject><subject>Fetuses</subject><subject>Hernias</subject><subject>Hospitals</subject><subject>Laboratory animals</subject><subject>Lungs</subject><subject>Medicine</subject><subject>Medicine &amp; Public Health</subject><subject>Pathophysiology</subject><subject>Pediatric Surgery</subject><subject>Pediatrics</subject><subject>Rodents</subject><subject>Thoracic surgery</subject><subject>Thorax</subject><issn>0031-3998</issn><issn>1530-0447</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><recordid>eNp9kE1LxDAURYMoOI7-AVcFN26q-W67HAa_YGA2ug5p-jKToW3GpBX992amguDC1SMv514eB6Frgu8IZuV95IRVOMeU5JgUmOb8BM2IYGnFeXGKZhgzkrOqKs_RRYw7jAkXJZ-h9SLr_Qe0WRzDxhndZoP_dMa3_vjKbQDIOt8kwtuscXq_DXrT6cGZbAuhdzpzfWZhSMmgh3iJzqxuI1z9zDl6e3x4XT7nq_XTy3Kxyg0TdMilrJra1pIDwaIwdWFBEMmtBVzyEljFSFEIk_4rzWgtJCeNEWAog6KpsGFzdDv17oN_HyEOqnPRQNvqHvwYFRWypIJKzhN68wfd-TH06TpFCywFLiWjiaITZYKPMYBV--A6Hb4UwergWE2OVXKsjo7VoZpNoZjgfgPht_qf1DcVwn4r</recordid><startdate>20220701</startdate><enddate>20220701</enddate><creator>Sbragia, Lourenço</creator><creator>Oria, Marc</creator><creator>Scorletti, Federico</creator><creator>Romero Lopez, Maria del Mar</creator><creator>Schmidt, Augusto F.</creator><creator>Levy, Brittany</creator><creator>Peiro, Jose L.</creator><general>Nature Publishing Group US</general><general>Nature Publishing Group</general><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20220701</creationdate><title>A novel surgical toxicological-free model of diaphragmatic hernia in fetal rats</title><author>Sbragia, Lourenço ; Oria, Marc ; Scorletti, Federico ; Romero Lopez, Maria del Mar ; Schmidt, Augusto F. ; Levy, Brittany ; Peiro, Jose L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c352t-669dbfb64e1057cb7fe5164ffe0848e3931775c64e9a32b5641dc5ec23e7d90c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Abdomen</topic><topic>Basic Science Article</topic><topic>Diaphragm (Anatomy)</topic><topic>Fetuses</topic><topic>Hernias</topic><topic>Hospitals</topic><topic>Laboratory animals</topic><topic>Lungs</topic><topic>Medicine</topic><topic>Medicine &amp; Public Health</topic><topic>Pathophysiology</topic><topic>Pediatric Surgery</topic><topic>Pediatrics</topic><topic>Rodents</topic><topic>Thoracic surgery</topic><topic>Thorax</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sbragia, Lourenço</creatorcontrib><creatorcontrib>Oria, Marc</creatorcontrib><creatorcontrib>Scorletti, Federico</creatorcontrib><creatorcontrib>Romero Lopez, Maria del Mar</creatorcontrib><creatorcontrib>Schmidt, Augusto F.</creatorcontrib><creatorcontrib>Levy, Brittany</creatorcontrib><creatorcontrib>Peiro, Jose L.</creatorcontrib><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health &amp; 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We have created a new and reliable surgically induced diaphragmatic hernia (DH) model to obtain a purely mechanical DH rat model, and avoid the confounding teratogen-induced effects on the lung development. Methods Fetal DH was surgically created on fetuses at E18.5 and harvested at E21.5 in rats. Four groups were evaluated ( n  = 16): control (CONT), control exposed to Nitrofen (CONT NIT), DH surgically created (DH SURG), and CDH Nitrofen (CDH NIT). Body weight, total lung weights, and their ratio (BW, TLW, and TLBR) were compared. Air space (AS), parenchyma (PA), total protein, and DNA contents were measured to verify lung hypoplasia. Medial wall thickness (MWT) of pulmonary arterioles was also analyzed. Results DH SURG showed significant hypoplasia (decreased in total protein and DNA) vs CONT ( p  &lt; 0.05); DH SURG vs CDH NIT were similar in TLW and TLBR. DH SURG has less AS than CONT ( p  &lt; 0.05) and similar PA compared to CONT NIT and CDH NIT, MWT were similarly increased in CONT NIT, DH SURG, and CDH NIT. Conclusions This novel surgical model generates fetal lung hypoplasia contributing to the study of the mechanical compression effect on fetal lung development in DH. Impact There is a critical need to develop a surgical model in rat to complement the findings of the well-known Nitrofen-induced CDH model. This experimental study is pioneer and can help to understand better the CDH pathophysiological changes caused by herniated abdominal viscera compression against the lung during the final stage of gestation in CDH fetuses, and also to develop more efficient treatments in near future.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><doi>10.1038/s41390-021-01702-4</doi><tpages>7</tpages></addata></record>
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subjects Abdomen
Basic Science Article
Diaphragm (Anatomy)
Fetuses
Hernias
Hospitals
Laboratory animals
Lungs
Medicine
Medicine & Public Health
Pathophysiology
Pediatric Surgery
Pediatrics
Rodents
Thoracic surgery
Thorax
title A novel surgical toxicological-free model of diaphragmatic hernia in fetal rats
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