Effects of prenatal vitamins A, E, and C on the hypoplastic hearts of fetal rats with diaphragmatic hernia

González-Reyes, Salomé; Martínez, Leopoldo; Tovar, Juan A.

doi:10.1016/j.jpedsurg.2005.05.009

Cited by 15 publications

(8 citation statements)

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“…Regarding potential fetal adverse effects, the nitrofen-exposed pups presented decrease of HW/BW and KW/BW ratios as previously documented (10,(61)(62)(63). On the other hand, PD-123319 beneficial effect seemed lungspecific, since HW/BW and KW/BW ratios of the pups were not altered.…”

Section: Discussionsupporting

confidence: 77%

Local Fetal Lung Renin-Angiotensin System as a Target to Treat Congenital Diaphragmatic Hernia

Nogueira‐Silva

Carvalho-Dias

Piairo

et al. 2011

Mol Med

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Antenatal stimulation of lung growth is a reasonable approach to treat congenital diaphragmatic hernia (CDH), a disease characterized by pulmonary hypoplasia and hypertension. Several evidences from the literature demonstrated a possible involvement of renin-angiotensin system (RAS) during fetal lung development. Thus, the expression pattern of renin, angiotensin-converting enzyme, angiotensinogen, type 1 (AT 1 ) and type 2 (AT 2 ) receptors of angiotensin II (ANGII) was assessed by immunohistochemistry throughout gestation, whereas the function of RAS in the fetal lung was evaluated using fetal rat lung explants. These were morphometrically analyzed and intracellular pathway alterations assessed by Western blot. In nitrofen-induced CDH model, pregnant rats were treated with saline or PD-123319. In pups, lung growth, protein/DNA ratio, radial saccular count, epithelial differentiation and lung maturation, vascular morphometry, right ventricular hypertrophy and overload molecular markers, gasometry and survival time were evaluated. Results demonstrated that all RAS components were constitutively expressed in the lung during gestation and that ANGII had a stimulatory effect on lung branching, mediated by AT 1 receptor, through p44/42 and Akt phosphorylation. This stimulatory effect on lung growth was mimicked by AT 2 -antagonist (PD-123319) treatment. In vivo antenatal PD-123319 treatment increased lung growth, ameliorated indirect parameters of pulmonary hypertension, improved lung function and survival time in nonventilated CDH pups, without maternal or fetal deleterious effects. Therefore, this study demonstrated a local and physiologically active RAS during lung morphogenesis. Moreover, selective inhibition of AT 2 receptor is presented as a putative antenatal therapy for CDH.

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Section: Discussionsupporting

confidence: 77%

Local Fetal Lung Renin-Angiotensin System as a Target to Treat Congenital Diaphragmatic Hernia

Nogueira‐Silva

Carvalho-Dias

Piairo

et al. 2011

Mol Med

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“…It has been shown that other antioxidant vitamins (C and E) diminish the effects of nitrofen in exposed rats or in human cultured pneumocytes [52,53]. Our group showed that vitamin A induced significant improvement of heart hypoplasia in nitrofen-exposed rats in terms of incidence of malformations, weight, total DNA content, and balance of proliferation and apoptosis at the end of gestation [23,54]. Cx43 is undoubtedly involved in the pathogenesis of heart anomalies in experimental CDH and vitamin A has a positive influence on them.…”

Section: Discussionmentioning

confidence: 67%

Expression of Connexin 43 in the hearts of rat embryos exposed to nitrofen and effects of vitamin A on it

et al. 2005

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Rats with experimental congenital diaphragmatic hernia (CDH) have heart hypoplasia and conotruncal and great vessel malformations that are likely related to disturbed neural crest developmental control. Neural crest cells communicate through intercellular gap junctions whose main protein is Connexin 43 (Cx43). The migration and participation of neural crest cells in heart development is likely influenced by this protein which might be also directly involved in myocardial development. Vitamin A is beneficial for heart hypoplasia in CDH rats. The aims of this study were to examine the status of Cx43 in the heart of embryonal rats exposed to nitrofen and to assess if vitamin A reverts these effects. Pregnant rats received either 100 mg nitrofen or olive oil on E9.5. Each group was divided into two subgroups according to the subsequent treatment with intragastric vitamin A (15,000 i.u.) or vehicle on E10.5 and E11.5. The pups were recovered on E13, E15, and E21 and the hearts were dissected out and pooled. Cx43 mRNA expression was determined by quantitative real-time PCR. Comparisons among groups were made with ANOVA and Bonferroni post hoc tests with a threshold of significance of P<0.05. In control rats Cx43 mRNA was minimally expressed on E13 and E15 and fully expressed on E21. Nitrofen significantly increased Cx43 mRNA on E15. Additional treatment with vitamin A tended to moderate this increase on E15. Cx43 was overexpressed in the hearts of nitrofen-exposed embryonal rats on day E15 of gestation. Vitamin A tended to normalize this expression. The mechanism of action of Cx43 deserves further investigation.

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“…There is also evidence that Pax 3 is altered in response to nitrofen, which in turn disrupts normal neural crest cell signaling and migration. Nitrofen-treated embryos showed a significant reduction in the amount of Pax3 mRNA [59]. In a similar study, nitrofen-treated embryos showed decreased expression of the angiotensin II receptor type 1 (AT1), type 2 (AT2) and TGF 1 mRNA levels, suggesting that downregulation of the rennin-angiotensin system may be involved in the pathogenesis of cardiac hypoplasia in nitrofen-induced CDH [62].…”

Section: Whole Embryo Culture Assaymentioning

confidence: 74%

“…There is growing literature that indicates many harmful teratogens produce cardiac malformations. Alcohol and nitrofen are examples of such teratogens [56][57][58][59][60][61]. Nitrofen (2,4-dichlorophenyl-p-nitrophenyl ether) is known to cause congenital diaphragmatic hernia (CDH) in rodent models.…”

Section: Whole Embryo Culture Assaymentioning

confidence: 99%

Modeling Cardiovascular Development: New Approaches are Making In Vitro En Vogue

Goodwin¹,

Yost²,

Potts³

2006

CCR

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In vitro models have proven themselves to be powerful allies with in vivo models for the dissection of the molecular mechanisms of cardiovascular development. The purpose of this manuscript is to review the advances that have enabled the creation of a new generation of in vitro models. These advances include the advent of new biomaterials and cell scaffolds that have provided the opportunity to design niches where developmental processes can occur under controlled, in vitro conditions. The engineering of biomaterials, along with new imaging capabilities, are being applied to important developmental questions. These interdisciplinary approaches promise to accelerate the identification of the molecular processes that regulate the cell-cell and cell-extracellular matrix (ECM) interactions that occur during the development of cardiac tissues. These new models not only offer the opportunity to test molecular mechanisms but also provide morphogenetic assays where the development of functional cardiovascular tissues can be achieved. The advent of these technologies is far reaching: from the ability to engineer functional cardiovascular tissues to the rational implantation of cell therapies for cardiovascular disease.Key Words: Cardiac development, tissue engineering, in vitro models. PURPOSE AND SCOPEIn recent years, a great deal of progress has been made in determining many of the factors that regulate cardiovascular development. This progress has been accomplished through the use of both in vivo and in vitro models. Although in vivo models are critically important, their inherent complexity can confound experimental analysis. On the other hand, the advantage of in vitro models lies largely in the ability to control the number of experimental variables. Their application can be limited, however. These limitations are dependent on the fidelity to which they model the intended process. Recently described models presented in this review offer the ability to extend the applicability of in vitro models by making them more relevant to cardiovascular development in vivo.For the purposes of this review, in vitro development is defined as development that takes place under artificial conditions. This could be interpreted to include transgenic and knockout approaches; however, this review will exclude those techniques in which development occurs in utero. Likewise, models using Xenopus laevis and Zebrafish will not be discussed in detail. These models have added tremendously to the body of knowledge of cardiovascular biology but do not appear to require complex culturing techniques that will be discussed here. Why developing amniotes require specialized culture conditions is an intriguing question, but will not be addressed here. Specifically, we will focus on emerging in vitro models and how they can be used to investigate fundamental questions of cardiovascular development including coronary vessel development, the role of physical forces, fibroblast/myocyte interactions and late valve formation.This review is divided into thr...

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Effects of prenatal vitamins A, E, and C on the hypoplastic hearts of fetal rats with diaphragmatic hernia

Cited by 15 publications

References 40 publications

Local Fetal Lung Renin-Angiotensin System as a Target to Treat Congenital Diaphragmatic Hernia

Local Fetal Lung Renin-Angiotensin System as a Target to Treat Congenital Diaphragmatic Hernia

Expression of Connexin 43 in the hearts of rat embryos exposed to nitrofen and effects of vitamin A on it

Modeling Cardiovascular Development: New Approaches are Making In Vitro En Vogue

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