Conduction system abnormalities in rat embryos induced by maternal hyperthermia

Aoyama, Naoyoshi; Yamashina, Shohei; Poelmann, Robert E.; Groot, Adriana C. Gittenberger‐de; Izumi, Tohru; Soma, Kazui; Ohwada, Takashi

doi:10.1002/ar.10101

Cited by 6 publications

(6 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One possible explanation for the sensitivity of cells in the conduction pathway to corticosteroid exposure is that like neurons, Purkinje fibers are susceptible to cellular stress. Studies in rat embryos showed that maternal hyperthermia caused malformations in both the central nervous system and cardiac conduction system (6). Although Purkinje fiber development has not been as thoroughly studied in the ovine fetus in terms of factors inducing Purkinje fiber maturation, structural studies of the ovine heart show that the time of our treatment corresponds to the end of the development of a fibrous sheath around the septal Purkinje fibers and the beginning of the ensheathment of the ventricular Purkinje fibers; formation of this sheath is complete, well organized, and dense by gestational day 140, but nonexistent at day 115 (12).…”

Section: Discussionmentioning

confidence: 99%

Cortisol stimulates proliferation and apoptosis in the late gestation fetal heart: differential effects of mineralocorticoid and glucocorticoid receptors

Feng

Reini

Richards

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

We have previously found that modest chronic increases in maternal cortisol result in an enlarged fetal heart. To explore the mechanisms of this effect, we used intrapericardial infusions of a mineralocorticoid receptor (MR) antagonist (canrenoate) or of a glucocorticoid receptor (GR) antagonist (mifepristone) in the fetus during maternal infusion of cortisol (1 mg·kg⁻¹·day⁻¹). We have shown that the MR antagonist blocked the increase in fetal heart weight and in wall thickness resulting from maternal cortisol infusion. In the current study we extended those studies and found that cortisol increased Ki67 staining in both ventricles, indicating cell proliferation, but also increased active caspase-3 staining in cells of the conduction pathway in the septum and subendocardial layers of the left ventricle, suggesting increased apoptosis in Purkinje fibers. The MR antagonist blocked the increase in cell proliferation, whereas the GR antagonist blocked the increased apoptosis in Purkinje fibers. We also found evidence of activation of caspase-3 in c-kit-positive cells, suggesting apoptosis in stem cell populations in the ventricle. These studies suggest a potentially important role of corticosteroids in the terminal remodeling of the late gestation fetal heart and suggest a mechanism for the cardiac enlargement with excess corticosteroid exposure.

show abstract

Section: Discussionmentioning

confidence: 99%

Cortisol stimulates proliferation and apoptosis in the late gestation fetal heart: differential effects of mineralocorticoid and glucocorticoid receptors

Feng

Reini

Richards

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

show abstract

“…Interestingly, in our model of Zn deficiency, we show reduced HNK-1 expression in the heart, in regions that are in close proximity of certain components of the CCS (namely, the SAN and AVN). The interpretation of these results is challenging as HNK-1 has been used to probe both the NCC and the components of the CCS [53][54][55][56][57][58][59][60][61].…”

Section: Discussionmentioning

confidence: 99%

“…In our work, we assessed Cx43 expression as an indicator of cardiac NCC populating the heart, whereas SMA staining was used to trace the abundance of NCC-derived smooth muscle cells [50][51][52]. We also determined the changes in HNK-1 staining distribution and intensity, as this sulfated carbohydrate epitope is also expressed by NCC; however, in the rats, HNK-1 has also been used as a probe for the components of the cardiac conduction system (CCS) as well [53][54][55][56][57][58][59][60][61]. Finally, because they potentially may be influenced by Zn status, we monitored the expression of GATA-4 and FOG-2, two Zn-finger transcription factors that regulate the expression of a variety of structural and regulatory genes, critical for cardiac morphogenesis [62][63][64], but are not associated with cardiac NCC patterning and function.…”

Section: Introductionmentioning

confidence: 99%

Prenatal Zinc Deficiency: Influence on Heart Morphology and Distribution of Key Heart Proteins in a Rat Model

López

Keen

Lanoue

2008

Biol Trace Elem Res

View full text Add to dashboard Cite

The etiology of congenital heart disease is multifactorial, with genetics and nutritional deficiencies recognized as causative agents. Maternal zinc (Zn) deficiency is associated with an increased risk for fetal heart malformations; however, the contributing mechanisms have yet to be identified. In this study, we fed pregnant rats a Zn-adequate diet (ZnA), a Zn-deficient (ZnD), or a restricted amount of Zn adequate diet (RF) beginning on gestation day (GD) 4.5, to examine whether increased cell death and changes in cardiac neural crest cells (NCC) play a role in Zn deficiency-induced heart defects. Fetuses were collected on GD 13.5, 15.5, and 18.5 and processed for GATA-4, FOG-2, connexin-43 (Cx43), HNK-1, smooth muscle alpha-actin (SMA) and cleaved caspase-3 protein expression. Fetuses from ZnA-fed dams showed normal heart development, whereas fetuses from dams fed with the ZnD diet exhibited a variety of heart anomalies, particularly in the region of the outflow tract. HNK-1 expression was lower than normal in the hearts of GD13.5 and 15.5 ZnD fetuses, particularly in the right atrium and in the distal tip of the interventricular septum. Conversely, Cx43 immunoreactivity was increased throughout the heart in fetuses from ZnD dams compared to fetuses from control dams. The distribution and intensity of expression of SMA, GATA-4, FOG-2, and markers of apoptosis were similar among the three groups. We propose that Zn deficiency induced alterations in the distribution of Cx43 and HNK-1 in fetal hearts contribute to the occurrence of the developmental heart anomalies.

show abstract

“…Over the last century, most of the studies investigating the teratogenic effects of increased maternal body temperature have reported a preponderance of central nervous system (CNS) defects, suggesting that the CNS is more susceptible than other organ systems Jessop, 1959, 1963;Hakosalo and Saxen, 1971;Miller et al, 1978;Layde et al, 1980;Shiota, 1982;Milunsky et al, 1992;Zhang and Cai, 1993;Suarez et al, 2004;Li et al, 2007;). Indeed, other malformations such as oral clefts, micropthalmia, cerebral palsy, and talipes equinovarus (clubfoot) have been reported infrequently (Edwards, 1971;Smith et al, 1978;Hendrickx et al, 1979;Pleet et al, 1981;Shiota, 1982;Nilsen, 1984;Germain et al, 1985;Aoyama et al, 2002). Because the teratogenic effects of increased body temperatures are probably not limited to a specific birth defect, infants exposed in utero to a hyperthermic environment might have more than one birth defect, depending on the gestational period as well as duration and intensity of the hyperthermic exposure (Edwards, 2006).…”

Section: Maternal Fever and Oral Cleftsmentioning

confidence: 99%

Maternal fever during early pregnancy and the risk of oral clefts

Hashmi¹,

Gallaway

Waller

et al. 2010

Birth Defects Research

View full text Add to dashboard Cite

An increased risk of birth defects after hyperthermic exposures has been confirmed in animal studies, but population studies have yielded inconsistent results. Oral clefts are a common birth defect and have been associated with these exposures in some of these studies. In this study, data from the National Birth Defects Prevention Study was used to evaluate the association of maternal report of febrile illness in early pregnancy and the risk of oral clefts. All oral cleft cases born between 1997 and 2004 were compared with nonmalformed controls born in the same geographical region during the same time period. Mothers reporting febrile illness during pregnancy were stratified by fever grade and antipyretic use. Logistic regression models were used to generate crude and adjusted odds ratios for exposure to fever and association with each oral cleft phenotype. The dataset included 5821 controls, 1567 cases of cleft lip with or without cleft palate (CL+/-P) and 835 cases of cleft palate only. A modestly increased risk was observed for isolated CL+/-P (odds ratio, 1.28; 95% confidence interval, 1.01-1.63). Stratification by fever grade (body temperature <101.5 degrees or > or =101.5 degrees F) did not yield significant differences in risk. Risk estimates were higher among women who reported a fever, but did not take antipyretics to control their fever, particularly for nonisolated compared with isolated oral clefts. This finding suggests that adequate control of fever may diminish the deleterious effects of fever in cases of oral cleft.

show abstract

Conduction system abnormalities in rat embryos induced by maternal hyperthermia

Cited by 6 publications

References 30 publications

Cortisol stimulates proliferation and apoptosis in the late gestation fetal heart: differential effects of mineralocorticoid and glucocorticoid receptors

Cortisol stimulates proliferation and apoptosis in the late gestation fetal heart: differential effects of mineralocorticoid and glucocorticoid receptors

Prenatal Zinc Deficiency: Influence on Heart Morphology and Distribution of Key Heart Proteins in a Rat Model

Maternal fever during early pregnancy and the risk of oral clefts

Contact Info

Product

Resources

About