Alcohol exposure during pregnancy causes non-compaction cardiomyopathy in offspring mice

Huiming ZHOU; Kunfeng JIANG; Tiewei LYU; Lingjun LIU; Jie TIAN

doi:10.16016/j.1000-5404.201702133

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Alcohol exposure during pregnancy causes non-compaction cardiomyopathy in offspring mice

Basic Medicine | 更新时间：2026-01-09

- Alcohol exposure during pregnancy causes non-compaction cardiomyopathy in offspring mice
- Journal of Third Military Medical University Vol. 39, Issue 17, Pages: 1696-1701(2017)
- 作者机构：
  
  400014 重庆，重庆医科大学附属儿童医院心内科，儿童发育疾病研究教育部重点实验室，儿童发育重大疾病国家国际科技合作基地，儿科学重庆市重点实验室
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(81270234);the General Program of National Natural Science Foundation of China(81570218)
- DOI：10.16016/j.1000-5404.201702133
  CLC： R322.11;R541;R715.3
- Received：23 February 2017，
  
  Revised：2017-05-01，
  
  Published：15 September 2017
- 稿件说明：
移动端阅览
Huiming ZHOU, Kunfeng JIANG, Tiewei LYU, et al. Alcohol exposure during pregnancy causes non-compaction cardiomyopathy in offspring mice[J]. Journal of Third Military Medical University, 2017, 39(17): 1696-1701.
DOI：

Huiming ZHOU, Kunfeng JIANG, Tiewei LYU, et al. Alcohol exposure during pregnancy causes non-compaction cardiomyopathy in offspring mice[J]. Journal of Third Military Medical University, 2017, 39(17): 1696-1701. DOI： 10.16016/j.1000-5404.201702133.

摘要

目的

探讨孕期酒精暴露致子代小鼠心肌致密化不全样改变的关系。

方法

对孕期3.5～18.5 d的母鼠用56%酒精以5 mL/kg的剂量灌胃，收集孕期第19.5天子代小鼠心脏标本，电子透射显微镜观察肌丝、线粒体及肌浆网等心肌细胞超微结构，HE染色观察心室肌层结构，小鼠心脏超声心动图观察成年鼠心脏舒缩功能及心室肌层改变。

结果

实验组子代心脏电镜下发现肌丝排列紊乱、溶解的现象; 31.25%子代小鼠(5/16) 的左心室肌呈非致密化样改变[病变组N/C值为(2.49±0.68)

对照组N/C值为(0.62±0.23)；

=10.397，

=0.000

]

，且心脏体积变小，病变室腔明显扩大; 成年后心脏超声提示实验组小鼠心功能减退、室间隔/左室后壁增厚。

结论

孕期大量酒精暴露可致子代小鼠心室肌出现高度肌小梁化及心肌压实缺乏等改变，孕期酗酒可能是子代心肌致密化不全的病因之一。

Abstract

Objective

To investigate the relationship of alcohol exposure during pregnancy and non-compaction cardiomyopathy (NCC) in offspring mice.

Methods

Pregnant mice of ED3.5-ED18.5 were given 56% alcohol by gavage at a dose of 5 mL/kg. The ED19.5 mice were sacrificed

and the heart of the fetal mice was harvested. Transmission electron microscopy (filaments

mitochondria and sarcoplasmic reticulum) and HE staining were used to verify the changes of structure and ultrastructure of the obtained myocardial tissues. Echocardiography was used to evaluate the cardiac function and ventricular myometrium of the offspring mice after growing up.

Results

Alcohol exposure during pregnancy caused the disorganized and dissolved myofilaments in the fetal mice. Some offspring mice (31.25%

5/16) had NCC. The ratio of non-compacted myocardium to compact myocardium at the end of systole (N/C) was 2.49±0.6 in the offspring mice of the alcohol exposure group

significantly higher than that in the control offspring mice (0.62±0.23

=10.397

=0.000). The volume of heart was decreased in the offspring mice of the alcohol exposure group while the left ventricule was enlarged. Echocardiography showed cardiac dysfunction and thickened ventricular septal/left ventricular posterior walls in the grown-up mice of the exposure group.

Conclusion

Large dose of alcohol exposure during pregnancy cause trabeculations and non-compaction in ventricular myocardium

and it might be one of causers for NCC in the offspring.

关键词

Keywords

references

MARON B J, TOWBIN J A, THIENE G, et al. Contemporary definitions and classification of the cardiomyopathies[J]. Circulation, 2006, 113(14):1807-1816. DOI: 10.1161/CIRCULATIONAHA.106.174287.

ZHANG W, CHEN H, QU X, et al. Molecular mechanism of ventricular trabeculation/compaction and the pathogenesis of the left ventricular noncompaction cardiomyopathy(LVNC)[J]. Am J Med Genet C Semin Med Genet, 2013, 163C(3): 144-156. DOI:10.1002/ajmg.c.31369.

LIU X, LIU W L. Research progress of the left ventricular non-compaction cardiomyopathy[J]. Chinese Circulation Journal. 2016, 31(2): 198-200. DOI:10.3969/j.issn.1000-3614.2016.02.023.

SCHWEIZER P A, SCHROTER J, GREINER S, et al. The symptom complex of familial sinus node dysfunction and myocardial noncompaction is associated with mutations in the HCN4 channel[J]. J Am Coll Cardiol, 2014, 64(8): 757-767. DOI:10.1016/j.jacc.2014.06.1155.

KARUNAMUNI G, GU S, DOUGHMAN Y Q, et al. Using optical coherence tomography to rapidly phenotype and quantify congenital heart defects associated with prenatal alcohol exposure[J]. Dev Dyn, 2015, 244(4): 607-618. DOI:10.1002/dvdy.24246.

SARMAH S, MARRS J A. Complex cardiac defects after ethanol exposure during discrete cardiogenic events in zebrafish: prevention with folic acid[J]. Dev Dyn, 2013, 242(10): 1184-1201. DOI:10.1002/dvdy.24015.

JENNI R, OECHSLIN E, SCHNEIDER J, et al. Echocardiographic and pathoanatomical characteristics of isolated left ventricular non-compaction: a step towards classification as a distinct cardiomyopathy[J]. Heart, 2001, 86(6): 666-671. DOI:10.1136/heart.86.6.666.

PIGNATELLI R H, MCMAHON C J, DREYER W J, et al. Clinical characterization of left ventricular noncompaction in children: a relatively common form of cardiomyopathy[J]. Circulation, 2003, 108(21): 2672-2678. DOI:10.1161/01.CIR.0000100664.10777.B8.

ROSS C P, PERSAUD T V. Cardiovascular primordium of the rat embryo following in utero exposure to alcohol and caffeine[J]. Can J Cardiol, 1986, 2(3): 160-163.

SERRANO M, HAN M, BRINEZ P, et al. Fetal alcohol syndrome: cardiac birth defects in mice and prevention with folate[J].Am J Obstet Gynecol, 2010, 203(1): 75-77. DOI:10.1016/j.ajog.2010.03.017.

PAN B, ZHU J, LV T, et al. Alcohol consumption during gestation causes histone3 lysine9 hyperacetylation and an alternation of expression of heart development-related genes in mice[J]. Alcohol Clin Exp Res, 2014, 38(9): 2396-2402. DOI:10.1111/acer.12518.

SAMSA L A, YANG B, LIU J. Embryonic cardiac chamber maturation: trabeculation, conduction, and cardiomyocyte proliferation[J]. Am J Med Genet C Semin Med Genet, 2013, 163C(3): 157-168. DOI:10.1002/ajmg.c.31366.

GUNDOGAN F, GILLIGAN J, QI W, et al. Dose effect of gestational ethanol exposure on placentation and fetal growth[J]. Placenta, 2015, 36(5): 523-530. DOI:10.1016/j.placenta.2015.02.010.

PENG C, ZHANG W, ZHAO W, et al. Alcohol-induced histone H3K9 hyperacetylation and cardiac hypertrophy are reversed by a histone acetylases inhibitor anacardic acid in developing murine hearts[J]. Biochimie, 2015, 113: 1-9. DOI:10.1016/j.biochi.2015.03.012.

HAGHIGHI POODEH S, SALONURMI T, NAGY I, et al. Alcohol-induced premature permeability in mouse placenta-yolk sac barriers in vivo [J]. Placenta, 2012, 33(10): 866-873. DOI:10.1016/j.placenta.2012.07.008.

FATKIN D, SEIDMAN C E, SEIDMAN J G. Genetics and disease of ventricular muscle[J]. Cold Spring Harb Perspect Med, 2014, 4(1): a021063. DOI:10.1101/cshperspect.a021063.

NGUYEN V B, PROBYN M E, CAMPBELL F, et al. Low-dose maternal alcohol consumption: effects in the hearts of offspring in early life and adulthood[J]. Physiol Rep, 2014, 2(7):e12087. DOI: 10.14814/phy2.12087.

SEDMERA D, PEXIEDER T, VUILLEMIN M, et al. Developmental patterning of the myocardium[J]. Anat Rec, 2000, 258(4): 319-337.

ZHANG W, PENG C, ZHENG M, et al. Prenatal alcohol exposure causes the over-expression of DHAND and EHAND by increasing histone H3K14 acetylation in C57 BL/6 mice[J]. Toxicol Lett, 2014, 228(3):140-146. DOI: 10.1016/j.toxlet.2014.05.011.

NEILL C A. Genetics of congenital heart disease[J]. Annu Rev Med, 1973, 24: 61-66. DOI:10.1146/annurev.me.24.020173.000425.

BRESCIA S T, ROSSANO J W, PIGNATELLI R, et al. Mortality and sudden death in pediatric left ventricular noncompaction in a tertiary referral center[J]. Circulation, 2013, 127(22): 2202-2208. DOI:10.1161/CIRCULATIONAHA.113.002511.

XU Y M. Clinical features of 123 cases children with non-compaction cardiomyopathy[J]. Chinese Journal of Practical Pediatrics. 2010, 25(6):472-77.DOI: 1005-2224(2010)06-0472-04.

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