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Updated: Aug 19, 2026
Murine Fetal Echocardiography
Published on: February 15, 2013
Effect of maternal autoantibodies on fetal cardiac conduction: an experimental murine model
Hiroshi Suzuki1, Earl D Silverman, Xuejun Wu
1Division of Cardiovascular Research, The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.
Insights
Maternal immunization with Ro, La, or calreticulin autoantigens induced fetal heart block in mice. Early embryonic Doppler echocardiography revealed significant fetal bradycardia and atrioventricular block, often missed at birth.
Area of Science:
- Immunology
- Cardiology
- Developmental Biology
Background:
- Congenital heart block (CHB) pathogenesis is poorly understood.
- Existing murine models for CHB have limitations due to fetal wastage.
- Assessing atrioventricular conduction solely at birth may miss crucial developmental damage.
Purpose of the Study:
- To develop a more responsive murine model for CHB.
- To utilize embryonic Doppler echocardiography for observing fetal conduction system damage.
- To investigate the immune response to specific autoantigens in CHB development.
Main Methods:
- Mature female C3H/HeJ mice were immunized with 60 kD Ro, 48 kD La, or recombinant calreticulin autoantigens.
- Serum autoantibodies were confirmed via ELISA.
- Fetal heart rate and atrioventricular block (AVB) were monitored using embryonic Doppler echocardiography from 13 days of gestation.
Main Results:
- All immunized groups developed significant serum autoantibodies.
- Immunized groups showed significantly lower fetal heart rates and higher incidences of fetal bradycardia/AVB compared to controls.
- Nonadvanced second-degree AVB occurred in 9-18% of fetuses in immunized groups by 18 days gestation, with only first-degree AVB observed neonatally.
Conclusions:
- Maternal immunization with Ro, La, or calreticulin autoantigens successfully induced AVB in a significant percentage of fetuses.
- Early embryonic assessment is critical as lesser degrees of AVB are present at birth.
- This model and methodology can improve understanding of CHB pathogenesis and fetal wastage.
Abstract:
The pathogenesis of congenital heart block (CHB) remains unclear. The occurrence rate of neonatal CHB is low, even in murine models of lupus erythematosus. The assessment of heart block in murine maternal lupus models by measuring atrioventricular conduction in neonatal offspring is potentially confounded by fetal wastage. We therefore sought to develop a murine CHB model with a superior immune response and to use embryonic Doppler echocardiography to observe conduction system damage in the fetus. Mature 8-wk-old female C3H/HeJ mice (n=43) were immunized with 60 kD Ro, 48 kD La, or recombinant calreticulin autoantigens. ELISA confirmed that significant serum autoantibodies developed in all three immunized groups when compared with controls. Starting at 13 d of gestation, a significantly lower fetal heart rate (HR) and a higher percentage of fetal bradycardia/atrioventricular block (AVB, nonadvanced second degree) were observed in all immunized groups, compared with controls. There was 9-18% nonadvanced second-degree AVB in immunized groups and 0% in controls at <18 d of gestation. Neonatal electrocardiograms demonstrated only 1 degrees AVB in immunized groups. Maternal immunization with 60 kD Ro, 48 kD La, or recombinant calreticulin autoantigens resulted in AVB in a significant percentage of fetuses, however, lesser degrees of AVB were seen at birth. Significant fetal bradycardia and AVB may be missed by assessment only at birth in murine models of CHB due to fetal wastage.
