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Updated: Oct 10, 2025
Analysis of Electrocardiograms and Behavior in Mice from Pregnancy to Lactation Period
Published on: April 5, 2024
Effect of Valproic Acid on Maternal - Fetal Heart Rates and Coupling in Mice on Embryonic day 15.5 (E15.5)
Insights
Prenatal valproic acid (VPA) exposure disrupts maternal-fetal heart rate coupling in mice, potentially impacting fetal cardiac development. This study highlights VPA
Area of Science:
- Developmental biology
- Cardiovascular physiology
- Neuroscience
Background:
- Prenatal valproic acid (VPA) exposure is linked to fetal cardiac anomalies and autism spectrum disorder (ASD).
- VPA is a crucial treatment for epilepsy and neurological disorders.
- The impact of VPA on maternal-fetal heart rate (HR) coupling remains largely unknown.
Purpose of the Study:
- To investigate the effects of prenatal VPA exposure on maternal-fetal HR coupling patterns in a mouse model.
- To analyze cardiac rhythm interactions between mother and fetus at embryonic day 15.5 (E15.5).
Main Methods:
- Pregnant mice received VPA or saline from E12.5.
- Electrocardiogram (ECG) recordings were obtained from mothers and fetuses at E15.5.
- Analysis included mean RR intervals, coupling ratios (e.g., 1:3, 2:6), and their correlations with maternal-fetal RR intervals.
Main Results:
- In the saline group, significant correlations were found between coupling ratios and RR intervals, and strong correlation between maternal and fetal RR intervals.
- In the VPA group, these significant correlations were absent.
- Maternal-fetal HR coupling patterns were altered in the VPA-exposed group compared to controls.
Conclusions:
- Specific maternal-fetal HR coupling patterns are crucial for normal fetal cardiac development.
- Prenatal VPA exposure may disrupt these vital cardiac interactions.
- Further research is needed to understand the implications of VPA-induced alterations in maternal-fetal HR coupling.
Abstract:
Prenatal uptake of valproic acid (VPA) was associated with increased risk of fetal cardiac anomalies and autism spectrum disorder (ASD), but uptake of VPA is considered the only effective treatment for epilepsy and other neurological disorders. Up until now, little is known about the effect of VPA on maternal - fetal heart rate (HR) coupling patterns; therefore, this study aims at studying such patterns in mice on embryonic day 15.5 (E15.5). At E12.5, 8 mothers were injected with VPA (VPA group) and another 8 mothers were injected with saline (control group). At E15.5, electrocardiogram (ECG) records of 15 minutes were collected from the 16 mothers and 25 fetuses. A maximum of 5-minutes and a minimum of 1-minute were selected from the ECG data for analysis. Mean RR intervals and coupling ratios and their occurrence percentages were calculated per 1minute. 1-minute analysis was done for periods with no arrhythmia and clear R peaks. The total number of 1-minute segments that were analyzed was 56 for the saline group and 54 for the VPA group. The correlation analysis between the 1:3 and 2:6 coupling ratios and RR intervals revealed that the ratios were significantly correlated in the saline group, whereas no significant correlations were observed in the VPA group. The results further revealed that fetal RR intervals are strongly correlated with maternal RR intervals in the saline group, but the same correlation is different in the VPA group. The presented results imply that maintaining certain coupling patterns are important for proper fetal cardiac development and maternal uptake of VPA may affect maternal-fetal HRs interactions.
