Abstract
Heart rate is controlled by the activity of the autonomic nervous system: the sympathetic and parasympathetic nervous systems increase and suppress heart rate, respectively. To evaluate the activity of the autonomic nervous system, it is possible to determine heart rate variability using electrocardiography (ECG). During the fetal period, the heart and autonomic nerves develop in coordination; however, physiological changes, including autonomic nervous activities that occur during the fetal stage, remain largely unknown. Therefore, in this study, we measured ECG signals of mouse fetuses using our established method to evaluate the development of heart rate and autonomic nervous activity at different fetal developmental stages. We found that heart rate was significantly increased in fetal mice at embryonic day (E) 18.5 compared with that at E13.5, E15.5, and E17.5, indicating that fetal heart rate increases only at the stage immediately prior to birth. Interestingly, fetal parasympathetic nervous activity was reduced at E17.5 and E18.5 compared with that at E13.5, whereas fetal sympathetic nervous activity remained unchanged, at least from E13.5 to E18.5. These results indicate that parasympathetic activity rather than sympathetic activity affects fetal heart rate and that the decrease in parasympathetic activity toward the end of pregnancy could result in the observed increase in fetal heart rate.
Highlights
Heart rate is largely regulated by the autonomic nervous system, which includes two anatomical divisions: the sympathetic and parasympathetic nervous systems (Wehrwein et al, 2016)
We measured fetal ECG signals of a mouse model of autism spectrum disorder (ASD), which we established by administering valproic acid to pregnant mice, and assessed the autonomic function of these mice at both E15.5 and E18.5 using power spectrum analysis; we found that sympathetic nerve function was attenuated during the fetal period (Kasahara et al, 2020)
We showed that fetal heart rate increased at E18.5 compared with that at E15.5 in both saline- and valproic acid-treated mouse fetuses (Kasahara et al, 2020)
Summary
Heart rate is largely regulated by the autonomic nervous system, which includes two anatomical divisions: the sympathetic and parasympathetic nervous systems (Wehrwein et al, 2016). The sympathetic nervous system increases heart rate, whereas the parasympathetic nervous system suppresses it. The heart and autonomic nerves develop simultaneously; the physiological changes involving autonomic nervous activity that occur during the fetal stage have yet to be studied in detail. As described by Vegh et al (2016), at embryonic day (E) 8.0, the developing heart can be recognized as a primary heart tube; at this early stage, the autonomic nervous system has yet to be developed. At approximately E12.5, the migrating NCCs begin to play a role in the development of cardiac innervation and conduction. Catecholamine expression is essential for embryonic cardiac development in both the preinnervation and postinnervation phases, and fetuses are completely dependent on noradrenalin from E9.5 to E13.5 (Vegh et al, 2016). To study the coordinated development of the heart and autonomic nervous system in fetal mice based on physiological characteristics, it is necessary to study fetal development after E13.5
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