Involuntary swimming exercise in pregnant rats disturbs ERK1/2 signaling in embryonic neurons through increased cortisol in the amniotic fluid.

Harmful maternal behaviors, such as drinking and smoking, negatively affect embryonic development. In contrast, regular maternal exercise is believed to be beneficial to the fetus. Although it is not surprising that voluntary physical activities are advantageous to fetal development, it remains unclear whether involuntary maternal exercise has similar effects. The constituents of the amniotic fluid (AF) inevitably reflect the maternal plasma. Therefore, it is speculated that exercise-induced changes in maternal plasma can influence fetal development through changes in AF composition. Therefore, we investigated the effect of AF on fetal neurodevelopment and changes in AF composition after involuntary swimming exercise (SE) in an animal model. We found that there was a severe reduction in the number of embryos implanted in the uterus of SE rats. Surprisingly, cortisol level (an inducible stress hormone) was significantly increased in AF from SE rats. In contrast, the growth factors NGF and VEGF were reduced in the AF from SE rats. In the cultured embryonic cortical neurons, the treatment of control (CTL) rat-derived AF significantly increased the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2)-mediated signaling that is essential for fetal neurodevelopment. However, the AF extracted from SE rats reversely suppressed the phosphorylation of ERK1/2-mediated signaling in cortical neurons compared to that in CTL rats. Indeed, the co-treatment with control AF and dexamethasone, a synthetic glucocorticoid, inhibited the phosphorylation of ERK1/2 in a dose-dependent manner. This finding suggests that the inhibition of ERK1/2 can be attributed to increased cortisol level in AF resulting from involuntary exercise. Therefore, involuntary maternal swimming increases cortisol level in AF, which ultimately hinders the ERK1/2 signaling pathway in embryonic neurons. These findings also suggest that involuntary maternal exercise can have undesirable effects on fetal neurodevelopment, which is potentially mediated by elevated AF cortisol level.