Effect of folic acid diet on the behavior of female mice and ultrasonic vocalization of their F1 offspring

Folic acid (FA) is an essential B vitamin that plays a pivotal in various physiological processes, including neural tube defects, brain functions, neurotransmitter synthesis, and cognition. Earlier studies have suggested FA's role during pregnancy and the development of newborns; however, the broader impact of FA diet on maternal and offspring health remains unclear. Herein, the effects of FA on the behavior of female mice and ultrasonic vocalizations (USVs) of their F1 offspring were evaluated. Briefly, mice were placed into control, 2.3 mg FA, and 8 mg FA. Folic acid was supplemented in female mice at concentrations of 2.3 mg/kg and 8 mg/kg for 6 weeks. Afterward, female mice behavior was assessed via open field test, novel object recognition test, and gait analysis as well as acetylcholinesterase activity were performed. Further, USVs of their F1 offspring on postnatal days (PND) 7, 9, 11, and 13 were measured. Results showed that the FA supplementation in female mice reduced locomotor activity, impaired memory, increased anxiety-like behavior, and altered gait (walking pattern). Meanwhile, alterations were also observed in the level of acetylcholinesterase activity, while the change did not attain statistical significance. On the other hand, F1 offspring born from FA 8 mg supplemented mice showed substantial changes in USVs like extended call durations, increased frequencies, and higher amplitudes compared to FA 2.3 mg supplemented female mice offspring. Also, F1 offspring of FA 2.3 mg supplemented mice showed higher vocalizations pattern compared to control F1 offspring. Such study is useful to understand the impact of FA during pregnancy and its potential transgenerational effects, and helpful to understand maternal and offspring health.