21 Trainee Abstract Award: Long-term effects of reduced docosahexaenoic acid placental transfer on offspring neurobehavioral outcomes in mice

Abstract Abstract: Introduction Docosahexaenoic acid (DHA) is critical for fetal brain development. Inadequate supply during the perinatal period has been associated with an impaired neurological function in children. DHA is transported from the mother to the fetus via the placenta by the Major Facilitator Superfamily Domain Containing 2a (MFSD2a) transporter. Objective We hypothesize that placenta-specific knockdown (KD) of MFSD2a in mice causes neurobehavioral changes in adult offspring. Methods We generated placenta-specific KD of MFSD2a using a mouse model of trophectoderm lentivirus transfection and embryo transfer. Neurobehavioral functions such as cognition, memory, motor skills and anxiety-like behaviors as well as social interaction were tested at 3 months of age in male and female mice from placental MFSD2a KD and non-coding transfection (SCR) pregnancies using Open field, Double H maze, Three-Chamber Sociability and Rotarod test. Results Adult mice from pregnancies with placental MFSD2a KD demonstrated a significant increase of anxiety-like behavior (n = 34 SCR and n = 39 MFSD2a KD, p-value<0.0001) and an impaired mobility (n = 41 SCR, n = 46 MFSD2a KD, p-value<0.001) predominantly in females. No significant differences were observed in memory or social behavior. Conclusion Our results suggest that placental DHA transfer by MFSD2a during pregnancy is critical for long-term neurodevelopment. (Supported by NIH HD104644)