Impact of Reduced Maternal Tryptophan on the Placenta-Brain Axis

Tryptophan is critical to mothers and their conceptuses, and this amino acid is the precursor to serotonin. Serotonin modulates placenta function and fetal neurodevelopment. It is not clear if the placenta directly synthesizes serotonin or uses the serotonin transporter (SERT/Sl6a4) to accrue this catecholamine from the dam. The hypothesis tested herein is that reduction in maternal tryptophan would lead to reductions in maternal tryptophan, serotonin, and 5-HIAA (a metabolite of serotonin) and corresponding reductions of these metabolites in placenta and fetal brain of female and male conceptuses. Female mice were placed on either a low tryptophan diet (1%) or control diet (2%).These diets were administered for two weeks prior to breeding (periconception period) until conceptuses were collected at approximately12.5 days post-coitus (dpc). While no reductions in maternal tryptophan and serotonin were observed, both metabolites were significantly reduced in in the placenta and fetal brain of male and female conceptuses (p < 0.05). Female conceptuses were particularly sensitive to reductions in maternal tryptophan with 652 and 29 transcripts being altered in the female placenta and fetal brain of low maternal tryptophan dams compared to control dams. Transcriptome changes, such as Sl6ca4 and Slc6a19 (transporter for tryptophan), in these organs were linked to reductions in tryptophan and serotonin amounts. Findings might have clinical relevance to pregnant women as they show even subtle reductions in one amino acid might profoundly influence offspring development and potential later risk for neurobehavioral disorders and the female conceptuses might be more vulnerable to in utero nutrient changes.