Diminished Maternal Tryptophan Leads to Sexually Dimorphic Differences in the Placenta-Brain Axis

Area of Science:

• Neuroscience
• Developmental Biology
• Nutritional Science

Background:

• Tryptophan (Trp) is essential for maternal and fetal health, serving as the serotonin (5-HT) precursor.
• Serotonin influences placenta function and fetal neurodevelopment.
• The placenta's mechanism for acquiring 5-HT (synthesis vs. transporter uptake) remains unclear.

Purpose of the Study:

• To investigate the effects of reduced maternal tryptophan on Trp, 5-HT, and 5-HIAA levels in dams and conceptuses.
• To determine if maternal Trp reduction impacts fetal brain and placental development, and if these effects differ between sexes.

Main Methods:

• Female mice were fed either a control (0.2% Trp) or reduced Trp (0.1%) diet for two weeks pre-breeding and during gestation.
• Conceptuses were collected at approximately 12.5 days post-coitus.
• Maternal blood, placenta, and fetal brain tissues were analyzed for Trp, 5-HT, and 5-HIAA levels, alongside transcriptomic analysis of placental and fetal brain tissues.

Main Results:

• Maternal Trp and 5-HT levels did not significantly decrease, but placental and fetal brain levels of both were reduced in conceptuses from dams on the reduced Trp diet.
• Female conceptuses showed greater susceptibility, with altered gene expression in placenta and fetal brain, including downregulation of transporters like Slc6a4 and Slc6a19.
• Reduced expression of these transporters correlated with lower Trp and 5-HT levels in the placenta of female conceptuses.

Conclusions:

• Subtle dietary reductions in tryptophan can profoundly affect conceptus development.
• These effects may lead to sex-specific vulnerabilities in fetal development.
• Findings suggest potential clinical implications for pregnant women, particularly concerning neurodevelopmental risks and sexual disparities.