Serine racemase and D-serine transport in human placenta and evidence for a transplacental gradient for D-serine in humans

Objective To investigate the possible role of human placenta in providing D-serine to the developing fetus. Methods Expression of serine racemase in placenta was determined by reverse transcriptase polymerase chain reaction and northern analysis and confirmed by subsequent cloning. The transport of D-serine by human ATB⁰ was characterized by expressing the cloned cDNA transiently in mammalian cells using the vaccinia virus expression system. D-serine levels in maternal and fetal blood were measured by fluorescence high-performance liquid chromatography (HPLC) after derivatization of the amino acids with o-phthaldialdehyde and N-tertiary-butyloxycarbonyl-L-cysteine. Results mRNA for serine racemase was detected in placenta. ATB⁰ was capable of D-serine transport, and the transport process is obligatorily dependent on sodium (Na⁺) with a Na⁺:substrate stoichiometry of 1:1 and saturable with a Michaelis-Menten constant of 310 ± 30 μM. Furthermore, studies have shown that ATB⁰ is not expressed in the maternal-facing brush border membrane of human placental syncytiotrophoblast. The circulating concentration of D-serine in maternal serum is 5.8 ± 0.5 μM, and the corresponding value in the fetal serum is 14.6 ± 1.2 μM, indicating a two- to three-fold higher concentration of D-serine in the fetus than in the mother. Conclusion We speculate that D-serine is synthesized in human placenta by the racemization of L-serine and that ATB⁰, expressed on the basal membrane of the syncytiotrophoblast, mediates the efflux of D-serine into the fetal circulation in exchange for other amino acids in fetal blood.