Serine Racemase and D-Serine Transport in Human Placenta and Evidence for a Transplacental Gradient for D-Serine in Humans

Abstract

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 adids 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 and 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 recemization of L-serine and that ATB⁰, expressed on the basal membrane of the syncytiotrophoblast, mediates the efflux of D-serine into fetal circulation in exchange for other amino acids in fetal blood.

Keywords

Trophoblast amino acid transport transplacental development

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