Gamma-aminobutyric acid (GABA) can affect physiological processes in preimplantation embryos via GABAA and GABAB receptors

PurposeSeveral widely used substances (e.g., some therapeutics or food supplements) can act on gamma-aminobutyric acid (GABA) receptors, and we investigated whether the activation of these receptors could affect the preimplantation embryo. MethodsTranscripts of all GABA receptor subunits and selected proteins were examined using quantitative RT-PCR and immunohistochemistry. To analyze the effects of receptor activation, in vitro culture of mouse preimplantation embryos with natural and synthetic GABA receptor ligands was used. ResultsWe detected nine GABA receptor transcripts in mouse blastocysts and 14 GABA receptor transcripts in ovulated oocytes. The results of this study indicate that ionotropic GABA(A) receptors can be formed from & alpha;5, & beta;3, and & gamma;3 (or & delta;, & pi;) subunits, GABA(A-& rho;) receptors can be formed from & rho;2 subunits and metabotropic GABA receptors can be formed from GABA(B1b) and GABA(B2) subunits in mouse blastocysts. Supplementing the culture medium with GABA at concentrations of 2-10 mM or with specific GABA(A) and GABA(B) receptor agonists (at concentrations of 10-100 & mu;M) significantly increased the proportion of dead cells in blastocysts. The GABA-induced effects were prevented by pretreatment of embryos with GABA(A) and GABA(B) receptor antagonists. ConclusionThe results of this study indicate that GABA and synthetic GABA receptor ligands can negatively affect preimplantation embryos via GABA(A) and GABA(B) receptors.

Automated summary

This study found that the activation of GABA receptors by certain substances can have negative effects on preimplantation embryos. The presence of various GABA receptor subunits was detected in mouse blastocysts and ovulated oocytes. Adding GABA or specific GABA receptor agonists to the culture medium significantly increased cell death in blastocysts, and this effect was prevented by GABA receptor antagonists.