Amino acid mediated signalling in the first cell cycle of zygotes

Abstract

After fertilisation the developing embryo is exposed to substantial amounts of amino acids as it travels down the reproductive tract before implanting onto the uterine wall. Amino acids support development by regulating metabolism, cell volume and cellular pH. The addition of L-proline, L-glutamine (L-gln) and glycine to embryo culture medium improves development to the blastocyst stage and blastocyst hatching. Amino acids can also stimulate intracellular signalling pathways leading to cellular proliferation. The aim of this study was to investigate the correlation between the presence of amino acids in embryo culture medium and intracellular signalling pathways in the first cell cycle. This study investigated the impact of amino acids on phosphorylation of ERK1/2, AKT and rpS6 in all cell cycle stages of the mouse zygotes in vitro. Zygotes cultured in the presence of 1 mM L-gln had significantly decreased p-ERK1/2 and p-rpS6 expression in M-phase compared to freshly isolated zygotes. Whereas, the presence of all 20 amino acids did not alter expression of p-ERK1/2, p-AKT and p-rpS6 when compared to expression in freshly isolated zygotes. Understanding how amino acids stimulate intracellular signalling pathways provides insight into the tightly controlled culture environment during in vivo development. By understanding the effect of amino acids on the developing embryo, we can potentially develop a new generation of embryo culture media that incorporates amino acids for improved human IVF embryonic development.