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Characterization and Regulation of Monocarboxylate Cotransporters Slc16a7 and Slc16a3 in Preimplantation Mouse Embryos¹

School of Biomedical Sciences, University of Queensland, Brisbane 4072, Queensland, Australia

ABSTRACT

Concurrent with compaction, preimplantation mouse embryos switch from the high pyruvate consumption that prevailed during cleavage stages to glucose consumption against a constant background of pyruvate uptake. However, zygotes exposed to and subsequently deprived of glucose can form blastocysts by increasing pyruvate uptake. This metabolic switch requires cleavage-stage exposure to glucose and is one aspect of metabolic differentiation that normally occurs in vivo. Monocarboxylates, such as pyruvate and lactate, are transported across membranes via the SLC16 family of H⁺-monocarboxylate cotransporter (MCT) proteins. Thus, the increase in pyruvate uptake in embryos developing without glucose must involve changes in activity and localization of MCT. In mouse embryos, continued expression of Slc16a1 (MCT1) requires glucose supply. Messenger RNA for Slc17a7 (MCT2) and Slc16a3 (MCT4) has been detected in mouse preimplantation embryos; however, protein function, localization, and regulation of expression at the basis of these net pyruvate uptake changes remain unclear. The expression and localization of SLC16A7 and SLC16A3 have therefore been examined to clarify their respective roles in embryos derived from the reproductive tract and cultured under varied conditions. SLC16A3 appears localized to the plasma membrane until the morula stage and also maintains a nuclear distribution throughout preimplantation development. However, continued Slc16a3 mRNA expression is dependent on prior exposure to glucose. SLC16A7 localizes to apical cortical regions with punctate, vesicular expression throughout blastomeres, partially colocalizing in peroxisomes with peroxisomal catalase (CAT). In contrast to SLC16A3 and SLC16A1, SLC16A7 and CAT demonstrate upregulation in the absence of glucose. These striking differences between the two isoforms in expression localization and regulation suggest unique roles for each in monocarboxylate transport and pH regulation during preimplantation development, and implicate peroxisomal SLC16A7 as an important redox regulator in the absence of glucose.

conceptus, early development, environment, monocarboxylate transporters, nutrient

¹Supported by National Health and Medical Research Council of Australia project grant 210194 to M.P. and P.L.K. and National Institute of Child Health and Human Development National Cooperative Program on Female Health and Egg Quality cooperative agreement U01 HD044644. S.J. was supported by a University of Queensland Graduate School Joint Research Scholarship.

Correspondence: ²FAX: 617 3365 1766; e-mail: p.kaye{at}uq.edu.au