Maternal enzyme masks the phenotype of mouse embryos lacking dihydrolipoamide dehydrogenase

Abstract

During early embryogenesis, the phenotype reflecting the embryonic genotype emerges only as maternal proteins are replaced by embryonically encoded forms, a process known as the maternal-to-embryonic transition (MET). Little is understood about MET for most proteins. This study investigates how complete deficiency of the murine dihydrolipoamide dehydrogenase gene (Dld), a gene that encodes an enzyme of mitochondrial energy metabolism, affects the phenotype of the early embryo and how the MET of the DLD protein affects the phenotype. Dld-deficient (−/−) embryos were found to develop similarly to wild-type (+/+) or heterozygous (+/−) embryos throughout the preimplantation period. These three genotypic classes also have comparable rates of glucose uptake (4.9–5.0 pmoles/embryo/h) and lactate production (0.97–1.0 pmoles/embryo/h). Dld-deficient embryos at the end of the preimplantation stage have 44% of DLD enzyme present in oocytes, a proportion similar to that found in +/+ or +/− embryos. This study demonstrates that Dld-deficient preimplantation embryos are phenotypically normal, as the MET for the DLD enzyme is only partially complete by the end of the preimplantation period. These findings have implications for phenotype- or enzyme-based approaches to identify mutations in Dld and other genes that encode proteins with similar MET kinetic profiles.

Effect of Exposure to Seminal Plasma Through Natural Mating in Cattle on Conceptus Length and Gene Expression

“…DLD and PTGS2 relative expression was higher in long filamentous or tubular embryos recovered from mated heifers than unmated heifers. DLD encodes for the mitochondrial dihydrolipoamide dehydrogenase, a member of the class-I pyridine nucleotidedisulfide oxidoreductase family crucial for embryo energy production (Leese, 1991;Johnson et al, 2009). Moreover, this enzyme seems to be essential for preimplantation embryos as DLD knockout mice embryos are unable to undergo gastrulation (Johnson et al, 1997).…”

Sorbin and SH3 Domain‐Containing Protein 2 Is Released From Infarcted Heart in the Very Early Phase: Proteomic Analysis of Cardiac Tissues From Patients

“…Dihydrolipoyl dehydrogenase is also an essential element of the pyruvate dehydrogenase complex (E3 component) and other mitochondrial multienzyme complexes, such as alpha‐ketoglutarate dehydrogenase, branched‐chain alpha‐ketoacid dehydrogenase, and the glycine cleavage system. 42–43 Dihydrolipoyl dehydrogenase generates ATP from major energy substrates. 3‐Hydroxyisobutyrate dehydrogenase catalyzes degradation of the glucogenic amino acid valine to produce the metabolic intermediate succinyl‐CoA 44–45 and is involved in satisfying increasing energy demand.…”

Human and mouse embryonic development, metabolism and gene expression are altered by an ammonium gradient in vitro

“…Both pyruvate dehydrogenase phosphatase isoenzyme 2 and 6-phosphofructokinase/ fructose-2,6-bisphosphatase are key enzymes regulating pyruvate metabolism and glycolysis (Roche et al 2001, Rider et al 2004 and their potential down-regulation could conceivably impact metabolic flux. However, the enzyme dihydrolipoamide dehydrogenase is present throughout the preimplantation period from maternal sources synthesized during oocyte maturation, and consequently changes in gene expression at the blastocyst stage may well only have effects after implantation (Johnson et al 2009). Furthermore, in the presence of ammonium, there was decreased expression of the glucose transporter SLC2A1 (GLUT1).…”