Abstract
Metabolic disorders of the mother adversely affect early embryo development, causing changes in maternal metabolism and consequent alterations in the embryo environment in the uterus. The goal of this study was to analyse the biochemical profiles of embryonic fluids and blood plasma of rabbits with and without insulin-dependent diabetes mellitus (DT1), to identify metabolic changes associated with maternal diabetes mellitus in early pregnancy. Insulin-dependent diabetes was induced by alloxan treatment in female rabbits 10 days before mating. On day 6 post-coitum, plasma and blastocoel fluid (BF) were analysed by ultrahigh performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS) (Metabolon Inc. Durham, NC, USA). Metabolic datasets comprised a total of 284 and 597 compounds of known identity in BF and plasma, respectively. Diabetes mellitus had profound effects on maternal and embryonic metabolic profiles, with almost half of the metabolites changed. As predicted, we observed an increase in glucose and a decrease in 1,5-anhydroglucitol in diabetic plasma samples. In plasma, fructose, mannose, and sorbitol were elevated in the diabetic group, which may be a way of dealing with excess glucose. In BF, metabolites of the pentose metabolism were especially increased, indicating the need for ribose-based compounds relevant to DNA and RNA metabolism at this very early stage of embryo development. Other changes were more consistent between BF and plasma. Both displayed elevated acylcarnitines, body3-hydroxybutyrate, and multiple compounds within the branched chain amino acid metabolism pathway, suggesting that lipid beta-oxidation is occurring at elevated levels in the diabetic group. This study demonstrates that maternal and embryonic metabolism are closely related. Maternal diabetes mellitus profoundly alters the metabolic profile of the preimplantation embryo with changes in all subclasses of metabolites.
Highlights
During the preimplantation period, the development of the embryo is a well-regulated sequence of molecular events, starting with fertilisation of the oocyte and ending with implantation of the blastocyst in the uterine endometrium
Glucose metabolism predominates as the main energy source
We demonstrated that insulin-dependent diabetes mellitus alters the maternal metabolism in the way that there is a surplus of metabolites in the blood
Summary
The development of the embryo is a well-regulated sequence of molecular events, starting with fertilisation of the oocyte and ending with implantation of the blastocyst in the uterine endometrium. The preferred energy source for embryonic cellular metabolism changes [1,2]. In the early stages of embryonic development, aerobic glycolysis, known as the Krebs cycle, predominates, using pyruvate and lactate as the main sources of energy. Glucose uptake steadily increases, and glycolysis becomes increasingly more utilised for energy production [3]. Glucose metabolism predominates as the main energy source. This increase in glucose consumption in late-stage preimplantation embryos has been observed across several species, including mice, rats, humans, cows, sheep, rabbits and pigs [4]
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