Abstract
BackgroundPregnancy induces adaptations in maternal metabolism to meet the increased need for nutrients by the placenta and fetus. Creatine is an important intracellular metabolite obtained from the diet and also synthesised endogenously. Experimental evidence suggests that the fetus relies on a maternal supply of creatine for much of gestation. However, the impact of pregnancy on maternal creatine homeostasis is unclear. We hypothesise that alteration of maternal creatine homeostasis occurs during pregnancy to ensure adequate levels of this essential substrate are available for maternal tissues, the placenta and fetus. This study aimed to describe maternal creatine homeostasis from mid to late gestation in the precocial spiny mouse.MethodsPlasma creatine concentration and urinary excretion were measured from mid to late gestation in pregnant (n = 8) and age-matched virgin female spiny mice (n = 6). At term, body composition and organ weights were assessed and tissue total creatine content determined. mRNA expression of the creatine synthesising enzymes arginine:glycine amidinotransferase (AGAT) and guanidinoacetate methyltransferase (GAMT), and the creatine transporter (CrT1) were assessed by RT-qPCR. Protein expression of AGAT and GAMT was also assessed by western blot analysis.ResultsPlasma creatine and renal creatine excretion decreased significantly from mid to late gestation (P < 0.001, P < 0.05, respectively). Pregnancy resulted in increased lean tissue (P < 0.01), kidney (P < 0.01), liver (P < 0.01) and heart (P < 0.05) mass at term. CrT1 expression was increased in the heart (P < 0.05) and skeletal muscle (P < 0.05) at term compared to non-pregnant tissues, and creatine content of the heart (P < 0.05) and kidney (P < 0.001) were also increased at this time. CrT1 mRNA expression was down-regulated in the liver (<0.01) and brain (<0.01) of pregnant spiny mice at term. Renal AGAT mRNA (P < 0.01) and protein (P < 0.05) expression were both significantly up-regulated at term, with decreased expression of AGAT mRNA (<0.01) and GAMT protein (<0.05) observed in the term pregnant heart. Brain AGAT (<0.01) and GAMT (<0.001) mRNA expression were also decreased at term.ConclusionChange of maternal creatine status (increased creatine synthesis and reduced creatine excretion) may be a necessary adjustment of maternal physiology to pregnancy to meet the metabolic demands of maternal tissues, the placenta and developing fetus.
Highlights
Pregnancy induces adaptations in maternal metabolism to meet the increased need for nutrients by the placenta and fetus
While creatine is thought to be an essential metabolite for the growing fetus [9,10], whether maternal creatine metabolism is altered in pregnancy has received little attention
Creatine is readily obtained from a diet of animal products and is synthesised by the body through the production of guanidinoacetate (GAA), catalysed by the enzyme arginine:glycine aminotransferase (AGAT) predominately in the kidney, followed by the methylation of GAA, mainly in the liver, to produce creatine [12]
Summary
Pregnancy induces adaptations in maternal metabolism to meet the increased need for nutrients by the placenta and fetus. These changes include shifts into anabolic metabolism during the first and second trimesters [2] This allows for fat accumulation in the mother, to be used as an energy source for maternal tissues during the third trimester, when a switch to catabolic metabolism takes place to ensure an enhanced nutrient supply to the growing fetus [2,3,4,5,6]. These adaptations to meet fetal requirements for growth encompass large changes in maternal glucose, carbohydrate, amino acid, lipid and fatty acid metabolism [2,7]. Once synthesised or absorbed creatine is moved into tissues by the creatine transporter-1 protein (CrT1) [13] where ~75% is phosphorylated and used as a source of phosphate for the regeneration of ATP [14]
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