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Mol Hum Reprod. 2019 Jul 19. pii: gaz039. doi: 10.1093/molehr/gaz039. [Epub ahead of print]

Placental Creatine Metabolism in Cases of Placental Insufficiency and Reduced Fetal Growth.

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The Ritchie Centre, Hudson Institute of Medical Research, and Department of Obstetrics & Gynaecology, Monash University.
Department of Physiology, Monash University, Clayton, Victoria; Department of Maternal-Fetal Medicine, Pregnancy Research Centre, Royal Women's Hospital and Department of Obstetrics and Gynaecology, University of Melbourne, Parkville, Victoria, Australia.
Institute for Physical Activity and Nutrition, School of Exercise Sciences, Deakin, Geelong, Australia.
Centre for Cellular and Molecular Biology, School of Life and Environmental Science, Deakin University, Burwood, Melbourne, Australia.
Dept of Obstetrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
School of Health & Biomedical Sciences, RMIT University, Melbourne, Australia.


Creatine is a metabolite involved in cellular energy homeostasis. In this study, we examined placental creatine content, and expression of the enzymes required for creatine synthesis, transport and the creatine kinase reaction, in pregnancies complicated by low birthweight. We studied first trimester chorionic villus biopsies (CVBs) of small for gestational age (SGA) and appropriately grown infants (AGA), along with third trimester placental samples from fetal growth restricted (FGR) and healthy gestation-matched controls. Placental creatine and creatine precursor (guanidinoacetate - GAA) levels were measured. Maternal and cord serum from control and FGR pregnancies were also analyzed for creatine concentration. mRNA expression of the creatine transporter (SLC6A8); synthesising enzymes arginine:glycine aminotransferase (GATM) and guanidinoacetate methyltransferase (GAMT); mitochondrial (mtCK) and cytosolic (BBCK) creatine kinases; and amino acid transporters (SLC7A1 & SLC7A2) was assessed in both CVBs and placental samples. Protein levels of AGAT (arginine:glycine aminotransferase), GAMT, mtCK and BBCK were also measured in placental samples. Key findings; total creatine content of the third trimester FGR placentae was 43% higher than controls. The increased creatine content of placental tissue was not reflected in maternal or fetal serum from FGR pregnancies. Tissue concentrations of GAA were lower in the third trimester FGR placentae compared to controls, with lower GATM and GAMT mRNA expression also observed. No differences in the mRNA expression of GATM, GAMT or SLC6A8 were observed between CVBs from SGA and AGA pregnancies. These results suggest placental creatine metabolism in FGR pregnancies is altered in late gestation. The relevance of these changes on placental bioenergetics should be the focus of future investigations.


intrauterine growth restriction; metabolism; phosphocreatine; placental bioenergetics; small for gestational age


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