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Open AccessArticle

The Effects of Early-Onset Pre-Eclampsia on Placental Creatine Metabolism in the Third Trimester

1
The Ritchie Centre, Hudson Institute of Medical Research, and Department of Obstetrics & Gynaecology, Monash University, Clayton 3168 Australia
2
Department of Pharmacology, Monash University, and Department of Obstetrics and Gynaecology, University of Melbourne, Parkville, Melbourne 3010, Australia
3
Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Geelong 3216, Australia
4
Centre for Cellular and Molecular Biology, School of Life and Environmental Science, Deakin University, Burwood, Melbourne 3125, Australia
5
School of Health & Biomedical Sciences, RMIT University, Melbourne 3082, Australia
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(3), 806; https://doi.org/10.3390/ijms21030806
Received: 10 December 2019 / Revised: 24 January 2020 / Accepted: 24 January 2020 / Published: 26 January 2020
(This article belongs to the Special Issue Molecular and Cellular Mechanisms of Preeclampsia)
Creatine is a metabolite important for cellular energy homeostasis as it provides spatio-temporal adenosine triphosphate (ATP) buffering for cells with fluctuating energy demands. Here, we examined whether placental creatine metabolism was altered in cases of early-onset pre-eclampsia (PE), a condition known to cause placental metabolic dysfunction. We studied third trimester human placentae collected between 27–40 weeks’ gestation from women with early-onset PE (n = 20) and gestation-matched normotensive control pregnancies (n = 20). Placental total creatine and creatine precursor guanidinoacetate (GAA) content were measured. mRNA expression of the creatine synthesizing enzymes arginine:glycine aminotransferase (GATM) and guanidinoacetate methyltransferase (GAMT), the creatine transporter (SLC6A8), and the creatine kinases (mitochondrial CKMT1A & cytosolic BBCK) was assessed. Placental protein levels of arginine:glycine aminotransferase (AGAT), GAMT, CKMT1A and BBCK were also determined. Key findings; total creatine content of PE placentae was 38% higher than controls (p < 0.01). mRNA expression of GATM (p < 0.001), GAMT (p < 0.001), SLC6A8 (p = 0.021) and BBCK (p < 0.001) was also elevated in PE placentae. No differences in GAA content, nor protein levels of AGAT, GAMT, BBCK or CKMT1A were observed between cohorts. Advancing gestation and birth weight were associated with a down-regulation in placental GATM mRNA expression, and a reduction in GAA content, in control placentae. These relationships were absent in PE cases. Our results suggest PE placentae may have an ongoing reliance on the creatine kinase circuit for maintenance of cellular energetics with increased total creatine content and transcriptional changes to creatine synthesizing enzymes and the creatine transporter. Understanding the functional consequences of these changes warrants further investigation. View Full-Text
Keywords: placental bioenergetics 1; phosphocreatine 2; metabolism 3; obstetrics 4 placental bioenergetics 1; phosphocreatine 2; metabolism 3; obstetrics 4
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Ellery, S.J.; Murthi, P.; Della Gatta, P.A.; May, A.K.; Davies-Tuck, M.L.; Kowalski, G.M.; Callahan, D.L.; Bruce, C.R.; Wallace, E.M.; Walker, D.W.; Dickinson, H.; Snow, R.J. The Effects of Early-Onset Pre-Eclampsia on Placental Creatine Metabolism in the Third Trimester. Int. J. Mol. Sci. 2020, 21, 806.

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