Ellery S, et al. - Here, researchers examined whether expression of the enzymes required for creatine synthesis, and the creatine transporter, was altered in cases of placental insufficiency related to fetal growth restriction (FGR), and pre-eclampsia (PE). Expression of the two enzymes required for creatine synthesis was down-regulated in FGR placentae. These changes may affect creatine availability and dysregulate placental bioenergetics. Down-regulation of creatine synthesis and transport may be related to quiescence in a healthy pregnancy. Regulation of this ATP generating pathway was lacking in pathological pregnancies. This study proposes that the creatine kinase circuit plays an important role in placental bioenergetics.

Methods

• In this study, third trimester placentae were collected between 27-40 weeks’ gestation and included FGR (n=13), PE (n=21) and gestation-matched uncomplicated control (n=20), pregnancies.
• Total RNA was extracted and cDNA was generated from each sample.
• mRNA expression of the creatine transporter (SLC6A8) and synthesising enzymes arginine:glycine aminotransferase (AGAT) and guanidinoacetate methyltransferase (GAMT) was evaluated utilizing the Fluidigm BioMark HD system.
• Information was evaluated utilizing Wilcoxon rank-sum and Spearman correlation coefficient.

Results

• In all placentae, SLC6A8, AGAT and GAMT mRNA were detected.
• mRNA expression of AGAT (p
• Between 27-40 weeks in healthy pregnancies, mRNA expression of the creatine transporter and AGAT declined with advancing gestation (SLC6A8 p
• In any case, these connections were not seen in FGR or PE placentae.