Ellery Stacey J, Murthi Padma, Davies-Tuck Miranda L, Della Gatta Paul A, May Anthony K, Kowalski Greg M, Callahan Damien L, Bruce Clinton R, Alers Nicole O, Miller Suzanne L, Erwich Jan Jaap H M, Wallace Euan M, Walker David W, Dickinson Hayley, Snow Rod J
The Ritchie Centre, Hudson Institute of Medical Research, and Department of Obstetrics & Gynaecology, Monash University, Melbourne, Australia.
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.
Mol Hum Reprod. 2019 Aug 1;25(8):495-505. doi: 10.1093/molehr/gaz039.
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); synthesizing 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.
肌酸是一种参与细胞能量稳态的代谢物。在本研究中，我们检测了低出生体重妊娠中胎盘肌酸含量，以及肌酸合成、转运和肌酸激酶反应所需酶的表达。我们研究了小于胎龄儿（SGA）和发育正常婴儿（AGA）孕早期的绒毛膜绒毛活检样本（CVB），以及胎儿生长受限（FGR）和健康妊娠匹配对照的孕晚期胎盘样本。测量了胎盘肌酸和肌酸前体（胍基乙酸 - GAA）水平。还分析了对照和FGR妊娠的母血和脐血血清中的肌酸浓度。在CVB和胎盘样本中评估了肌酸转运体（SLC6A8）、合成酶精氨酸：甘氨酸转氨酶（GATM）和胍基乙酸甲基转移酶（GAMT）、线粒体（mtCK）和胞质（BBCK）肌酸激酶以及氨基酸转运体（SLC7A1和SLC7A2）的mRNA表达。还测量了胎盘样本中AGAT（精氨酸：甘氨酸转氨酶）、GAMT、mtCK和BBCK的蛋白水平。主要发现：孕晚期FGR胎盘的总肌酸含量比对照组高43%。胎盘组织中肌酸含量的增加并未反映在FGR妊娠的母血或胎儿血清中。与对照组相比，孕晚期FGR胎盘的GAA组织浓度较低，同时也观察到GATM和GAMT mRNA表达较低。SGA和AGA妊娠的CVB之间未观察到GATM、GAMT或SLC6A8的mRNA表达差异。这些结果表明，FGR妊娠中胎盘肌酸代谢在妊娠晚期发生了改变。这些变化对胎盘生物能量学的相关性应是未来研究的重点。
