Williams Paula Juliet, Mistry Hiten D, Morgan Linda
Human Genetics, School of Molecular and Medical Sciences, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, United Kingdom.
Division of Women's Health, King's College London, Women's Health Academic Centre, KHP, St. Thomas' Hospital, London SE1 7EH, United Kingdom.
Pregnancy Hypertens. 2012 Apr;2(2):123-31. doi: 10.1016/j.preghy.2011.12.001. Epub 2012 Jan 4.
The transport of folate across the placenta involves a number of different receptors including folate receptor-alpha (FR-α), reduced folate carrier (RFC) and proton coupled folate transporter (PCFT). In addition there are a number of ATP-dependent transporters which have also recently been shown to be involved in folate transport; these include ABCB1, ABCC2 and BCRP (ABCG2). The aim of the current study was to characterise the placental mRNA and protein expression of these folate transporters throughout gestation and also to see if expression is altered in pre-eclampsia. Placental tissue was collected from women undergoing termination of pregnancy (TOP) and from women undergoing elective Caesarean section. To investigate mRNA expression quantitative real time PCR was used with gene specific oligonucleotide primers to FR-α, RFC, PCFT, ABCB1, ABCC2, BCRP and the reference gene YWHAZ. Protein expression was also characterised using immunohistochemistry of paraffin embedded placental tissue. Both protein and mRNA expression of all transporters examined decreased as the gestation progressed. Expression of FR-α and PCFT mRNA and protein were decreased in pre-eclampsia compared with normal term pregnancy. The higher levels of expression of FR-α, RFC, PCFT, ABCB1, ABCC2 and BCRP in early pregnancy indicate that these transporters may have an important role in the establishment and development of the placenta, with expression reducing in preparation for parturition. Reductions in FR-α and PCFT in pre-eclampsia may be a mechanism involved in the pathogenesis of pre-eclampsia by limiting placental folate uptake resulting in reduced levels of angiogenesis, cell proliferation and antioxidant protection.
叶酸通过胎盘的转运涉及多种不同的受体，包括叶酸受体-α（FR-α）、还原型叶酸载体（RFC）和质子偶联叶酸转运体（PCFT）。此外，还有一些ATP依赖性转运体，最近也被证明参与叶酸转运；这些包括ABCB1、ABCC2和BCRP（ABCG2）。本研究的目的是在整个妊娠期表征这些叶酸转运体在胎盘中的mRNA和蛋白质表达情况，并观察子痫前期时其表达是否发生改变。从接受终止妊娠（TOP）的妇女和接受择期剖宫产的妇女中收集胎盘组织。为了研究mRNA表达，使用基因特异性寡核苷酸引物对FR-α、RFC、PCFT、ABCB1、ABCC2、BCRP和参考基因YWHAZ进行定量实时PCR。还使用石蜡包埋的胎盘组织免疫组织化学对蛋白质表达进行表征。随着妊娠进展，所有检测转运体的蛋白质和mRNA表达均下降。与足月正常妊娠相比，子痫前期中FR-α和PCFT的mRNA和蛋白质表达降低。妊娠早期FR-α、RFC、PCFT、ABCB1、ABCC2和BCRP的较高表达水平表明，这些转运体可能在胎盘的建立和发育中起重要作用，随着分娩准备阶段的到来其表达降低。子痫前期中FR-α和PCFT的减少可能是子痫前期发病机制中的一种机制，通过限制胎盘叶酸摄取导致血管生成、细胞增殖和抗氧化保护水平降低。
