de Alwis Natasha, Beard Sally, Binder Natalie K, Pritchard Natasha, Kaitu'u-Lino Tu'uhevaha J, Walker Susan P, Stock Owen, Groom Katie, Petersen Scott, Henry Amanda, Said Joanne M, Seeho Sean, Kane Stefan C, Tong Stephen, Hui Lisa, Hannan Natalie J
Therapeutics Discovery and Vascular Function in Pregnancy Group, Mercy Hospital for Women, Heidelberg, VIC 3084, Australia.
Mercy Perinatal, Mercy Hospital for Women, Heidelberg, VIC 3084, Australia.
Antioxidants (Basel). 2022 Aug 27;11(9):1677. doi: 10.3390/antiox11091677.
Previously, we identified elevated transcripts for the gene Oleoyl-ACP Hydrolase () in the maternal circulation of pregnancies complicated by preterm fetal growth restriction. As placental dysfunction is central to the pathogenesis of both fetal growth restriction and preeclampsia, we aimed to investigate OLAH levels and function in the human placenta. We assessed mRNA expression (qPCR) throughout pregnancy, finding placental expression increased as gestation progressed. mRNA and protein levels (Western blot) were elevated in placental tissue from cases of preterm preeclampsia, while OLAH protein levels in placenta from growth-restricted pregnancies were comparatively reduced in the preeclamptic cohort. expression was also elevated in placental explant tissue, but not isolated primary cytotrophoblast cultured under hypoxic conditions (as models of placental dysfunction). Further, we discovered that silencing cytotrophoblast reduced the expression of pro- and anti-apoptosis genes, and , placental growth gene, , and oxidative stress gene, . Collectively, these findings suggest OLAH could play a role in placental dysfunction and may be a therapeutic target for mitigating diseases associated with this vital organ. Further research is required to establish the role of OLAH in the placenta, and whether these changes may be a maternal adaptation or consequence of disease.
此前，我们在合并早产胎儿生长受限的妊娠母体循环中发现基因油酰-ACP水解酶（）的转录本水平升高。由于胎盘功能障碍是胎儿生长受限和先兆子痫发病机制的核心，我们旨在研究人胎盘中OLAH的水平和功能。我们评估了整个孕期的mRNA表达（qPCR），发现胎盘表达随孕周增加而升高。早产先兆子痫病例的胎盘组织中mRNA和蛋白水平（蛋白质印迹法）升高，而在先兆子痫队列中，生长受限妊娠胎盘的OLAH蛋白水平相对降低。在胎盘外植体组织中表达也升高，但在缺氧条件下培养的分离原代细胞滋养层（作为胎盘功能障碍模型）中未升高。此外，我们发现沉默细胞滋养层中的可降低促凋亡和抗凋亡基因、胎盘生长基因以及氧化应激基因的表达。总体而言，这些发现表明OLAH可能在胎盘功能障碍中起作用，并且可能是减轻与这个重要器官相关疾病的治疗靶点。需要进一步研究来确定OLAH在胎盘中的作用，以及这些变化是母体的适应性反应还是疾病的后果。
