de Alwis Natasha, Beard Sally, Baird Lydia, Binder Natalie K, Pritchard Natasha, Tong Stephen, Kaitu'u-Lino Tu'uhevaha J, Hui Lisa, Hannan Natalie J
Department of Obstetrics, Gynaecology and Newborn Health, The University of Melbourne and Mercy Hospital for Women, 163 Studley Rd, Heidelberg, Melbourne, VIC, 3084, Australia.
Northern Health, Epping, Melbourne, VIC, 3076, Australia.
Sci Rep. 2025 Apr 3;15(1):11381. doi: 10.1038/s41598-025-94498-w.
The placenta plays an essential role facilitating nutrient, gas and waste exchange between the maternal and fetal systems for optimal fetal growth. When placental development is impaired and the placenta dysfunctional, serious pregnancy complications such as fetal growth restriction and preeclampsia may arise. Previously, phosphoglucomutase-5 (PGM5) transcripts were found to be highly elevated in the blood of patients whose pregnancies were complicated by fetal growth restriction and preeclampsia. As both conditions feature placental insufficiency, here we aimed to characterise PGM5 levels in the healthy and dysfunctional placenta. PGM5 expression was detectable in all placental samples across gestation, in cases of preterm preeclampsia, fetal growth restriction and controls. PGM5 mRNA expression was significantly downregulated in the pathological placentas compared to controls, but PGM5 protein production was not dysregulated. Isolated cytotrophoblast and placental explant tissue exposed to hypoxia (modelling placental dysfunction) demonstrated significantly increased PGM5 expression, but again did not change protein levels. Silencing PGM5 expression under hypoxic conditions in primary cytotrophoblast did not alter anti-angiogenic sFLT-1 secretion but increased expression of multiple genes associated with cell growth, apoptosis and oxidative stress, whilst also increasing cell viability. Expression of PGM5 in all placental samples assessed suggests that PGM5 has functions in the placenta. However, further investigation could be performed to explore the discrepancies in protein and mRNA expression, as well as the precise function of PGM5 in the placenta, and whether altered PGM5 levels may be important for placental development.
胎盘在促进母体和胎儿系统之间的营养、气体和废物交换以实现胎儿最佳生长方面发挥着至关重要的作用。当胎盘发育受损且功能失调时,可能会出现诸如胎儿生长受限和先兆子痫等严重的妊娠并发症。此前,在妊娠合并胎儿生长受限和先兆子痫的患者血液中发现磷酸葡萄糖变位酶-5(PGM5)转录物高度升高。由于这两种情况都具有胎盘功能不全的特征,因此我们旨在表征健康胎盘和功能失调胎盘中的PGM5水平。在早产先兆子痫、胎儿生长受限病例及对照组的整个妊娠期所有胎盘样本中均可检测到PGM5表达。与对照组相比,病理胎盘组织中的PGM5 mRNA表达显著下调,但PGM5蛋白产生未出现失调。分离的细胞滋养层细胞和胎盘外植体组织暴露于低氧环境(模拟胎盘功能障碍)时,PGM5表达显著增加,但蛋白水平同样未发生变化。在原代细胞滋养层细胞的低氧条件下沉默PGM5表达,并未改变抗血管生成的可溶性fms样酪氨酸激酶-1(sFLT-1)分泌,但增加了与细胞生长、凋亡和氧化应激相关的多个基因的表达,同时也提高了细胞活力。在所评估的所有胎盘样本中PGM5的表达表明PGM5在胎盘中具有功能。然而,可进一步开展研究以探讨蛋白和mRNA表达的差异,以及PGM5在胎盘中的确切功能,以及PGM5水平的改变对胎盘发育是否可能具有重要意义。