Tan Choo Xiang, Yeoh Hannah Xin Yi, Tazilan Nur Aqilah Amani Mohamad, Tan Jonathan Wei De, Alfian Nurwardah, Zakaria Haliza, Azhar Shah Shamsul, Rahman Rahana Abd, Wong Yin Ping, Tan Geok Chin
Department of Pathology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia.
Department of Obstetrics and Gynaecology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia.
Diagnostics (Basel). 2025 Jul 22;15(15):1843. doi: 10.3390/diagnostics15151843.
: The worldwide prevalence of FGR is about 13% and can lead to various adverse perinatal outcomes, including preterm birth, stillbirth, and neonatal mortality. Hypoxia-Inducible Factor-1 (HIF-1) is an important regulator of oxygen homeostasis in humans and is crucial for placental development. The aim of this study is to determine the pattern of HIF-1A expression in placenta, and to correlate its association with preeclampsia, fetal growth restriction and adverse perinatal outcomes. : This study comprised a total of 158 cases with 42 cases of mother having babies with fetal growth restriction (FGR), 39 cases of mother with preeclampsia (PE), 35 cases of mother with preeclampsia and fetal growth restriction and 42 controls. The expression of HIF-1A was evaluated in various placental cell types, including cytotrophoblasts, syncytiotrophoblasts, fetal endothelial cells, maternal endothelial cells, and decidual cells. : The expression of HIF-1A in placental decidual cells of mother with FGR (21/42, 50%, < 0.0001), PE (25/39, 64.1%, < 0.0001) and PE with FGR (12/35, 34.3%, < 0.0001) were significantly increased compared to controls (1/42). Intriguingly, HIF-1A expression was significantly reduced in the placental cytotrophoblasts and syncytiotrophoblasts of mother with PE and FGR (2/35, 5.7%) compared to PE alone (11/39, 28.2%) ( = 0.0142). : We found that increased HIF-1A expression in the nuclei of decidual cells was observed in the mothers of babies with FGR, both with and without PE. While HIF-1A expression in the cytotrophoblasts and syncytiotrophoblasts was significantly reduced between mothers with PE and mothers with PE and FGR. This suggests HIF-1A expression might play a role in the pathogenesis of FGR.
胎儿生长受限(FGR)在全球的患病率约为13%,可导致各种不良围产期结局,包括早产、死产和新生儿死亡。缺氧诱导因子-1(HIF-1)是人体氧稳态的重要调节因子,对胎盘发育至关重要。本研究的目的是确定胎盘组织中HIF-1A的表达模式,并将其与子痫前期、胎儿生长受限及不良围产期结局的相关性进行关联分析。本研究共纳入158例病例,其中42例母亲所生婴儿患有胎儿生长受限(FGR),39例母亲患有子痫前期(PE),35例母亲患有子痫前期合并胎儿生长受限,42例为对照组。对包括细胞滋养层细胞、合体滋养层细胞、胎儿内皮细胞、母体内皮细胞和蜕膜细胞在内的各种胎盘细胞类型中HIF-1A的表达进行评估。与对照组(1/42)相比,FGR母亲(21/42,50%,P<0.0001)、PE母亲(25/39,64.1%,P<0.0001)和PE合并FGR母亲(12/35,34.3%,P<0.0001)胎盘蜕膜细胞中HIF-1A的表达显著增加。有趣的是,与单纯PE母亲(11/39,28.2%)相比,PE合并FGR母亲胎盘的细胞滋养层细胞和合体滋养层细胞中HIF-1A表达显著降低(2/35,5.7%)(P=0.0142)。我们发现,无论是否合并PE,FGR婴儿母亲的蜕膜细胞核中HIF-1A表达均增加。而在PE母亲与PE合并FGR母亲之间,细胞滋养层细胞和合体滋养层细胞中的HIF-1A表达显著降低。这表明HIF-1A表达可能在FGR的发病机制中起作用。