Center for Environmental Sciences, Molecular & Environmental Epidemiology, Hasselt University, Agoralaan Building D, 3590, Diepenbeek, Belgium.
Department of Obstetrics, East-Limburg Hospital, 3600, Genk, Belgium.
J Transl Med. 2018 Jan 10;16(1):2. doi: 10.1186/s12967-017-1375-5.
HIF1α, miR-210 and its downstream targets ISCU, COX-10, RAD52 and PTEN are all part of the placental hypoxia-responsive network. Tight regulation of this network is required to prevent development of maternal-fetal complications such as fetal growth restriction. HIF1α expression is increased in preeclamptic placentae, but little is known about its association with birth weight in normal pregnancies.
We measured placental levels of HIF1α, miR-20a, miR-210, ISCU, COX-10, RAD52 and PTEN in 206 mother-newborn pairs of the ENVIRONAGE birth cohort.
Placental HIF1α gene expression was inversely associated with the ponderal index (PI): for a doubling in placental HIF1α expression, PI decreased by 6.7% (95% confidence interval [CI] 1.3 to 12.0%, p = 0.01). Placental RAD52 expression also displayed an inverse association with PI, a doubling in gene expression was associated with a 6.2% (CI 0.2 to 12.1% p = 0.04) decrease in PI. As for birth weight, we observed a significant association with placental miR-20a expression only in boys, where a doubling in miR-20a expression is associated with a 54.2 g (CI 0.6 to 108 g, p = 0.05) increase in birth weight.
The decrease in fetal growth associated with expression of hypoxia-network members HIF1a, RAD52 and miR-20a indicates that this network is important in potential intrauterine insults.
HIF1α、miR-210 及其下游靶标 ISCU、COX-10、RAD52 和 PTEN 均属于胎盘缺氧反应网络的一部分。为防止胎儿生长受限等母婴并发症的发生，需要对该网络进行严格调控。子痫前期胎盘组织中 HIF1α 的表达增加，但目前尚不清楚其与正常妊娠中出生体重的关系。
我们在 ENVIRONAGE 出生队列的 206 对母婴中测量了胎盘组织中 HIF1α、miR-20a、miR-210、ISCU、COX-10、RAD52 和 PTEN 的水平。
胎盘 HIF1α 基因表达与体重指数（PI）呈负相关：胎盘 HIF1α 表达增加一倍，PI 降低 6.7%（95%置信区间 [CI] 1.3 至 12.0%，p=0.01）。胎盘 RAD52 表达也与 PI 呈负相关，基因表达增加一倍，PI 降低 6.2%（CI 0.2 至 12.1%，p=0.04）。至于出生体重，我们仅在男孩中观察到与胎盘 miR-20a 表达的显著相关性，miR-20a 表达增加一倍与出生体重增加 54.2g（CI 0.6 至 108g，p=0.05）相关。
与缺氧网络成员 HIF1a、RAD52 和 miR-20a 表达相关的胎儿生长减少表明该网络在潜在的宫内损伤中很重要。
