Placental hypoxia-regulating network in relation to birth weight and ponderal index: the ENVIRONAGE Birth Cohort Study

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.