Candilera Vanessa, Bouchè Carlo, Schleef Jurgen, Pederiva Federica
a University of Trieste , Trieste , Italy .
b Department of Gynecology , and.
J Matern Fetal Neonatal Med. 2016;29(13):2104-8. doi: 10.3109/14767058.2015.1076387. Epub 2015 Aug 28.
Respiratory failure secondary to pulmonary hypoplasia is the main cause of death in congenital diaphragmatic hernia (CDH). Lung growth is regulated by growth factors (GFs), whose imbalances are reported in pathological conditions. We measured amniotic fluid levels of GFs, regulating lung development, in pregnancies with CDH and compared them with normal gestations.
Amniotic fluid was collected at amniocentesis and delivery from 4 women carrying fetuses with CDH and 12 with normal pregnancy. GFs were isolated and quantified. Same GFs were measured in lung biopsies collected during autopsy of three newborns dead of CDH.
Impairment expression of lung GFs in the amniotic fluid of CDH pregnancies in comparison with normal was found. Fibroblast growth factor 10 (FGF10), fibroblast growth factor 7, vascular endothelial growth factor and transforming growth factor β (TGFβ) were decreased at amniocentesis, while platelet-derived growth factor (PDGF) increased. While FGF10 and PDGF tended to normalize at delivery, epidermal growth factor increased and TGFβ was still decreased. Same GFs were similarly expressed in both lungs of babies dead of CDH.
Anomalies in lung GFs expression of embryos and fetuses with CDH can be detected by measuring their levels in the amniotic fluid during pregnancy. Further investigation would help to correlate prenatal expression of GFs and clinical outcome of babies with CDH after birth.
肺发育不全继发的呼吸衰竭是先天性膈疝(CDH)死亡的主要原因。肺生长受生长因子(GFs)调控,在病理状态下这些生长因子存在失衡情况。我们测定了患有CDH的孕妇羊水中调控肺发育的生长因子水平,并将其与正常妊娠进行比较。
从4例怀有患CDH胎儿的孕妇及12例正常妊娠孕妇的羊膜穿刺术及分娩时采集羊水。分离并定量生长因子。在3例死于CDH的新生儿尸检时采集的肺活检组织中测定相同的生长因子。
与正常情况相比,发现CDH妊娠孕妇羊水中肺生长因子表达受损。在羊膜穿刺术时,成纤维细胞生长因子10(FGF10)、成纤维细胞生长因子7、血管内皮生长因子和转化生长因子β(TGFβ)降低,而血小板衍生生长因子(PDGF)升高。虽然FGF10和PDGF在分娩时趋于正常化,但表皮生长因子升高,TGFβ仍降低。在死于CDH的婴儿的双肺中,相同的生长因子表达相似。
通过在孕期测量患有CDH的胚胎和胎儿羊水中生长因子的水平,可以检测到其肺生长因子表达异常。进一步的研究将有助于关联生长因子的产前表达与CDH患儿出生后的临床结局。