Abnormalities of placental development and function are associated with the different fetal growth patterns of hypoplastic left heart syndrome and transposition of the great arteries
Abnormalities of placental development and function are associated with the different fetal growth patterns of hypoplastic left heart syndrome and transposition of the great arteries
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DOI：
10.1016/j.placenta.2020.09.007
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发表时间：
2020-11-01
期刊：
影响因子：
3.8
通讯作者：
Jones, Helen N.
中科院分区：
文献类型：
--
作者：
Courtney, Jennifer;Troja, Weston;Jones, Helen N.
背景：出生体重是先天性心脏病（CHD）手术结果的重要预测因素。左心发育不良综合征（HLHS）是已知胎儿生长受限和胎盘异常的紫绀型冠心病。大动脉转位（TGA）是胎儿生长正常的紫绀型冠心病。胎盘在这些诊断中的比较可能提供对CHD胎儿生长异常的见解。方法：对大动脉转位（TGA）相关胎盘的临床资料和组织学进行分析，包括大体病理学、形态学、成熟度和血管分布，并与对照组和先前分析的HLHS胎盘[1]进行比较。从HLHS、TGA和对照胎盘中分离RNA，利用Illumina HiSeq进行测序。使用AltAnalyze进行转录组分析。利用免疫组织化学方法评估三组胎盘营养转运蛋白的表达。结果：与对照组相比，TGA患者的胎盘重量减轻，绒毛血管减少，薄壁终末绒毛未成熟，反映了我们之前从HLHS胎盘中获得的数据。然而，与HLHS队列相比，TGA病例的出生体重并没有减少；与对照组相比，TGA病例的胎盘重量比显著增加，而HLHS病例的胎盘重量比则没有显著增加。转录组学和组织学分析表明，HLHS胎盘的细胞活性和营养转运能力降低，而TGA胎盘的细胞活性和营养转运能力没有降低，TGA胎盘似乎增加/维持了这些机制。结论：尽管HLHAs和TGA在胎盘中存在常见的血管紊乱，但这些并不能解释这些冠心病亚型之间常见的出生体重差异，相反，我们的转录组学和组织学分析揭示了亚型之间差异调节机制可能解释这些差异。
Background: Birthweight is a critical predictor of congenital heart disease (CHD) surgical outcomes. Hypoplastic left heart syndrome (HLHS) is cyanotic CHD with known fetal growth restriction and placental abnormalities. Transposition of the great arteries (TGA) is cyanotic CHD with normal fetal growth. Comparison of the placenta in these diagnoses may provide insights on the fetal growth abnormality of CHD.Methods: Clinical data and placental histology from placentas associated with Transposition of the Great Arteries (TGA) were analyzed for gross pathology, morphology, maturity and vascularity and compared to both control and previously analyzed HLHS placentas [1]. RNA was isolated from HLHS, TGA and control placentas and sequenced by Illumina HiSeq.Transcriptome analysis was performed using AltAnalyze. Immunohistochemistry was utilized to assess placental nutrient transporter expression in all three groups.Results: Placental weight was reduced in TGA cases, and demonstrated reduced villous vasculature, immature terminal villi in the parenchyma compared to controls and reflected our previous data from HLHS placentas. However, birth weight was not reduced in TGA cases compared to controls in contrast to the HLHS cohort and birthweight:placental weight ratio was significantly increased in TGA cases but not HLHS compared to control. Transcriptomic and histologic analysis demonstrates reduced cell activity and nutrient transport capability in HLHS but not TGA placentas which appear to increase/maintain these mechanisms.Conclusions: Despite common vascular disturbances in placentas from HLHAs and TGA, these do not account for the disparities in birthweights frequently seen between these CHD subtypes, in contrast our transcriptomic and histologic analyses reveal differentially regulated mechanisms between the subtypes that may explain these disparities.