胎儿生长受限影像评价体系建立与IGF-2/CDKN1C基因表达

Fetal growth restriction (FGR) is mainly caused by insufficient placental function, which is associated with increased risk of stillbirth, postnatal disability, and impaired motor and cognitive functions, and will affect the lifelong health for babies, with increased associated risk of hypertension, cardiovascular disease, stroke, and diabetes in adulthood. Currently, early delivery is the only treatment for FGR, resulting in further risks of iatrogenic morbidity and mortality. The traditional monitoring means high false positive rate, and easily lead to excessive clinical intervention. Our research group in recent years, using nuclear magnetic resonance (MRI) technology has been established evaluation model of fetal circulation changes of normal and congenital heart disease. This project based on the proposed application of ultrasound and MRI to establish late onset FGR image evaluation system, in order to improve the effectiveness of the diagnosis of FGR, so as to improve the perinatal pregnancy outcomes, establish new method with clinical application value for evaluation of maternal-fetal circulation changes. At the same time observe the different phenotypes of insulin-like growth factor-2 (IGF-2) /Cyclin-dependent kinase inhibitor 1c (CDKN1C ) imprinting gene expression levels, in different types of fetal placental tissues by imaging technology to explore the correlation of IGF - 2 / CDKN1C expression model with FGR, and to analysis the mechanism in the process of FGR pathological.

胎儿生长受限（FGR）主要由胎盘功能不足引起，可增加死产的风险，导致产后残疾、运动和认知功能受损，同时会对婴儿的终身健康产生影响，增加成年后发生高血压、心血管疾病、中风和糖尿病的风险。目前早期分娩胎儿是唯一的治疗手段，但使医源性发病率和死亡率的风险增加。传统的监测手段假阳性率高，易导致过度临床干预。本研究组近年采用核磁共振技术（MRI）已建立评价正常及先心病胎儿循环变化的模型，本项目在此基础上拟应用超声和MRI建立迟发型FGR影像评价体系，以提高胎儿生长受限的诊断效能，从而改善围产儿的妊娠结局，建立具有临床应用价值的评价FGR的母胎循环变化的新方法；同时观察影像技术所识别的不同表型胎儿胎盘组织中胰岛素样生长因子-2（IGF-2）/细胞周期素依赖的激酶抑制剂-1c（CDKN1C）印记基因表达水平，探讨IGF-2/CDKN1C表达模式与FGR的相关性，并分析其在FGR病理过程中的作用机制。

宫内生长受限胎儿是通过减慢生长降低氧供给和氧消耗来适应慢性缺氧。肺血流减少与胎儿循环氧重新分布有关，肺血流减少与胎儿循环氧重分布有关。肺血流减少和肺动脉分支频谱形态改变可能是胎儿缺氧的早期征象。完成35例正常胎儿及15例宫内生长受限胎儿的循环评价，计算胎儿氧供给及氧消耗，大脑氧供给及氧消耗，并获取大脑氧摄取分数。结果显示宫内生长受限胎儿氧供给和氧消耗明显降低，大脑氧供给明显降低。宫内生长受限组的氧摄取分数明显增加，但两组间无统计学差异，说明尽管宫内生长受限胎儿大脑氧供给明显降低，大脑氧消耗无明显差异。宫内生长受限胎儿是通过减慢生长降低氧供给和氧消耗来适应慢性缺氧。这种从急性到慢性适应的转变已经在胎羊身上得到证实。因此，磁共振成像用于检测严重的胎盘功能不全是可行的。同时发现胎儿大脑氧供给与新生儿脑容量呈正相关，说明尽管存在大脑保护效应，慢性缺氧仍然对宫内生长受限胎儿的大脑发育产生一定影响，这方面值得进一步深入探讨。此外，我们利用异基因交配小鼠模型（BALB/c ♀ x C57BL/6 ♂），发现PDL-1阻断后，小鼠的胚胎丢失率显著增加，并且CD4+CXCR5hiPD-1hiFoxp3+ Tfr细胞的比例也显著增加，从而说明PD-1/PDL-1信号通路对胎儿正常发育发挥重要的作用。

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