Viral-induced placental impairment

描述：(申请人提供)绒毛外的浅表侵袭 滋养层细胞进入子宫壁减少了胎盘的灌注量，导致 胎盘功能障碍，但浅层胎盘侵袭的原因是 未知。需要检验的假设是侵袭性滋养细胞感染 腺相关病毒(AAV)和其他常见病毒在妊娠早期 帮助AAV复制由以下原因引起的产科并发症 胎盘功能障碍，包括自发流产、胎儿生长 限制和先兆子痫。此前，AAV被证明能够感染 未分化和终末分化的滋养层细胞。AAV及其智能交通系统 辅助病毒(即腺病毒、乳头瘤病毒、疱疹病毒和 巨细胞病毒)在流产的滋养层细胞中被发现 早产儿胎膜早破患者的羊水细胞。一个 胎盘病毒感染与病理改变的关系 在胎儿生长受限的病例中被报告，AAVDNA在 子痫前期患者胎盘组织(11/35例)及自发性胎盘组织 早产(8/19例)。最后，90名妇女的血清在第一次 对怀孕三个月的孕妇进行了抗AAV抗体筛查，并对初级AAV进行了检测 感染(IgM抗体的存在)与增加的 自然流产风险(P=0.03)。在这项建议中，病例对照 将进行研究以确定AAV感染是否与 不良生殖后果的范围，体外实验将是 用来检验病毒感染导致病理改变的假说 损害胎盘对子宫壁侵袭的病变。三个具体的 研究目的：1)利用基于聚合酶链式反应的分析方法进行病例对照研究 比较胎盘病毒感染的发生率和相关的病理 妊娠合并胎儿生长受限的妇女的病变 和/或重度子痫前期(病例)和对照组；2)进行嵌套式 妊娠早期母体血清的病例对照研究 对孕妇进行AAV及其辅助病毒抗体筛查，以 早期母亲病毒感染与不良后果之间的相关性 胎盘功能障碍；3)确定AAV和辅助病毒的能力 绒毛外滋养层细胞株的体外感染及其病理学研究 与病毒感染这些细胞和绒毛外植体相关的影响。 这些实验将提供对病毒感染在疾病中的作用的见解 胎盘功能障碍的发病机制。

DESCRIPTION: (Provided By Applicant) Shallow invasion by the extravillous trophoblast into the uterine wall reduces placental perfusion and results in placental dysfunction, but the causes of shallow placental invasion are unknown. The hypothesis to be tested is that infection of invasive trophoblast early in gestation by adeno-associated virus (AAV) and other common viruses that help AAV to replicate causes obstetric complications that result from placental dysfunction, including spontaneous miscarriage, fetal growth restriction, and preeclampsia. Previously, AAV was shown to be able to infect undifferentiated and terminally differentiated trophoblast cells. AAV and its helper viruses (i.e., adenovirus, papillomavirus, herpesvirus, and cytomegalovirus) were discovered in trophoblast cells from miscarriages and in amniocytes from women with preterm premature rupture of the membranes. A relationship between placental viral infections and pathologic abnormalities was reported in cases of fetal growth restriction, and AAV DNA was found in placental tissue from cases of preeclampsia (11/35 cases) and spontaneous preterm birth (8/19 cases). Finally, the serum of 90 women during the first trimester of pregnancy was screened for anti-AAV antibodies, and primary AAV infections (the presence of IgM antibodies) were associated with an increased risk of spontaneous miscarriage (P=0.03). In this proposal, case-control studies will be conducted to determine if AAV infection is associated with a spectrum of adverse reproductive outcomes, and in vitro experiments will be performed to test the hypothesis that viral infection induces pathologic lesions which impair placental invasion of the uterine wall. Three specific aims are proposed: 1) to conduct a case-control study using PCR-based analyses to compare the incidence of placental viral infection and associated pathologic lesions in women whose pregnancies are complicated by fetal growth restriction and/or severe preeclampsia (cases) and controls; 2) to conduct a nested case-control study in which maternal serum during the first trimester of pregnancy is screened for antibodies against AAV and its helper viruses, to correlate early maternal viral infection with adverse outcomes attributed to placental dysfunction; 3) to determine the ability of AAV and helper viruses to infect extravillous trophoblast cell lines in vitro and define the pathologic effects associated with viral infection of these cells and villous explants. These experiments will provide insights into the role of viral infection in the pathogenesis of placental dysfunction.