Placenta: Ethanol and HIV

胎盘：乙醇和艾滋病毒

• 批准号: 6753449
• 负责人: Richard Kermit Miller
• 金额: $ 15.75万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至 2006-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6753449
• 关键词: HIV infections; alcoholic beverage consumption; clinical research; disease /disorder etiology; drug detection; embryo /fetus pharmacology; embryo /fetus toxicology; epidemiology; ethanol; female; human immunodeficiency virus 1; human pregnant subject; interview; membrane permeability; organ culture; patient oriented research; perfusion; placenta; placental transfer; pregnancy; vertical transmission; women' s health

DESCRIPTION (provided by applicant): The human placenta normally serves as a barrier to direct transmission of viruses from the maternal circulation to the fetus. This is confirmed by the fact that approximately 25% of the infected babies of untreated mothers positive for the HIV virus are infected in utero. What determines the apparent differential transmission in different pregnancies is unknown. It has been suggested that the placenta's protective role may be compromised by maternal exposure to ethanol. While no data are available to suggest how this might occur, there are two obvious hypotheses. First, chronic exposure to ethanol might injure the placenta, producing a long-term malfunction. Second, acute exposure might result in a temporary failure of protective function. We propose to test both hypotheses in a human placental perfusion system. Passage of the HIV virus from the maternal circulation to the fetal circulation will be quantified over an 18 hour perfusion in placentae of mothers who report three or more alcoholic drinks per day versus those who report no exposure to ethanol. If ethanol-exposed placentae permit more virus to cross to the fetal circulation than unexposed placentae, chronic maternal ethanol exposure will be implicated as a factor in passage of the HIV virus. In half the placentae from each maternal group, ethanol will be added directly to the perfusion medium. If perfusions with ethanol exhibit increased passage of virus, acute exposure will be implicated as playing a role in transmission. Because there is evidence that transmission occurs only when the placenta itself is infected, the same chronic and acute exposure conditions will be studied in placentae experimentally infected with HIV-1 and monitored in human placental explant cultures. These experiments will provide tests of a third important hypothesis: that ethanol exposure increases the risk of transmission by increasing the degree of infection in the placenta. The experiments proposed will provide the first evidence on whether ethanol plays a role in direct transmission of the HIV virus to the fetus.

描述（由申请人提供）： 人类胎盘通常作为病毒从母体循环直接传播到胎儿的屏障。这一点得到以下事实的证实：未经治疗的艾滋病毒阳性母亲的受感染婴儿中，约有25%是在子宫内感染的。是什么决定了不同妊娠中的明显差异传播尚不清楚。有人认为，胎盘的保护作用可能会受到母亲接触乙醇的影响。虽然没有数据表明这是如何发生的，但有两个明显的假设。首先，长期接触乙醇可能会损伤胎盘，产生长期功能障碍。其次，急性暴露可能导致保护功能暂时失效。我们建议在人类胎盘灌注系统中测试这两种假设。将在18小时灌注期间，对报告每天饮酒3次或以上的母亲与报告未暴露于乙醇的母亲的胎盘中HIV病毒从母体循环到胎儿循环的传递进行定量。如果暴露于乙醇的胎盘比未暴露的胎盘允许更多的病毒进入胎儿循环，则母体长期暴露于乙醇将被认为是HIV病毒通过的一个因素。在每个母体组的一半胎盘中，将乙醇直接加入灌注培养基中。如果用乙醇灌注显示出增加的病毒通过，则急性暴露将被认为在传播中起作用。因为有证据表明，只有当胎盘本身被感染时才会发生传播，所以将在实验感染HIV-1的胎盘中研究相同的慢性和急性接触条件，并在人胎盘外植体培养物中监测。这些实验将提供第三个重要假设的检验：乙醇暴露通过增加胎盘感染程度来增加传播风险。这项实验将首次证明乙醇是否在艾滋病毒直接传播给胎儿的过程中发挥作用。