MOLECULAR SIZE SELECTIVITY OF IMMATURE PLACENTA

未成熟胎盘的分子大小选择性

• 批准号: 3329119
• 负责人: JOB J. FABER
• 金额: $ 9.35万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-08-01 至 1996-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3329119
• 关键词: blood chemistry; chorioallantoic membrane; diffusion; early embryonic stage; electron microscopy; gestational age; guinea pigs; laboratory rabbit; laboratory rat; membrane permeability; molecular size; placenta; placental transfer; radiotracer; scintillation counter; statistics /biometry

The long-term objective is to obtain quantitative information on the permeability of the immature placenta in animals with hemochorial placentas. The expectation is that the results on immature placentas can be extrapolated to the early human placenta, like the results on mature hemochorial placentas could be extrapolated to the mature human placenta. The first hypothesis to be tested is that the immature placenta evolves through stages of changing permeability and changing molecular selectivity. The second hypothesis is that the permselectivities of the various types of hemochorial placentas are strongly related to stage of conceptual development, possibly more so than to differences in histological structure. Specific aims are to determine the permeability of the early placenta to hydrophilic, metabolically inert, charged and non-charged probes with molecular radii from 0.2 to 1.22 nanometers. Placentas of 0.3, 0.4, 0.5, 0.6, and 0.7 gestational age will be studied in the guinea pig, rabbit and rat. The hemomonochorial human placenta is structurally closely related to the guinea pig placenta. Nevertheless, its molecular size selectivity is more closely mirrored in the hemodichorial placenta of the rabbit and the hemotrichorial placenta of the rat than in the placenta of the guinea pig. For these reasons all 3 hemochorial species will be studied. The rules that govern diffusional exchange apply to all materials traversing the placental barrier. For this reason, the study of diffusional transfer provides information on more materials at lesser cost than the study of carrier mediated transfers. The study of the permeability of the early placenta will help to predict the exposure levels of the early human embryo to therapeutic xenobiotics such as antiviral/anti HIV agents and teratogens because preliminary data indicate that it is far less permeable than its mature counterpart.

长期目标是获得关于 血绒膜炎动物未成熟胎盘的通透性 胎盘 我们期望在未成熟胎盘上的结果可以 可以外推到早期人类胎盘，就像成熟胎盘的结果一样。 血绒膜胎盘可外推至成熟的人胎盘。 第一个要检验的假设是未成熟胎盘 通过改变渗透性和改变分子 选择性 第二个假设是， 各种类型的血绒膜胎盘与妊娠期密切相关。 概念的发展，可能比在 组织结构 具体的目的是确定渗透性的早期 胎盘亲水性、代谢惰性、带电和不带电 分子半径从0.2到1.22纳米的探针。 胎盘 将在豚鼠中研究0.3、0.4、0.5、0.6和0.7胎龄 猪，兔子和老鼠。 人血单绒膜胎盘的结构 与豚鼠胎盘密切相关。 然而，其分子 大小选择性在胎盘出血中更能反映出来 兔的血绒胎盘和大鼠的血绒胎盘比 豚鼠的胎盘 由于这些原因，所有3种血绒膜动物 将被研究。 支配扩散交换的规则适用于所有材料 穿过胎盘屏障 因此，研究 扩散转移以更低的成本提供更多材料的信息。 成本比研究载体介导的转移。 的研究 早期胎盘的渗透性将有助于预测暴露 早期人类胚胎对治疗性异生物质的水平， 抗病毒/抗艾滋病毒药物和致畸剂，因为初步数据 表明其渗透性远低于其成熟对应物。