UPSEBP, A PROFERTILITY PROTEIN IN HUMAN SEMEN

描述(申请人提供)：每年影响125万名男性，尽管许多人射出相当数量的可活动和正常的精子。项目目标是低成本的治疗，以增加通过IUI怀孕的可能性。我们假设一些不育男性精子上的UPSEBP(通用初级精子-卵子结合蛋白)不足。基于推测的人类UPSEBP序列的合成肽，增加了28例新鲜患者精液样本中46%的人精子与带状底物的结合。创新的多肽序列提高了4个模式物种的生育力(例如，牛的IUI后增加了14个百分比单位；在牛和小鼠的试管受精中等于或&gt；13个单位)。具体目标是：(1)测定人精浆中UPSEBP的氨基酸序列；(2)建立患者和生育男子精浆中内源性UPSEBP的含量范围。对患者和有生育能力的男性精液中UPSEBP的测量应该表明这个问题是真实存在的。人类UPSEBP的分离和测序将使合成的分子与自然序列一致，并被归类为生物。完成后，将可以评估合成肽增加患者精子与人类透明带或类似合成底物结合的有效性(第二阶段)，以及使用IUI或试管受精的临床试验(第三阶段)。

DESCRIPTION (provided by applicant): Subfertility impacts >1.25 million men annually, although many ejaculate reasonable numbers of motile and normal sperm. Project goal is low-cost therapy to increase probability of pregnancy via IUI. We hypothesize some infertile men have insufficient UPSEBP (universal primary sperm-egg binding protein) on their sperm. Synthetic peptide, based on presumed sequence of human UPSEBP, increased binding of human sperm to a zona-like substrate for 46% of 28 samples of fresh patient semen. The innovative peptide sequence increased fertility with 4 model species (e.g., by 14 percentage units after IUI of cattle; equal to or >13 units in IVF for cattle and mice). Specific Aims are: (1) determine amino acid sequence of UPSEBP in human seminal plasma; and (2) establish range in amount of endogenous UPSEBP in seminal plasma from patients and fertile men. Measurement of UPSEBP in semen from patients and fertile men should show that the problem is real. Isolation and sequencing of human UPSEBP will allow the synthetic molecule to conform with the natural sequence, and classification as a biologic. Completion will allow evaluation of efficacy of synthetic peptide to increase binding of patient sperm to human zona pellucida or similar synthetic substrates (Phase-II) , and clinical trials using IUI or IVF (Phase-III).