UPSEBP, A PROFERTILITY PROTEIN IN HUMAN SEMEN

描述（由申请人提供）：低生育能力每年影响约125万男性，尽管许多人射精数量合理的运动和正常精子。项目目标是低成本的治疗方法，以增加通过宫内人工授精怀孕的可能性。我们假设一些不育男性的精子中UPSEBP（通用初级精子-卵子结合蛋白）不足。合成肽，基于假定的人类UPSEBP序列，增加了28个新鲜患者精液样本中46%的人类精子与带样底物的结合。创新的肽序列提高了4种模型物种的生育能力（例如，在牛的IUI后提高了14个单位；在牛和小鼠的IVF中等于或等于13个单位）。具体目的是：(1)测定人精浆中UPSEBP的氨基酸序列；(2)确定患者和育龄男性精浆中内源性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分子符合自然序列，并作为生物分类。完成后将允许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功效（ii期），以及使用IUI或IVF进行临床试验（iii期）。

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).