UPSEBP, A PROFERTILITY PROTEIN IN HUMAN SEMEN

描述（由申请人提供）：低生育力每年影响超过125万男性，尽管许多人射出合理数量的活动和正常精子。项目目标是通过IUI增加妊娠概率的低成本治疗。我们假设一些不育男性的精子上UPSEBP（通用初级精卵结合蛋白）不足。基于人类UPSEBP推测序列的合成肽，在28份新鲜患者精液样本中，增加了46%的人类精子与透明带样基质的结合。创新的肽序列增加了4种模型物种的生育力（例如，牛IUI后增加14%单位;牛和小鼠IVF中等于或>13单位）。具体目标是：（1）测定人精浆中UPSEBP氨基酸序列;（2）确定患者和生育男性精浆中内源性UPSEBP的量范围。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的。人UPSEBP的分离和测序将允许合成分子符合天然序列，并分类为生物制品。完成后将允许评价合成肽增加患者精子与人透明质酸或类似合成底物结合的功效（II期），以及使用IUI或IVF的临床试验（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).