精子顶体反应是受精的必要条件，精子顶体反应缺陷会导致精子－透明带穿透失败，从而导致不育。人类透明带是诱导顶体反应的天然因子，我们的前期研究发现，孕酮也可以引起顶体反应，对于预测体外受精率有一定价值。我们打算从三方面对孕酮诱发的顶体反应机制及相关调控进行深入研究：（1）比较透明带和孕酮在诱导顶体反应信号途径方面的异同，对PKC等因子活性进行比较，并通过基于BioPORTER技术所引起的的IP3敏感的钙离子通道能力的变化对透明带和孕酮诱发的顶体反应的作用进行比较；（2）建立孕酮诱发的顶体反应与精子穿透透明带的能力和体外受精率之间的关系；（3）确定信号传导对透明带和孕酮诱发的缺陷性顶体反应的作用，观察对于DZPIAR患者的精液给予顶体反应相关的信号级联的激动剂后的精子-透明带穿透能力的变化。希望通过本研究为临床诊断DZPIAR提供方便、价廉、可靠的方法，并为受精缺陷患者的治疗提供新的思路。

KEY ISSUES.During fertilization, spermatozoon binds to and penetrates the zona pellucdia (ZP). The penetration of ZP requires the release of acrosomal enzymes from spermatozoa by the process of acrosome reaction. Disordered acrosome reaction causes failure of sperm–ZP penetration resulting in infertility. In standard in-vitro fertilization (IVF), defective sperm-ZP penetration due to sperm abnormalities is a major cause of fertilization problem. Consistently, ZP-induced acrosome reaction has been reported to be highly correlated with fertilization rates in vitro. ..The identification of disordered acrosome reaction is a challenge to reproductive medicine specialists. It can occur in patients with normal semen analysis and ZP binding. A practical diagnostic method for these patients is not yet available. Most previous studies used ZP as an acrosome reaction inducer to diagnose disordered acrosome reaction. Although the method has proven to be clinically useful, the limited availability of human ZP makes the assay impractical for routine clinical use. ..HYPOTHESIS.Progesterone is present at high level at the site of fertilization and induces acrosome reaction in sperm of human and other species. However, little is known on its relationship with fertilization rates in vitro. The diagnostic potential of progesterone-induced acrosome reaction for disordered acrosome reaction is unclear. In this proposal, we hypothesize that progesterone-induced acrosome reaction is a useful indicator in addition to routine semen analysis for diagnosis of patients with disordered acrosome reaction. Three objectives will be provided to test the hypothesis. They are: 1) To compare the signal pathways mediated by ZP and progesterone on inducing acrosome reaction; 2) To establish the relationship between progesterone-induced acrosome reaction with the ability of sperm to penetrate the ZP and fertilization rate in vitro; and 3) To determine the role of signal transduction on defective ZP- and progesterone-induced acrosome reaction...LONG TERM IMPACT.Treatment of human infertility using assisted reproductive technology with standard IVF and intracytoplasmic sperm injection (ICSI) have been very successful. The choice between standard IVF and ICSI is generally based on the results of semen analysis. However, standard semen analysis provides only limited information about sperm fertilizing ability and disordered acrosome reaction can occur in patients with normal semen analysis. To improve the clinical management of these patients, it is important to diagnose disordered acrosome reaction by reliable test before commencing assisted reproduction treatment. The proposed project will study the use of progesterone-induced acrosome reaction as a sperm function test for predicting the fertilization potential of semen samples. It will also give indication to whether modulation of sperm acrosome reaction-associated signaling pathways can be applied clinically to enhance fertilization.