ADGRG2功能缺失使男性生殖系统中输出小管液体重吸收发生异常，造成精子滞留和输出小管梗阻，从而导致男性不育。我们最新研究发现ADGRG2通过Gq和β-arrestin-1介导的CFTR活性调节输出小管的液体重吸收，是治疗男性不育的一个重要靶点。然而ADGRG2目前仍是孤儿受体，缺乏有效的干预受体活性的策略。我们前期工作筛选了可以成功激活ADGRG2的系链肽，这为ADGRG2的临床应用开启了一个新的窗口。进一步的，我们拟优化ADGRG2系链肽，获得能够外部操控ADGRG2受体活性的有效工具。在此基础上，综合利用多种基因工程小鼠，结合生物化学、分子生物学、药理学和电生理等多种实验方法和手段，在体内深入研究ADGRG2系链肽对输出小管液体重吸收的影响和调控机制，并探讨ADGRG2系链肽对雄性不育小鼠的治疗作用。本研究将进一步深化ADGRG2的临床应用研究，并为男性不育的治疗提供一个新的策略。

Loss of function of ADGRG2 causes abnormal fluid reabsorption of efferent ductules in the male reproductive system, resulting in sperm retention and efferent ductule obstruction, consequently leading to male infertility. Our recent study found that ADGRG2 regulated fluid reabsorption of efferent ductules through CFTR activity mediated by Gq and β-arrestin-1, which was an important target for the treatment of male infertility. However, ADGRG2 is still an orphan receptor and lacks an effective strategy to interfere with its receptor activity. Our previous work screened for a tethered peptide that successfully activated ADGRG2, which opened a new window for the clinical application of ADGRG2. Further, we intend to optimize the ADGRG2-tethered peptide to obtain an effective tool for external control of ADGRG2 receptor activity. On this basis, a variety of genetically engineered mice combined with biochemistry, molecular biology, pharmacology, electrophysiology and other experimental methods will be used to study in vivo the effect and mechanism of ADGRG2-tethered peptide on the fluid reabsorption of efferent ductules, and to explore the therapeutic action of ADGRG2-tethered peptide on male sterile mice. This study will further deepen the research on clinical application of ADGRG2 and provide a new strategy for the male infertility therapy.