PATHOGENESIS OF TUBAL FACTOR INFERTILITY

输卵管性不孕症是一种常见的妇科问题，占所有不孕症的15- 30%。大多数输卵管性不孕是由沙眼衣原体引起的。衣原体是美国最常见的性传播疾病。衣原体感染的上生殖道感染通常无症状或亚临床，但可导致输卵管损伤。这些专性的细胞内微生物逃避宿主的防御，引起持续的惰性感染。虽然多项流行病学研究表明衣原体与不孕症之间存在联系，但其潜在的免疫学和发病机制尚不清楚。最近的研究表明，对衣原体60千道尔顿热休克蛋白（hsp 60）的抗体反应与输卵管性不孕有关。另一种10千道尔顿热休克蛋白（hsp10）最近被描述。我们的初步研究表明，不孕妇女也有这种衣原体抗原的抗体。本研究计划的中心假设是对衣原体热休克蛋白的免疫反应改变是输卵管性不孕的原因。本项目的具体目的是：1)测定输卵管因子不孕妇女淋巴细胞对hsp10和hsp60的反应；2)研究hsp10和hsp60在体外输卵管感染模型中的表达。该研究计划是NICHD指导临床科学家发展奖的一部分。该奖项的候选人凯文·奥尔特医生是一位经过临床训练的妇科医生。他对传染病的兴趣源于对输卵管性不孕妇女的关怀。其他常见的妇科疾病，如异位妊娠和盆腔炎，也与衣原体感染有关。通过培训妇科医生将免疫学和微生物学的基本技术应用于衣原体和不孕症的问题，我们可以更好地了解妇女健康中的这一常见问题。

Tubal factor infertility is a common gynecological problem, responsible for 15-30 percent of all infertility. Most cases of tubal factor infertility are caused by Chlamydia trachomatis. Chlamydia is the most common sexually transmitted disease in the United States. Upper genital tract infections with Chlamydia are often asymptomatic or subclinical but can result in fallopian tube damage. These obligate intracellular microorganisms elude host defenses causing a persistent indolent infection. While multiple epidemiological studies have shown a link between Chlamydia and infertility, the underlying immunology and pathogenesis is poorly understood. Recent research has shown that an antibody response to the chlamydial 60-kilodalton heat shock protein (hsp 60) is associated with tubal factor infertility. Another 10-kilodalton heat shock protein (hsp 10) has been recently described. Our initial studies would indicate that infertile women also have antibodies to this chlamydial antigen. The central hypothesis of this research plan is that an altered immune response to chlamydial heat shock proteins is responsible for tubal factor infertility. The specific aims for this project are 1) to determine lymphocyte responses to hsp 10 and hsp 60 in women with tubal factor infertility and 2) to study expression of hsp 10 and hsp 60 in an in vitro model of fallopian tube infection. This research plan is part of a NICHD Mentored Clinical Scientist Development Award. The candidate for this award, Dr. Kevin Ault, is a clinically trained gynecologist. His interest in infectious diseases is the result of caring for women with tubal factor infertility. Other common gynecological diseases, such as ectopic pregnancy and pelvic inflammatory disease, have also been linked to infection with Chlamydia. By training gynecologists to apply fundamental techniques in immunology and microbiology to the problem of Chlamydia and infertility, we can have a better understanding of this common problem in women's health.