Retinoic Acid in Male Infertility

视黄酸在男性不育中的作用

• 批准号: 9230783
• 负责人: John K. Amory
• 金额: $ 12.75万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-05-01 至 2020-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9230783
• 关键词: Address; Affect; Anabolism; Animal Model; Animals; Area; Award; Biological Assay; Biopsy; Clinical; Clinical Trials; Coupled; Couples; Development; Enrollment; Faculty; Fertility; Fertilization in Vitro; Fostering; Future; Goals; Grant; Growth; Human; Impairment; Infertility; Intracytoplasmic Sperm Injections; Isotretinoin; Knowledge; Male Contraceptive Agents; Male Infertility; Medical; Mentors; Mentorship; Methods; Molecular Abnormality; Morphology; Observational Study; Operative Surgical Procedures; Oral; Placebos; Play; Population; Principal Investigator; Procedures; Reproduction; Research; Research Personnel; Retrieval; Role; Scrotum; Secondary to; Seminal fluid; Spermatogenesis; Spermiogenesis; Testicular Tissue; Testing; Training; Translational Research; Tretinoin; Work; cell motility; experimental study; improved; infertility treatment; liquid chromatography mass spectrometry; male; man; men; next generation; novel; novel strategies; patient oriented research; pilot trial; prospective; public health relevance; sperm cell; sperm quality

 DESCRIPTION (provided by applicant): The overarching goal of this application for a K24 Midcareer Investigator in Patient-Oriented Research is to foster training of promising junior investigators in high quality patient-oriented research in male reproduction. The proposed principal investigator, Dr. Amory, has established himself as a gifted researcher and is a dedicated mentor to junior faculty and trainees. With this award, Dr. Amory hopes to continue as a leader in patient-oriented research in the area of male reproduction and to enhance the educational training of clinical trainees through hands-on mentorship, facilitating their individua growth as well as the future of translational research in male reproduction. Infertility affects 10 15% of all couples, and infertility attributable to the male partner accounts for 30-40% of all cases of infertility. The most common form of male infertility involves some type of impairment in spermatogenesis. Unfortunately, most men with infertility do not have a medically treatable cause. Surgical sperm extraction coupled with either in vitro fertilization or intra-cytoplasmic sperm injection offers hope of fertility; however, these procedures are invasive, expensive, unsuccessful in many cases, and don't address the underlying cause of infertility. Therefore, new approaches to the treatment of male infertility are needed. The objective of the work proposed in this application is to obtain knowledge useful to understand the role of retinoic acid in spermatogenesis and male infertility. It is well established in animal models that testicular biosynthesis of retinoic acid is required for spermatogonial differentiation, spermiogenesis and spermiation. However, in contrast to the situation in experimental animals, there has been almost no work examining the role of retinoic acid in human spermatogenesis. Recently, our group found that intratesticular retinoic acid is significantly reduced in men who have sub-normal sperm parameters, suggesting that intratesticular retinoic acid deficiency may be related to impaired spermatogenesis in man. With this grant, we propose to examine the role of intratesticular retinoic acid in men presenting with male infertility. In the first aim of this proosal, we will investigate the relationship between intratesticular retinoic acid and spermatogenesis using an observational study in testicular tissue from men undergoing sperm retrieval procedures for infertility treatment. In the second aim, we will conduct a pilot clinical trial of retinoic acid administration to men with infertility from poor sperm quality to determine whether retinoic acid improves ejaculated sperm parameters. Taken together, these experiments will greatly improve our understanding of the relationship between intratesticular retinoic acid and spermatogenesis in man, and have the potential to initiate a novel medical approach to the treatment of male infertility.

 描述（由申请人提供）：本申请的总体目标是在以患者为导向的研究中为K24职业中期研究者培养有前途的初级研究者在男性生殖方面进行高质量的以患者为导向的研究。拟议的首席研究员，博士阿莫里，已确立自己作为一个天才的研究人员，是一个专门的导师，初级教师和学员。凭借这一奖项，阿莫里博士希望继续作为男性生殖领域以患者为导向的研究的领导者，并通过实践指导加强临床学员的教育培训，促进他们的个人成长以及男性生殖转化研究的未来。不孕症影响10 15%的夫妇，男性伴侣造成的不育占所有不育病例的30-40%。男性不育症最常见的形式涉及精子发生的某种类型的障碍。不幸的是，大多数男性不育症没有医学上可治疗的原因。手术精子提取结合体外受精或胞质内精子注射提供了生育的希望;然而，这些程序是侵入性的，昂贵的，在许多情况下不成功，并且不能解决不孕症的根本原因。因此，需要治疗男性不育症的新方法。本申请中提出的工作的目的是获得有助于理解视黄酸在精子发生和男性不育中的作用的知识。在动物模型中已经确定，精原细胞分化、精子发生和精子形成需要睾丸生物合成维甲酸。然而，与实验动物的情况相反，几乎没有研究维甲酸在人类精子发生中的作用。最近，我们的研究小组发现，睾丸内维甲酸显着减少的男性谁有低于正常的精子参数，这表明睾丸内维甲酸缺乏可能与受损的精子发生在man. With此补助金，我们建议检查睾丸内维甲酸的作用，在男性不育症。在本研究的第一个目的中，我们将通过对接受精子回收手术治疗不育症的男性睾丸组织进行观察性研究，探讨睾丸内维甲酸与精子发生之间的关系。在第二个目标中，我们将对精子质量差的不育男性进行维甲酸给药的初步临床试验，以确定维甲酸是否能改善射出精子的参数。总之，这些实验将大大提高我们对睾丸内维甲酸和精子发生之间关系的理解，并有可能启动一种新的医学方法来治疗男性不育症。