Pathophysiology of Reproduction, U.O.C., IVF Unit, Azienda Ospedaliera Ospedali Riuniti Marche Nord, Pesaro, Italy.
Laboratory of Genomic Medicine-UILDM, Fondazione Santa Lucia IRCCS, Univ. Tor Vergata; Rome, Italy.
Mol Genet Metab. 2018 Jan;123(1):43-49. doi: 10.1016/j.ymgme.2017.11.009. Epub 2017 Nov 26.
Tangier disease is an autosomal recessive disorder caused by mutations in the ABCA1 gene and characterized by the accumulation of cholesteryl ester in various tissues and a near absence of high-density lipoprotein. The subject in this investigation was a 36-year-old Italian man with Tangier disease. He and his wife had come to the In Vitro Fertilization Unit, Pesaro Hospital (Azienda Ospedaliera Ospedali Riuniti Marche Nord) seeking help regarding fertility issues. The man was diagnosed with severe oligoasthenoteratozoospermia. Testosterone is the sex hormone necessary for spermatogenesis and cholesterol is its precursor; hence, we hypothesized that the characteristic cholesterol deficiency in Tangier disease patients could compromise their fertility. The aim of the study was to therefore to determine if there is an association between Tangier disease and male infertility. After excluding viral, infectious, genetic and anatomical causes of the subject's oligoasthenoteratozoospermia, we performed a hormonal analysis to verify our hypothesis. The patient was found to be negative for frequent bacteria and viruses. The subject showed a normal male karyotype and tested negative for Yq microdeletions and Cystic Fibrosis Transmembrane Conductance Regulator gene mutations. A complete urological examination was performed, and primary hypogonadism was also excluded. Conversely, hormonal analyses showed that the subject had a high level of follicle stimulating hormone and luteinizing hormone, low total testosterone and a significant decline in inhibin B. We believe that the abnormally low cholesterol levels typically found in subjects with Tangier disease may result in a reduced testosterone production which in turn could affect the hormonal axis responsible for spermatogenesis leading to a defective maturation of spermatozoa.
Tangier 病是一种常染色体隐性遗传病，由 ABCA1 基因突变引起，其特征是胆固醇酯在各种组织中蓄积，而高密度脂蛋白（HDL）几乎不存在。本研究的对象是一位 36 岁的意大利 Tangier 病男性患者，他和妻子来到了佩萨罗医院（Azienda Ospedaliera Ospedali Riuniti Marche Nord）的体外受精部门寻求生育问题的帮助。该男子被诊断为严重的少弱畸精子症。睾酮是精子发生所必需的性激素，胆固醇是其前体；因此，我们假设 Tangier 病患者特征性的胆固醇缺乏可能会影响他们的生育能力。本研究的目的是确定 Tangier 病与男性不育之间是否存在关联。在排除了该患者少弱畸精子症的病毒、感染、遗传和解剖原因后，我们进行了激素分析以验证我们的假设。该患者频繁细菌和病毒检测均为阴性。该患者的男性核型正常，Yq 微缺失和囊性纤维化跨膜电导调节因子基因突变检测均为阴性。进行了全面的泌尿科检查，也排除了原发性性腺功能减退症。相反，激素分析显示，该患者的卵泡刺激素和黄体生成素水平较高，总睾酮水平较低，抑制素 B 显著下降。我们认为 Tangier 病患者通常存在的胆固醇水平异常降低可能导致睾酮生成减少，进而影响精子发生的激素轴，导致精子成熟缺陷。
