Sharpe Richard M, McKinnell Chris, Kivlin Catrina, Fisher Jane S
MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, The Chancellor's Building, University of Edinburgh, 49 Little France Crescent, Old Dalkeith Road, Edinburgh EH16 4SB, UK.
Reproduction. 2003 Jun;125(6):769-84. doi: 10.1530/rep.0.1250769.
Disorders of testicular function may have their origins in fetal or early life as a result of abnormal development or proliferation of Sertoli cells. Failure of Sertoli cells to mature, with consequent inability to express functions capable of supporting spermatogenesis, is a prime example. In a similar way, failure of Sertoli cells to proliferate normally at the appropriate period in life will result in reduced production of spermatozoa in adulthood. This review focuses on the control of proliferation of Sertoli cells and functional maturation, and is motivated by concerns about 'testicular dysgenesis syndrome' in humans, a collection of common disorders (testicular germ-cell cancer, cryptorchidism, hypospadias and low sperm counts) which are hypothesized to have a common origin in fetal life and to reflect abnormal function of Sertoli (and Leydig) cells. The timing of proliferation of Sertoli cells in different species is reviewed, and the factors that govern the conversion of an immature, proliferating Sertoli cell to a mature, non-proliferating cell are discussed. Protein markers of maturity and immaturity of Sertoli cells in various species are reviewed and their usefulness in studies of human testicular pathology are discussed. These markers include anti-Mullerian hormone, aromatase, cytokeratin-18, GATA-1, laminin alpha5, M2A antigen, p27(kip1), sulphated glycoprotein 2, androgen receptor and Wilms' tumour gene. A scheme is presented for characterization of Sertoli-cell only tubules in the adult testis according to whether or not there is inherent failure of maturation of Sertoli cells or in which the Sertoli cells have matured but there is absence, or acquired loss, of germ cells. Functional 'de-differentiation' of Sertoli cells is considered. It is concluded that there is considerable evidence to indicate that disorders of maturation of Sertoli cells may be a common underlying cause of human male reproductive disorders that manifest at various life stages. This recognition emphasizes the important role that animal models must play to enable identification of the mechanisms via which failure of proliferation and maturation of Sertoli cells can arise, as this failure probably occurs in fetal life.
睾丸功能障碍可能源于胎儿期或生命早期，这是由支持细胞异常发育或增殖导致的。支持细胞未能成熟，进而无法表达支持精子发生的功能，就是一个典型例子。同样，支持细胞在生命中的适当阶段未能正常增殖，将导致成年期精子生成减少。本综述聚焦于支持细胞增殖的调控和功能成熟，其动因是对人类“睾丸发育不全综合征”的关注，这是一组常见疾病（睾丸生殖细胞癌、隐睾症、尿道下裂和精子数量少），据推测它们在胎儿期有共同起源，并反映支持（和间质）细胞的异常功能。本文综述了不同物种中支持细胞增殖的时间，并讨论了控制未成熟、增殖性支持细胞转变为成熟、非增殖性细胞的因素。综述了不同物种中支持细胞成熟和未成熟的蛋白质标志物，并讨论了它们在人类睾丸病理学研究中的用途。这些标志物包括抗苗勒管激素、芳香化酶、细胞角蛋白-18、GATA-1、层粘连蛋白α5、M2A抗原、p27（kip1）、硫酸化糖蛋白2、雄激素受体和威尔姆斯肿瘤基因。提出了一个方案，根据支持细胞是否存在内在成熟障碍，或支持细胞已成熟但生殖细胞缺失或获得性丧失，来对成年睾丸中仅含支持细胞的小管进行特征描述。文中考虑了支持细胞的功能性“去分化”。得出的结论是，有大量证据表明，支持细胞成熟障碍可能是人类男性生殖障碍在不同生命阶段表现出来的一个常见潜在原因。这一认识强调了动物模型在确定支持细胞增殖和成熟失败可能发生的机制方面必须发挥的重要作用，因为这种失败可能发生在胎儿期。
