Baskin Laurence, Cao Mei, Derpinghaus Amber, Aksel Sena, Overland Maya, Li Yi, Cunha Gerald
University of California, Department of Urology, 550 16th St, 5th Floor, Mission Hall Pediatric Urology, San Francisco, CA, 94158, USA.
University of California, Department of Urology, 550 16th St, 5th Floor, Mission Hall Pediatric Urology, San Francisco, CA, 94158, USA.
Differentiation. 2023 Jan-Feb;129:60-78. doi: 10.1016/j.diff.2021.12.003. Epub 2021 Dec 20.
Ovotesticular syndrome is a rare disorder of sex development characterized by the presence of testicular and ovarian tissue. The histologic characteristics of human testicular tissue are well defined by the presence of seminiferous cords or tubules containing TSPY-positive germ cells and Sox9-positive Sertoli cells surrounded by interstitial tissue containing cytochrome P450-positive Leydig cells and smooth muscle α-actin-positive peritubular myoid cells. The histological characteristics of the ovary can be defined by germ cell nests and the development of follicles. In contrast to the testis, the ovary has a paucity of defined specific protein markers, with the granulosa cell marker FOXL2 being the most widely used. In practice, defining the ovarian component of the ovotestis can be quite difficult. We developed a model of human ovotesticular syndrome by combining fetal human testis and ovary in a xenograft model. Ovotesticular xenografts were grown under the renal capsules of gonadectomized athymic nude mice for 6-32 weeks along with age matched control grafts of fetal testis and ovary. Forty ovotesticular xenografts and their controls were analyzed by histology, immunohistochemistry, and fluorescent in situ hybridization to determine the protein expression and karyotype of the cells within the grafts. The ovotesticular xenografts exhibited recognizable testicular and ovarian tissue based on testis-specific and ovary-specific markers defined above. The xenografts simulated a bipolar ovotestis in which the testicular and ovarian elements retain their separate histological characteristics and are separated by a well-defined border. This contrasts with the compartmentalized ovotestis previously described in the literature where the testicular tissue is surrounded by ovarian tissue or a mixed histology where testicular and ovarian tissues are interspersed throughout the gonad. In conclusion, we have characterized a human model of ovotestis which will allow a deeper understanding of ovotestis development in humans and facilitate a more accurate diagnosis of the ovotesticular syndrome.
卵睾综合征是一种罕见的性发育障碍，其特征是存在睾丸和卵巢组织。人类睾丸组织的组织学特征通过含有TSPY阳性生殖细胞的生精索或小管以及由含有细胞色素P450阳性的睾丸间质细胞和平滑肌α-肌动蛋白阳性的睾丸周肌样细胞组成的间质组织包围的Sox9阳性支持细胞来明确界定。卵巢的组织学特征可通过生殖细胞巢和卵泡的发育来定义。与睾丸不同，卵巢缺乏明确的特异性蛋白质标志物，颗粒细胞标志物FOXL2是使用最广泛的。在实际操作中，确定卵睾的卵巢成分可能相当困难。我们通过在异种移植模型中结合胎儿人类睾丸和卵巢，建立了人类卵睾综合征模型。将卵睾异种移植在去性腺的无胸腺裸鼠的肾包膜下生长6至32周，同时与年龄匹配的胎儿睾丸和卵巢对照移植物一起培养。通过组织学、免疫组织化学和荧光原位杂交分析了40个卵睾异种移植物及其对照，以确定移植物内细胞的蛋白质表达和核型。基于上述睾丸特异性和卵巢特异性标志物，卵睾异种移植物表现出可识别的睾丸和卵巢组织。异种移植物模拟了一种双极性卵睾，其中睾丸和卵巢成分保留其各自独立的组织学特征，并由明确的边界分隔。这与文献中先前描述的分区化卵睾形成对比，在分区化卵睾中，睾丸组织被卵巢组织包围，或者是一种混合组织学，其中睾丸和卵巢组织散布在整个性腺中。总之，我们已经描述了一种人类卵睾模型，这将有助于更深入地了解人类卵睾的发育，并有助于更准确地诊断卵睾综合征。
