卵巢睾丸综合征是一种罕见的性发育障碍，其特征是睾丸和卵巢组织的存在。人睾丸组织的组织学特征由包含TSPY阳性生殖细胞和Sox9阳性睾丸支持细胞的间质组织包围的生精索或小管明确定义，间质组织包含细胞色素P450阳性睾丸间质细胞和平滑肌α-肌动蛋白阳性肾小管周围肌样细胞。卵巢的组织学特征可以通过生殖细胞巢和卵泡的发育来定义。与睾丸相反，卵巢缺乏明确的特定蛋白质标记，颗粒细胞标记FOXL2是最广泛使用的。在实践中,定义卵巢的卵巢成分可能非常困难。我们通过在异种移植模型中结合胎儿人睾丸和卵巢来开发人卵睾丸综合征模型。卵腺异种移植物在睾丸切除的无胸腺裸鼠的肾囊下生长6-32周，并与年龄匹配的胎儿睾丸和卵巢对照移植物一起生长。通过组织学分析了40个卵核异种移植物及其对照，免疫组织化学，和荧光原位杂交以确定移植物内细胞的蛋白质表达和核型。基于上文定义的睾丸特异性和卵巢特异性标志物,卵腺异种移植物表现出可识别的睾丸和卵巢组织。异种移植物模拟了双极卵睾丸，其中睾丸和卵巢元素保留了它们各自的组织学特征，并被明确的边界隔开。这与先前在文献中描述的分隔的卵睾丸形成对比，其中睾丸组织被卵巢组织包围，或睾丸和卵巢组织散布在整个性腺中的混合组织学。总之,我们已经描述了卵睾丸的人体模型，这将使人们对卵睾丸的发育有更深入的了解，并有助于对卵睾丸综合征进行更准确的诊断。
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.
