性发育异常发病机制的研究进展

Research Progress of Pathogenesis of Disorders of Sex Development

正常的性腺分化可分为3个过程:原始性腺形成、性别决定和卵巢/睾丸发育。在任一环节中,基因表达或调控发生异常均有可能导致性发育异常疾病的发生。性发育异常是指染色体、性腺和解剖性别不典型。随着分子生物学技术的发展,不断地发现新的基因或信号通路参与性腺分化和发育,如SRY、SF1、WT1、Sox9等基因与睾丸发育密切相关,Wnt/Rspo1/B连环蛋白通路、Dax1、Foxl2等基因在卵巢分化中发挥着重要作用,一些非编码RNA和转化生长因子也有重要的调节功能,且睾丸和卵巢发育均为主动过程,即使在出生后因某些基因的改变两者间也可出现横向分化。这些为揭示性分化异常的发病机制提供了可能。

Normal sex differentiation includes the tbrrnation ot primordial gonads, sex determination and ovarian or testis development. The misregulation of gene expression in each process may lead to the disorders of sex development （DSD）. DSD is defined by congenital conditions of the atypical chromosome,gonadal or anatomical sex. With the development of molecular biotechnology,more and more genes and signaling pathways are discovered to be involved in sex differentiation and development. For example,some genes such as SRY, SF1 ,WT1 and Sox9 are closely related to testieular development, while others such as Wnt/Rspol/B-catenin pathway and genes like Daxl ,Foxl2 play an important role in ovarian differentiation. Some none-coding RNA and transforming growth factor also regulate the sexual differentiation. The developments of both testis and ovary are active, and transverse differentiation can appear according to some abnormal genes even after birth.