Moses Malcolm M, Behringer Richard R
Department of Genetics, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA.
Environ Epigenet. 2019 Sep 25;5(3):dvz017. doi: 10.1093/eep/dvz017. eCollection 2019 Jul.
Mammalian embryos initially develop progenitor tissues for both male and female reproductive tract organs, known as the Wolffian ducts and the Müllerian ducts, respectively. Ultimately, each individual develops a single set of male or female reproductive tract organs. Therefore, an essential step for sex differentiation is the regression of one duct and growth and differentiation of the other duct. In males, this requires Müllerian duct regression and Wolffian duct growth and differentiation. Müllerian duct regression is induced by the expression of , encoding anti-Müllerian hormone, from the fetal testes. Subsequently, receptor-mediated signal transduction in mesenchymal cells surrounding the Müllerian duct epithelium leads to duct elimination. The genes that induce transcription and the downstream signaling that results from activity form a pathway. However, the molecular details of this pathway are currently unknown. A set of essential genes for AMH pathway function has been identified. More recently, transcriptome analysis of male and female Müllerian duct mesenchyme at an initial stage of regression has identified new genes that may mediate elimination of the Müllerian system. The evidence taken together can be used to generate an initial gene regulatory network describing the pathway for Müllerian duct regression. An gene regulatory network will be a useful tool to study Müllerian duct regression, sex differentiation, and its relationship to environmental influences.
哺乳动物胚胎最初会发育出分别用于雄性和雌性生殖道器官的祖细胞组织,即中肾管和苗勒管。最终,每个个体都会发育出一套单一的雄性或雌性生殖道器官。因此,性别分化的一个关键步骤是一条管道的退化以及另一条管道的生长和分化。在雄性中,这需要苗勒管退化以及中肾管生长和分化。苗勒管退化是由胎儿睾丸中编码抗苗勒管激素的基因表达所诱导的。随后,苗勒管上皮周围间充质细胞中的受体介导信号转导导致管道消除。诱导该基因转录以及该基因活性产生的下游信号形成了一条通路。然而,这条通路的分子细节目前尚不清楚。已经鉴定出一组对抗苗勒管激素通路功能至关重要的基因。最近,对退化初期的雄性和雌性苗勒管间充质进行的转录组分析已经鉴定出了可能介导苗勒管系统消除的新基因。综合这些证据可用于构建一个初步的基因调控网络,描述苗勒管退化的抗苗勒管激素通路。一个抗苗勒管激素基因调控网络将是研究苗勒管退化、性别分化及其与环境影响关系的有用工具。