Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.
Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.
Curr Top Dev Biol. 2019;134:167-194. doi: 10.1016/bs.ctdb.2019.01.002. Epub 2019 Jan 30.
Primary sex determination is the decision by which the bipotential embryonic gonad commits to either the testicular or ovarian fate. The developing gonad constitutes a unique paradigm for the study of lineage specification, cell fate commitment and the exploration of how distinct cell populations diverge from multipotent progenitors. After the separation of the adreno-gonadal primordium into two distinct primordia, somatic progenitor cells of the gonadal primordium undergo several cell fate decisions and sex-specific cell differentiation. The specification of the supporting and steroidogenic cell lineages into either Sertoli and Leydig cells in the testis, or granulosa and theca cells in the ovary is essential for germ cell development and endocrine function of the gonads. In this review, we focus on the early events leading to gonad formation, including the identity of gonadal progenitors, the genetic networks involved in cell lineage specification, the mutual antagonism of the pro-testis and pro-ovary networks and the importance of timing of developmental events orchestrating testis and ovary development. We discuss, and put into perspective, a number of experiments performed in mice or humans that have shed light on sex-determining mechanisms and, where possible, the clinical significance and limitations of such model organism data.
初级性别决定是指二倍体胚胎性腺决定向睾丸或卵巢命运的过程。正在发育的性腺为谱系特化、细胞命运决定以及探索不同细胞群体如何从多能祖细胞分化而来提供了独特的范例。在肾上腺生殖嵴原基分离为两个不同的原基之后，性腺原基的体祖细胞经历了几个细胞命运决定和性别特异性细胞分化。在睾丸中，支持细胞和类固醇生成细胞谱系特化为支持细胞和间质细胞，而在卵巢中则特化为颗粒细胞和膜细胞，这对于生殖细胞的发育和性腺的内分泌功能至关重要。在这篇综述中，我们重点介绍了导致性腺形成的早期事件，包括性腺祖细胞的特性、参与细胞谱系特化的遗传网络、原睾丸和原卵巢网络的相互拮抗以及协调睾丸和卵巢发育的发育事件时间安排的重要性。我们讨论并从多个角度探讨了在小鼠或人类中进行的一些实验，这些实验揭示了性别决定机制，并且在可能的情况下，探讨了这些模型生物数据的临床意义和局限性。
