Establishment of testis-specific SOX9 activation requires high-glucose metabolism in mouse sex differentiation

作者：Matoba Shogo; Hiramatsu Ryuji; Kanai Azuma Masami; Tsunekawa Haoki; Harikae Kyoko; Kawakami Hayato; Kurohmaru Masamichi; Kanai Yoshiakira^*

来源：Developmental Biology, 2008, 324(1): 76-87.

DOI：10.1016/j.ydbio.2008.09.004

• Glycogen
• Energy metabolism
• SOX9
• pre-Sertoli cell
• Gonad
• Sex differentiation
• Mouse

In mouse sex differentiation, SRY Promotes Sertoli cell differentiation via SOX9 action, resulting in testis formation. SRY/SOX9 also initiates various testis-specific morphogenic events including glycogenesis in preSertoli cells, suggesting the importance of glucose storage for certain SRY/SOX9-downstream events in gonadal sex determination. However, it remains unclear which cell types and what molecular/cellular events require sex-dimorphic high-energy metabolic rate. Here we show that the establishment of SOX9 activation itself is a metabolically active process with sex-dimorphic high-energy requirements in gonadal sex differentiation. The glucose-deprivation and metabolic rescue experiments using genital ridge cultures of the XY/XX-wildtype and XX/Sry transgenic embryos demonstrated that, among the various somatic cell types, pre-Sertoli cells are the most sensitive to glucose starvation despite the differences between XX/Sry and XY genotypes. Moreover, our data showed that, in developing pre-Sertoli cells, the high-glucose metabolic state is required for the establishment of SOX9 expression through an ECM (extracellular matrix)-mediated feed-forward pathway. In contrast, the expression of SRY, SF1/Ad4Bp, GATA4 and WT1, as well as initiation of early SOX9 expression, is properly maintained in the glucose-deprived condition. Therefore, our results imply the metabolic importance of the high-glucose condition for the establishment of SOX9 activation in testis differentiation.

• 出版日期2008-12