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

22Citations
Citations of this article
29Readers
Mendeley users who have this article in their library.

Abstract

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 pre-Sertoli 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. © 2008 Elsevier Inc. All rights reserved.

Cite

CITATION STYLE

APA

Matoba, S., Hiramatsu, R., Kanai-Azuma, M., Tsunekawa, N., Harikae, K., Kawakami, H., … Kanai, Y. (2008). Establishment of testis-specific SOX9 activation requires high-glucose metabolism in mouse sex differentiation. Developmental Biology, 324(1), 76–87. https://doi.org/10.1016/j.ydbio.2008.09.004

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free