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

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.

journal_name

Dev Biol

journal_title

Developmental biology

authors

Matoba S,Hiramatsu R,Kanai-Azuma M,Tsunekawa N,Harikae K,Kawakami H,Kurohmaru M,Kanai Y

doi

10.1016/j.ydbio.2008.09.004

subject

Has Abstract

pub_date

2008-12-01 00:00:00

pages

76-87

issue

1

eissn

0012-1606

issn

1095-564X

pii

S0012-1606(08)01197-4

journal_volume

324

pub_type

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