Hematopoietic prostaglandin D synthase (H-Pgds) is expressed in the early embryonic gonad and participates to the initial nuclear translocation of the SOX9 protein

Dev Dyn. 2011 Oct;240(10):2335-43. doi: 10.1002/dvdy.22726. Epub 2011 Sep 1.

Abstract

In mammals, the Prostaglandin D(2) (PGD(2) ) signaling pathway is involved in male gonadal development, regulating Sox9 gene expression and SOX9 protein subcellular localization through lipocalin prostaglandin D synthase (L-Pgds) activity. Nevertheless, because L-Pgds is downstream of Sox9, its expression cannot explain the initial nuclear translocation of the SOX9 protein. Here, we show that another source of PGD(2) , hematopoietic-Pgds (H-Pgds) enzyme is expressed in somatic and germ cells of the embryonic gonad of both sexes, as early as embryonic day (E) 10.5, before the onset of L-Pgds expression. Inhibition of H-Pgds activity by the specific HQL-79 inhibitor leads to impaired nuclear translocation of SOX9 protein in E11.5 Sertoli cells. Furthermore, analysis of H-Pgds(-/-) male embryonic gonads confirms abnormal subcellular localization of SOX9 protein at the E11.5 early stage of mouse testicular differentiation suggesting a role for H-Pgds-produced PGD(2) in the initial nuclear translocation of SOX9.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / physiology*
  • Animals
  • Cell Nucleus / metabolism
  • Female
  • Gonads / cytology
  • Gonads / embryology*
  • Gonads / metabolism*
  • Humans
  • Intramolecular Oxidoreductases
  • Isomerases / genetics
  • Isomerases / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Prostaglandin D2 / metabolism
  • SOX9 Transcription Factor / genetics
  • SOX9 Transcription Factor / metabolism*
  • Sertoli Cells / cytology
  • Sertoli Cells / metabolism

Substances

  • SOX9 Transcription Factor
  • Isomerases
  • Intramolecular Oxidoreductases
  • HPGDS protein, mouse
  • Prostaglandin D2