Poster Presentation The Annual Scientific Meeting of the Endocrine Society of Australia and the Society for Reproductive Biology 2014

 Prostaglandin D2 synthase mediates male sexual differentiation in the tammar wallaby (#348)

Yu Chen 1 , Hongshi Yu 1 , Andrew Pask 1 , Geoff Shaw 1 , Marilyn Renfree 1
  1. Zoology, Department of Zoology, The University of Melbourne, Melbourne, VIC, Australia

The undifferentiated gonadal primordium has the potential to develop into either a testis or an ovary. The presence of SRY on the Y chromosome triggers SOX9 upregulation which drivestesticular development. SOX9 maintains its own expression by forming two positive feedback loops with FGF9 and prostaglandin D synthase which produces prostaglandin D2 (PGD2), a hormone that reinforces SOX9 expression in Sertoli cells and contributes to the nuclear translocation of SOX9[1].
Sex determination pathways are highly conserved between marsupials and eutherian mammals. However, unlike mice, the relatively long period of marsupial gonadal differentiation as well as their postnatal sexual differentiation offers a convenient model for studying the gonadal differentiation and gene expression. We analysed the transcriptome of developing tammar testes and ovaries and found that PDG2 is significantly upregulated in the testis at the time of gonadal sex determination. We next examined the functional role of PGD2 in developing but indifferent tammar gonads by culturing testes in the presence of a PGD2 synthesis inhibitor HQL-79, while ovaries were treated with exogenous PGD2. After 5 days in culture, gonads were collected for morphological and molecular analysis. Both HQL-79 treated testes and PGD2 treated ovaries showed changes in SOX9 nuclear localization which was impaired in HQL-79 treated testes but in cultured ovaries, exogenous PGD2 induced SOX9 translocation to the nucleus in granulosa cells. Using RT-PCR, the sex determining genes SRY, SOX9, FGF9, AMH, PTGDS and WNT4, were down-regulated in the HQL-79 treated testes treatment, while SOX9 and FOXL2 were slightly increased. HQL-79 treated testes had a thick surface epithelium  while that of PGD2 treated ovaries was thin, These data suggest that prostaglandin D2 plays a fundamental role in the regulation of SOX9 expression and nuclear translocation in marsupials as it does in eutherians. 

  1. Moniot, B., et al., The PGD2 pathway, independently of FGF9, amplifies SOX9 activity in Sertoli cells during male sexual differentiation. Development, 2009. 136(11): p. 1813-21.