The Joint Annual Scientific Meetings of the Endocrine Society of Australia and the Society for Reproductive Biology 2018

Sexually dimorphic requirement for FGFR2 expression in testicular and ovarian development (#305)

Anthony D Bird 1 , Dagmar Wilhelm 2 , Liang Zhao 3 , Stefan Bagheri-Fam 2 , Janelle M Ryan 1 , Peter Koopman 3 , Vincent R Harley 1 , Brittany Croft 1
  1. Hudson Institute of Medical Research, Clayton, VIC, Australia
  2. Department of Anatomy and Neuroscience, The University of Melbourne, Melbourne, VIC, Australia
  3. Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia

In mice, male sex determination in XY gonads critically depends on sufficient SOX9 expression in the supporting cell population, which drives differentiation of Sertoli cells at ~11.5 days post coitum (dpc). This largely relies on FGF9-FGFR2 mediated repression of pro-ovarian signalling pathways such as WNT4/RSPO1 and FOXL2, which inhibit SOX9. Since Sertoli cell identity in adult testes is reversible and retains potential for trans-differentiation into ovarian granulosa cells, we first asked whether FGF9-FGFR2 signalling is involved in Sertoli cell maintenance throughout testicular development. To investigate this, Fgfr2 was deleted in the Sertoli cells of XY gonads after the stage of sex determination at 12.5 dpc using Fgfr2fl/flmice mated to the Amh-Cre deleter line. Surprisingly, we found that testicular development, as well as spermatogenesis was normal in XY Fgfr2fl/fl; Amh-Cre mice up to 5 months of age. To support this, examination of FGFR2 localisation in XX and XY gonads at 11.5-13.5 dpc revealed that after 11.5 dpc (where robust somatic and germ cell expression is observed), FGFR2 expression in 12.5-13.5 dpc XY gonads is almost absent in somatic cells and largely restricted to germ cells. In contrast 12.5-13.5 dpc XX gonads showed strong FGFR2 expression in somatic cells but minimal expression in germ cells. To investigate the unexplored role of FGFR2 in the developing ovary we then examined XX Fgfr2c-/- gonads. Although differentiation of FOXL2-positive granulosa cells was normal at all stages examined, MVH-positive germ cell numbers were severely reduced after 11.5 dpc and were often not detected at 15.5 dpc. Together, these results suggest that FGFR2 expression in Sertoli cells is dispensable for testicular development after the stage of sex determination at 11.5-12.0 dpc, while FGFR2 expression is required in the somatic cell population of the ovary beyond 12.5 dpc for germ cell maintenance.