Oral Presentation ESA-SRB 2023 in conjunction with ENSA

The Role of Progesterone signalling in Penis Development and Hypospadias (#43)

Luke C Govers 1 , Deidre M Mattiske 1 , Melanie K Stewart 1 , Jay R Black 2 , Darryl L Russell 3 , Andrew J Pask 1
  1. BioSciences, The University of Melbourne, Melbourne, Victoria, Australia
  2. Geography, Earth and Atmospheric science, The University of Melbourne, Melbourne, Victoria, Australia
  3. School of Biomedicine, The University of Adelaide, Adelaide, South Australia, Australia

Hypospadias is the most common persistent congenital abnormality in males affecting 1 in every 125 live male births. Despite this already high incidence, the incidence of hypospadias has been increasing at 1% per annum across Australia and the rest of the world. This rapid increase in the incidence of this problematic phenotype has been largely attributed to the disruption of normal hormonal signalling in the reproductive tract during development, due to our increasing exposure to Endocrine disrupting chemicals (EDCs). Over the last decade we have been investigating how EDCs induce hypospadias and other differences in sexual development (DSDs). However, we still lack fundamental knowledge of the normal balance of hormones which drive male penis development. It has been our aim to address this fundamental gap. Our research has shifted the androgen centric description of penis development to one which focuses on the balance of androgen and oestrogen required to achieve normal penile development. Here we describe another novel role for hormones in penis development. Using micro-CT scanning we have provided the first in depth analyses of the anatomy of the adult penis in the progesterone receptor knockout (PRKO) mouse. We show that males that lack the progesterone receptor (PR) have an increased risk of hypospadias and show other structural abnormalities of the penis. This not only confirms a critical role for progesterone signalling in the penis but implicates this pathway as yet another potential target of endocrine disruption in the increased incidence of male DSDs.