Characterising the genetic profile of gubernacular cells derived from androgen receptor knockout mice (ARKO) during testicular descent

Summary This project will determine the genetic characteristics of the gubernacular cell derived from the androgen receptor knockout mice during the second phase of testicular decent. By creating and maintain cell lines in culture from these mice at the age of embryonic day 17 to day 3 post birth, we will profile the extracellular matrix genes as well as characterise the growth, elongation (mitosis and differentiation) of these cells in vitro.

Project Details

In rodents, the second phrase of testicular descent also known as the androgen dependent phase is completed within the first 2 weeks of neonatal development, whereas in humans this is finalised before birth and the testes move inside the scrotum.    Androgen has been demonstrated to play an important role in remodelling the gubernaculum, however the exact molecular mechanism still remains controversial. While the morphological changes that take place during testicular descent have been previously described, very little is still known about the cellular targets of hormones, genes, signalling pathways and the effects of androgen. There has been two main ways in which AR results in cryptorchidism; 1) by the persistence of the mammary gland tissue in males that were treated with the pharmacological anti-androgen inhibitor which prevented the gubernaculum outgrowth, 2) by stimulating the role of AR-signalling in the genitofemoral nerve releasing calcitonin gene-related peptide (CGRP).    This project will determine the genetic characteristics of the gubernacular cell derived from the androgen receptor knockout mice during the second phase of testicular decent. By creating and maintain cell lines in culture from these mice at the age of embryonic day 17 to day 3 post birth, we will profile the extracellular matrix genes as well as characterise the growth, elongation (mitosis and differentiation) of these cells in vitro. These cells will be compared to adipocytes isolated form the inguinoscrotal fat pad as they are a target tissue for androgen receptors. In addition, by using the CGRP drug we will determine if the molecular signature of the cells can be significantly altered during testicular descent. This study will provide essential evidence between androgen receptor, CGRP, and if we can potential use this as a treatment in children to trigger testicular decent.