In utereo androgen administration Induces changes in gene expression and purkinje cell development of the cerebellum
  Steroids play a major role in the development of the CNS with those brain areas involved in sexual behaviour having been the focus of most neuroendocrine studies to date e.g. the hypothalamus and pituitary gland (Feist and Schreck, 1996; Mong, et al., 1999; Toran-Allerand, et al., 1980). This occurs via intracellular and cell-surface receptors that regulate changes in protein synthesis (Mensah-Nyagan, et al., 1999) to modify events related to neuronal survival and synapse formation (Breedlove, 1992).
Many steroidogenesis-associated enzymes have been described in the cerebellum and cortex, but the impact of steroids on their development has yet to be investigated. A steroidal fetal programming model was utilised to investigate how gene expression in these two brain regions is affected by steroid exposure during development, and examine how this may lead to a change in brain architecture and function.
The main aims of this study were to identify changes in the cerebellar expression of genetic markers of steroid metabolism, using quantitative real-time polymerase chain reaction (qRT-PCR), that result from exposure to testosterone propionate (TP) during development in male sheep. The cerebellum follows a clear developmental trajectory and contains an established cytoarchitecture that enabled us to readily identify the effects of TP treatment on the developing brain by utilising histological analyses. Further alterations of gene expression in the developing male ovine cortex were also identified using microarray analysis. The results provide novel findings in regards to androgen-sensitive gene expression in the developing ovine cerebellum and cortex but perhaps the most striking result was that androgen over-exposure delays cerebellar development, which may have consequences in later life on motor and/or cognitive function.

  • Dates:

    2011 to 2015

  • Qualification:

    Doctorate (PhD)

Project Team