The key role of growth factors in regulating proliferation and triggering differentiation pathways in gonadal development is now well established (1). Having previously demonstrated the importance of Fgf9 in the mouse (2), we now report the expression of a number of other growth factor receptors implicated in gonadal sex differentiation. Glial cell-line derived neutrotrophic factor (GDNF), epidermal growth factor (EGF), bone morphogenetic protein 4 (BMP4) and nerve growth factor (NGF) have been selected as candidates for study. Expression in vivo for their respective receptors GFRα1, EGFr, BMPr1 and trkA, has been monitored at critical stages from embryonic day (E)13.5 to postnatal day (PN) 25 to address the question whether the receptors are uniformly expressed in both sexes at various timepoints. CBA strain mice were killed humanely according to Schedule 1, and the excised gonads processed for histology and immunocytochemistry (1). Expression of GFRα1 was observed in the ovary only at PN25, limited to the oocyte cytoplasm; however, in the testis, immunostaining in Sertoli cells and spermatogonia at PN7, 15 and 25 was strongly positive. Leydig cells were negative throughout. EGFr showed strong staining in E13.5 and E16.5 testes, but by E18.5 onwards it was only weakly positive with immunostaining for EGFr found in spermatogonia, Sertoli cells, and spermatocytes and Leydig cells at PN7. In the female, weak staining only was seen in embryonic ovaries, although in postnatal stages, the receptor was strongly expressed in oocyte cytoplasm. Expression of BMPr1 was seen in both males and females throughout embryonic development, mostly in somatic cells, as was the expression of trkA. All growth factors may continue to play a proliferative role in the male where spermatogonia are still mitotic in the adult, so it likely that expression of receptors such as GFRα1, observed in the developmental period in this study, will continue throughout life. Staining patterns in the ovary, where expression is mainly restricted to the oocyte, suggest that growth factors may have a more specific functional role other than merely proliferation in the female. In view of this differential expression of growth factor receptors in the two sexes, further work will test these effects of growth factors in vitro where they may be investigated both independently and in potential synergistic combinations.
Life Sciences 2007 (2007) Proc Life Sciences, PC569
Poster Communications: Expression of growth factor receptors at key pre- and postnatal stages of mouse gonadal development
S. Mackay1, T. Alekseeva1, O. Black1, R. A. Smith1
1. Institute of Biomedical & Life Sciences, University of Glasgow, Glasgow, United Kingdom.
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Where applicable, experiments conform with Society ethical requirements.