Research under the supervision of Dr. Barry T. Hinton of the Department of Cell Biology at the University of Virginia Health Systems
Summer Session III 2012
It is very clear that the epididymis plays a crucial role in the maturation of spermatozoa and without a fully developed and functional epididymis male infertility will result. We are especially interested in understanding the mechanisms that regulate the development of this important organ because disruptions to epididymal function will also arise as a consequence of abnormal development. Very little is known either of the process of epididymal development or the nature and causes of congenital defects that lead to male infertility. A major event during Wolffian/epididymal duct embryonic development is elongation and coiling. It is hypothesized that elongation is the result of cell proliferation coupled with directed cell rearrangements, Coiling is regulated by the planar cell polarity signaling pathway (PCP). PTK7 is a major regulator of non-canonical PCP pathway. Our previous study discovered that mice are null for Ptk7 have a shortened epididymal duct and an unusually coiling pattern compared to wild type duct at the same age. In this study we indicated the epithelial and mesenchymal cells in the PTK7 knockout epidymides were less organized compared to the control. Although the basal to apical polarity of epithelial cells and the formation of extracellular matrix (ECM) at the base of epithelium did not impaired by PTK7 ablation, the myosin II activity was affected in the surrounding mesenchymal cells of epididymal duct after loss of PTK7 in the epididymis. In addition, at E18.5 coiling is proceeding in a proximal to distal manner, with more coiling activity in the proximal region and less activity in the distal region. Interestingly, myosin II activity in the surrounding mesenchymal cells was correlated with the coiling activity in the different epidymal regions, implicating the role of myosin contractility in the regulation of epididymal duct coiling. Taken together, we hypothesized that PTK7 regulates epididymal duct coiling through regulating myosin II activity in the surrounding mesenchymal cells of the duct. Introduction and Theory
It is well defined that the epididymis participates in an important responsibility in the maturation of spermatozoa and without a fully developed and functional epididymis male infertility will result. It has become our utmost concern to study and understand the mechanisms that regulate the development of this important organ because disruptions to the epididymal function may also arise as a consequence of abnormal development. Very little is known of the process of epididymal development or the causes of congenital defects that lead to male infertility. Without proper development of the initial segment of the epididymis can lead to infertility. Along with other various essential parts of the male fertile system, any abnormalities are sure to cause a disruption in the process of sperm maturation. Therefore it is essential that epididymal abnormalities be detected during the stages of male infertility. The Epididymis develops from the anterior part of the Wolffian duct. A major event during the Wolffian-Epididymal duct development is elongation and coiling. Remarkably, the mouse epididymis elongates from 1mm at embryonic day 14.5 to 1.2mm in the adult whereas the human epididymis elongates to 6m. Although elongation and coiling is not a trivial event, so far little is known concerning the molecular mechanism that regulates this event. It is well established that during development, epididymal cells are highly proliferative (reff). Presumably cell proliferation is a major contributor to epididymal elongation and coiling. However additional mechanism must also...