PTEN is essential in the maintenance of normal transporter activity in the epididymal epithelium

A fully developed initial segment, the most proximal region of the epididymis, is important for male fertility. Conditional deletion of Pten from the initial segment from postnatal day 17 onwards resulted in de-differentiation of the initial segment. When spermatozoa progressed through the de-differentiated epididymal duct, they developed angled flagella, suggesting compromised sperm maturation, which eventually resulted in male infertility. To understand mechanisms that underlie this sperm maturation defect following loss of Pten, we compared transcriptome profile of the initial segment between controls and knockouts and revealed that the transporter activity was one of the top molecular and cellular functions altered following loss of Pten. Alteration in the protein levels and localization of several transporters following loss of Pten were also observed by immunofluorescence analysis. Epithelial cells of the initial segment from knockouts are more permeable to Fluorescein isothiocyanate-dextran (4000da) compared to controls. When analyzing GEO datasets with Pten deletion in the prostate and inner ear of mice, alteration in transporter activity was also found in these Pten knockout mouse models, suggesting it is a common phenomenon. PTEN regulates transporter activities probably through regulation of cell shape, size, and membrane property, which in turn regulates the intracellular and intercellular micro-environment. 2 groups: PTEN KO vs Control