06-P031 Development of the male reproductive system: Potential mediators of androgen action during the male programming window

By E16.5, the secondary lens fibre cells were abnormally arranged with poor lens suture formation. Apoptotic cells were found in the centre of the lens as shown by TUNEL assay, the cytoskeleton and cell adhesion in the lens centre were disturbed as shown in immunohistochemistry analysis. By western blotting we found that mutant c-crystallins were reduced in amount and enriched in the insoluble fraction, suggesting that mutant ca-crystallins were misfolded and protein aggregates were formed. We found that the expression of genes involved in the unfolded protein response (UPR) pathways including BiP, CHOP and spliced variant of XBP-1 were all up-regulated significantly in E14.5 and 16.5 mutant lenses. Therefore, the mutant cA-crystallin appeared to trigger UPR and cell death in the fibre cells. The mutant cells lost their normal cell adhesion, failed to maintain the proper lens architecture, leading to cataract formation.