Paternal finasteride exposure and its impact on offspring testicular histopathology and intracellular junctions: the role of occludin and N-cadherin.

The clinical history of newborns usually does not include the information about the medications taken by their fathers before /during conception that could cause a hormonal imbalance in the father. The aim of this study was to perform a histopathological analysis of testicular changes, with a main focus on changes in cell junctions, supported by gene expression analysis (microarrays) and protein analysis (IHC, immunohistochemistry). The F1:Fin consisted of the offspring of paternal rats treated with finasteride. The F1:Control consisted of the offspring from untreated male rats. Testes were collected on postnatal days 7, 14, 21, 28 and 90. H&E staining was used to assess testis histology. IHC reactions and microarray analysis were performed to assess expression of occludin and N-cadherin. Many histological changes were observed in the testes of all experimental groups, including irregularity and folding of the seminiferous tubule (ST) wall, ingrowth of one ST into another, reduced tubular diameter, vacuolation in the seminiferous epithelium (SE), excessive proliferation of germ cells, sloughing of immature germ cells into the lumen of STs, multinucleated giant cells in the SE and Leydig cells with abnormal morphology. A significantly higher number of abnormal tubules were found in F1:Fin. The digital image analysis showed significant changes in the occludin and N-cadherin immunoexpression. Microarray analysis revealed changes in expression of these proteins. Finasteride administered to the paternal rats before and during the mating period may contribute to histopathological changes in the SE, STs wall or interstitial tissue leading to disturbances in the testicular physiology of the male offspring.