The postnatal offspring of finasteride-treated male rats show altered ERα and PCNA expression in the liver

Abstract

A growing body of data indicates that the physiology of the liver is sex-hormone dependent, with some types of liver failure occurring more frequently in males, and some in females. In males, in physiological conditions, estrogens acts via estrogen receptors (ERs). Estrogen may promote liver tumorigenesis, due to the increased hepatocyte mitogenic activity or may cause regression of hypertrophic liver nodules or, as in the case of hepatic adenocarcinoma, may reduce the estrogen-binding ability of hepatocytes. In our previous studies, we demonstrated biochemical changes in blood parameters as well as physiological and morphological changes in the liver of male rats from the paternal generation receiving finasteride. Therefore, the goal of the study was to assess whether the administration of finasteride has an intergenerational effect on ERα and PCNA (to detect mitotic activity) expression in the hepatocytes of male rat offspring. The study was conducted on the liver from immature (7, 14, 21, 28 days age) and mature (90 days age) Wistar male rats (F1:Fin) born by females fertilized by finasteride-treated rats. The control group was the offspring (F1:Control) of untreated Wistar parents. After the IHC reaction, the slides were undergoing Quantitative Computer Image Analysis. We demonstrated an altered pattern of immunoexpression level of the studied markers in the F1:Control vs F1:Fin groups. We noticed a positive (F1:Control 7PND, postnatal days) and negative (F1:Control 90PND) correlation between ERα and PCNA immunoexpression. Additionally, the expression of ERα and PCNA was examined at the mRNA level. This paper is documenting that finasteride use by paternal generation males (in reproductive age) may lead to an intergenerational effect detrimental to the liver function of their male offspring.