Antioxidant enzyme expression of mRNA and protein in the epididymis of finasteride-treated male rat offspring during postnatal development

Abstract

A b s t r a c tIntroduction: We verify whether finasteride had a transgenerational effect on the epididymal expression of antioxidant enzymes, and the correlation between these enzymes and blood androgen concentrations in male offspring (F1:Fin) of females fertilized by finasteride-treated male rats. Material and methods: The expression of CAT, SOD1, GPX5, GR on the mRNA and protein levels was evaluated in the epididymis at postnatal day (PND) 7, 14, 21, 28 and 90. Levels of T and DHT were correlated with mRNA levels of enzymes by Spearman's rank correlation coefficient. Results: A change in the levels of transcripts was noted in F1:Fin rats: CAT decreased at PND 28 (p < 0.01) and increased at PND 90 (p < 0.01); SOD1 increased at PND 7 (p < 0.0001), 21 (p < 0.001), 90 (p < 0.0001) and decreased at 14 PND (p < 0.01); GPX5 increased at PND 14 and 21 (p < 0.0001); GR decreased at PND 21 and 28 (p < 0.0001). Altered immunolocalization of enzymes within the epididymal epithelium was observed. Negative correlations between GPX5 mRNA with androgens (T, p = 0.0002; DHT, p = 0.0009) were visible in the control rats, and positive correlation between DHT and CAT mRNA (p = 0.03), in opposite to F1:Fin group were was negative for both androgens (T, p = 0.044 and DHT, p = 0.02). Conclusions: Finasteride treatment of adult male rats may cause changes in antioxidant defense system in the epididymis of their offspring, leading to improper ROS concentrations that can affect post-testicular sperm maturation.

The Postnatal Offspring of Finasteride-Treated Male Rats Shows Hyperglycaemia, Elevated Hepatic Glycogen Storage and Altered GLUT2, IR, and AR Expression in the Liver

“…In our previous reports [ 32 , 33 ] conducting on the same experimental model we showed that, the male rats from F1:Fin group were characterized by a differing serum testosterone and dihydrotestosterone concentration in comparison to the F1:Control.…”

“…However this mechanism will be in the future evaluated by us (see Appendix A ). The observed overweight could have been also associated with the modulation of adipose tissue metabolism by androgens (mainly DHT), as indicated by microarrays analysis by Zhang et al [ 45 ], and therefore could be the result of a changed T–DHT ratio [ 33 ].…”

“…The procedure of measurement of T and DHT in blood serum is the same as in our previously published work [ 33 ]. A standard sandwich ELISA assay was performed on the serum using a rat specific T and DHT ImmunoAssay System kit (CUSABIO; CBS-E05100r and CBS-E07879r), according to the manufacturer’s instructions, and an Asys UVM 340 microplate reader (Asys Hitech Gmbh, Austria).…”

“…A probability of p ≤ 0.05 was considered statistically significant. Additionally, the serum levels of T and DHT, presented in our previous study [ 33 ], were correlated with the levels of GLUT-2, IR, and AR transcripts by Spearman’s rank correlation coefficient ( r s ). The same test was used to correlate serum glucose concentration with age of animals and hepatic GLUT-2 mRNA.…”

“…In our previous study on the same animal model, we showed that the offspring (F1:Fin) of rats exposed to finasteride had altered levels of serum androgens (T, DHT) and adverse changes in the morphology and physiology of testes and epididymides [ 32 , 33 ]. Given this trans-generational effect of finasteride on the male reproductive system and the aforementioned information on the role of androgens and AR in glucose metabolism, the aim of this study was to assess whether the androgen (T, DHT) imbalance in the F1:Fin generation of rats from males receiving finasteride can affect the accumulation of glycogen in the liver (androgen-dependent organ), serum glucose concentration and the hepatic mRNAs and proteins, GLUT2, IR, and AR expression.…”