RESUMO
Prostate cancer is the most common form of cancer in men, with increased incidence rates observed in older individuals. Prostate cancer is primarily driven via activation of the androgen receptor (AR), the principal transcriptional factor governing prostate cancer cellular programming and its associated metabolism. One of the downstream targets of AR is hepatocyte nuclear factor-1ß (HNF1B), an important oncogenic transcription factor in prostate cancer. In the present study, the regulatory role of HNF1B in enoyl-CoA-(Δ) isomerase 2 (ECI2) expression in the transgenic adenocarcinoma of the mouse prostate (TRAMP) mouse model was investigated. Using this model, tumor progression and associated pathological alterations at 12, 18 and 24 weeks were analyzed. Histological sectioning revealed pathological alterations over time, including thickening of glandular epithelial cells (12 weeks), increases in cellular proliferation (18 weeks), and extensive thickening and hardening of the tissue layer (24 weeks). Expression levels of HNF1B and ECI2 proteins were validated by immunohistochemistry and western blotting at different stages of prostate cancer development. HNF1B and ECI2 exhibited minimal differences in protein expression at 12 weeks in TRAMP+ mice. However, by 18 weeks, TRAMP+ mice exhibited multi-fold increases in HNF1B expression levels, along with downregulation of ECI2. These effects were reversed at 24 weeks, indicating an important time-dependent regulation of gene expression. Taken together, these results demonstrated that upon tumor progression, the initial tumor-protective effect of HNF1B is lost along with downregulated expression of HNF1B and increased expression of ECI2.
RESUMO
We conducted this study to analyze the sperm DNA fragmentation index, conventional semen parameters, blood microelements and seminal plasma reactive oxygen species (ROS) in patients with male infertility to determine the association between each of the above male physiological parameters and DNA fragmentation index and infertility. Eighty cases of infertile males and 20 cases of normal males with children were divided into the infertility and control groups, respectively. Sperm DNA fragmentation index, conventional semen parameters, serum microelement content and seminal plasma ROS levels were detected, and the existing correlation between sperm DNA fragmentation index and the various physiological parameters were studied. The sperm DNA fragmentation index had no correlation with conventional sperm parameters. Our results demonstrated that zinc, lead and magnesium ions in the serum microelements were correlated with sperm DNA fragmentation (p<0.05). Upon an increase in zinc and lead serum concentration, there was a subsequent increase in sperm DNA fragmentation (p=0.008). Furthermore, when magnesium ion increased, it also caused an increase in sperm DNA fragmentation (p<0.05). The seminal plasma ROS of infertile males was higher than that of males with children (p<0.05). Our results suggest that sperm DNA fragmentation index is closely associated with the infertility rate and microelements of serum and seminal plasma ROS can impact the formation of sperm DNA fragmentation. Therefore, the sperm DNA fragmentation index can serve as an important parameter to assess male infertility.