Sexual dimorphism is associated not only with somatic and behavioral differences between men and women, but also with physiological differences reflected in organ metabolism. Genes regulated by sex hormones differ in expression in various tissues, which is especially important in the case of liver metabolism, with the liver being a target organ for sex hormones as its cells express estrogen receptors (ERs: ERα, also known as ESR1 or NR3A; ERβ; GPER (G protein-coupled ER, also known as GPR 30)) and the androgen receptor (AR) in both men and women. Differences in sex hormone levels and sex hormone-specific gene expression are mentioned as some of the main variations in causes of the incidence of hepatic diseases; for example, hepatocellular carcinoma (HCC) is more common in men, while women have an increased risk of autoimmune liver disease and show more acute liver failure symptoms in alcoholic liver disease. In non-alcoholic fatty liver disease (NAFLD), the distinction is less pronounced, but increased incidences are suggested among men and postmenopausal women, probably due to an increased tendency towards visceral fat accumulation.

Introduction. The hormone-dependent events that occur throughout the first wave of spermatogenesis, such as the establishment of the number of Sertoli cells (SCs) and spermatogonial stem cells (SSCs) within the seminiferous cords and the setting up of the blood-testis barrier, are important for adult male fertility. Any changes in the T/DHT ratio can result in male subfertility or even infertility. In this study we aimed to evaluate effects of paternal exposure to 5-alpha reductase type 2 inhibitor, finasteride on litter size, androgen levels and germ cell apoptosis in male offspring during postnatal development. Material and methods. The subjects of the study were 7, 14, 21/22, 28, and 90-day-old Wistar male rats (F1:Fin) born from females fertilized by finasteride-treated rats. Offspring born from untreated parental animals were used as a control group (F1:Control). Animals and the collected testes were weighed, blood and intratesticular levels of T and DHT were measured by ELISA, and the apoptotic index of testicular cells was evaluated by TUNEL technique. Results. We observed difficulties in obtaining male newborns from female rats fertilized by finasteride-treated male rats. In the F1:Fin rats, changes in the body and testes weights occurred, and a lower number of apoptotic cells was found during postnatal maturation of the seminiferous epithelium. Changes in androgen concentrations during the first spermatogenesis wave and adult life were also evident. Conclusion. Finasteride treatment of male adult rats may not only cause a decrease in the fertility of parental rats, but also could lead to incorrect, androgen-sensitive course of spermatogenesis in their offspring.

Background: Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver disorders in industrialized Western countries. The prevalence of the disease is estimated to range from 4% to 46% worldwide. The aim of study was to develop an animal model with gradual NAFLD development. Methods: Sprague-Dawley rats were fed a high-fat and high-cholesterol (HFHCh) diet. The rats from the study and control groups were sacrificed after 2, 4, 8, 12, 16, and 20 weeks of dietary exposure. Results: Analysis of biochemical parameters showed that after only two weeks, ALT and cholesterol concentration in serum were elevated. After 4 weeks, TNF-α and HOMA-IR were significantly higher compared to the control group. NAFLD progression started after 12 weeks of diet-weight gain and increased LPS secretions were noticed. During the experiment, rats induced steatosis (from stage 0/1 after 4 weeks to stage 2/3 after 20 weeks), inflammation (from stage 0/1 after 4 weeks to stage 1/2 after 20 weeks), and fibrosis (from stage 1 after 12 weeks to stage 2 after 20 weeks). Conclusion: We can assume that the presented model based on the HFHCh diet induced gradual development of NAFLD. We confirmed that the animal NAFLD model increases LPS secretions during disease progression.

Abstract:The function of testis is under hormonal control and any disturbance of hormonal homeostasis can lead to morphological and physiological changes. Therefore the aim of the study was to investigate the expression of androgen and estrogen receptors (AR, ERs), vanilloid receptor (TRPV1), cytochrome P450 aromatase (P450arom), as well as apoptosis of cells in testis of adult rats chronically treated with letrozole (LT), a non-steroidal aromatase inhibitor, for 6 months. The testicular tissues were fixed in Bouin's fixative and embedded in paraffin. Immunohistochemistry with monoclonal antibodies (abs) against AR, ERa, P450arom, and polyclonal abs against ERb, TRPV1, caspase-3 was applied. Long-lasting estradiol deficiency, as an effect of LT treatment, produced changes in the morphology of testis and altered the expression of the studied receptors in cells of the seminiferous tubules and rate of cell apoptosis. The immunostaining for AR was found in the nuclei of Sertoli cells and the cytoplasm of spermatogonia and spermatocytes in III-IV stages of the seminiferous epithelium cycle. The intensity of staining for P450arom was lower in the testis of LT-treated rats as compared to control animals. The immunofluorescence of ERa and ERb was observed exclusively in the nuclei of Leydig cells of LT-treated rats. There were no changes in localization of TRPV1, however, the intensity of reaction was stronger in germ cells of the seminiferous epithelium after LT treatment. The apoptosis in both groups of animals was observed within the population of spermatocytes and spermatids in II and III stages of the seminiferous epithelium cycle. In testis of LT-treated rats the immunoexpression of caspase-3 was additionally found in the germ cells in I and IV stages, and Sertoli, myoid and Leydig cells. In conclusion, our results underline the important role of letrozole treatment in the proper function of male reproductive system, and additionally demonstrate that hormonal imbalance can produce the morphological abnormalities in testis.

No abstract