The immunoexpression of androgen receptor, estrogen receptors alpha and beta, vanilloid type 1 receptor and cytochrome p450 aromatase in rats testis chronically treated with letrozole, an aromatase inhibitor

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 polyclonalabs against ERβ, 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 ERα and ERβ 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

Androgen levels and apoptosis in the testis during postnatal development of finasteride-treated male rat offspring

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

The Obscure Effect of Tribulus terrestris Saponins Plus Inulin on Liver Morphology, Liver Fatty Acids, Plasma Glucose, and Lipid Profile in SD Rats with and without Induced Type 2 Diabetes Mellitus

Diabetes is a predictor of nonalcoholic fatty liver disease (NAFLD). There are data suggesting that Tribulus terrestris (TT) saponins act as antidiabetic agents and protect against NAFLD. The effect of saponins may be increased by fermentable fibers such as inulin. The aim of the present study was to investigate the influence of TT saponins and TT saponins plus inulin on the plasma lipid profile and liver fatty acids of rats with induced diabetes mellitus type 2 (T2DM). The study was performed on 36 male Sprague–Dawley rats divided into two main groups: control and diabetic. Animals of the diabetic (DM) group were fed a high-fat diet and injected with streptozotocin (low doses). Animals of the control group (nDM) were on a regular diet and were injected with buffer. After the injections, the animals were split into subgroups: three non-diabetic (nDM): (i) control (c-C); (ii) saponin-treated rats (C-Sap); (iii) rats treated with saponins + inulin (C-Sap + IN), and three diabetic subgroups (DM): (iv) control (c-DM); (v) saponin-treated rats (DM-Sap); (vi) rats treated with saponins + inulin (DM-Sap + IN). Liver fatty acids were extracted and analyzed by gas chromatography, and plasma glucose and lipids were measured. The study showed significant changes in liver morphology, liver fatty acids, plasma lipid profile, and plasma glucose. In summary, supplementation with TT saponins or saponins with inulin for one month decreased the level of steatosis in rats with induced type 2 diabetes. Moreover, there were favorable effects on the plasma lipid profile in the rats. However, additional supplementation with inulin had a negative effect on liver morphology (with a microvesicular type of steatosis) in the non-diabetes group. Moreover, supplementation with inulin had a negative effect on plasma glucose in both diabetic and non-diabetic rats. These data show that a diet enriched with fermentable fibers reveals different effects in different organisms, and not all sources and forms of fiber are beneficial to health

Hormonal (Im)Balance and Reproductive System’s Disorders in Transplant Recipients—A Review

The rising need for treatment of end stage of organ failure results in an increased number of graft recipients yearly. The most commonly transplanted organs are kidney, heart, liver, bone marrow, lung and skin. The procedure of transplantation saves and prolongs the lives of chronically ill patients or at least improves the quality. However, following transplantation recipients must take immunosuppressive drugs on a daily basis. Usually, the immunosuppressive therapy comprises two or three drugs from different groups, as the mechanism of their action varies. Although the benefits of intake of immunosuppressants is undeniable, numerous side effects are associated with them. To different extents, they are neurotoxic, nephrotoxic and may influence the function of the reproductive system. Nowadays, when infertility is an urgent problem even among healthy pairs, transplant recipients face the problem of disturbance in the hypothalamic−pituitary axis. This review will provide an overview of the most common disturbances among the concentration of sex-related hormones in recipients of both sexes at different ages, including sexually immature children, adults of reproductive age as well as elderly women and men. We have also focused on the numerous side effects of immunosuppressive therapy regarding function and morphology of reproductive organs both in males and females. The current review also presents the regimen of immunosuppressive therapy and time since transplantation

The Effect of Chronic Immunosuppressive Regimens Treatment on Aortal Media Morphology and the Balance between Matrix Metalloproteinases (mmp-2 and mmp-9) and Their Inhibitors in the Abdominal Aorta of Rats

Immunosuppressive drugs are widely and chronically used to avoid graft rejection in transplant recipients. However, they are also known to have organotoxic effects and can exert numerous side effects. The aim of this study was to assess whether the chronic treatment of rats with the most commonly used clinical immunosuppressive regimens in organ recipients had an effect on the morphology and function of the aorta. The rats were divided into five groups and each group was chronically treated with different sets of three immunosuppressive drugs (TRG, CRG, MRG, CMG, TMG) for 6 months. The changes were most profound in calcineurin inhibitor-based protocols. TMG protocol treatment was characterized by the most numerous alterations such as morphological changes, changes in the thickness of the tunic media, wider distances between elastic lamellae, an increase in the number of vSMCs and changes in collagen deposition. We concluded that the morphological changes were connected with MMP-2 and MMP-9/TIMP-2 and TIMP-1 imbalances, which was also determined and noticed

The Interplay between Finasteride-Induced Androgen Imbalance, Endoplasmic Reticulum Stress, Oxidative Stress, and Liver Disorders in Paternal and Filial Generation

Finasteride (Fin) causes androgen imbalance by inhibiting the conversion of testosterone (T) to its more active metabolite, dihydrotestosterone (DHT). Androgen receptors (AR) are present (e.g., in hepatocytes), which have well-developed endoplasmic reticulum (ERet). Cellular protein quality control is carried out by ERet in two paths: (i) unfolded protein response (UPR) and/or (ii) endoplasmic reticulum associated degradation (ERAD). ERet under continuous stress can generate changes in the UPR and can direct the cell on the pathway of life or death. It has been demonstrated that genes involved in ERet stress are among the genes controlled by androgens in some tissues. Oxidative stress is also one of the factors affecting the functions of ERet and androgens are one of the regulators of antioxidant enzyme activity. In this paper, we discuss/analyze a possible relationship between androgen imbalance in paternal generation with ERet stress and liver disorders in both paternal and filial generation. In our rat model, hyperglycemia and subsequent higher accumulation of hepatic glycogen were observed in all filial generation obtained from females fertilized by Fin-treated males (F1:Fin). Importantly, genes encoding enzymes involved in glucose and glycogen metabolism have been previously recognized among UPR targets

Modulatory effect of inulin with soya isoflavones on plasma lipid profile and liver SCD-18 index in rats with induced type-2 diabetes mellitus

Obesity and type-2 diabetes are often associated with nonalcoholic fatty liver disease (NAFLD). Soya isoflavones act as antidiabetic agents and protect against NAFLD. There are data suggesting that inulin may increase the plasma concentration and effect of soya isoflavones. The aim of the present study was to compare the effect of soya isoflavones, as opposed to the effect of soya isoflavones with inulin, on plasma lipid profile, liver morphology, and liver fatty acids in rats with induced type-2 diabetes mellitus. Data were collected on thirty-six male Sprague- Dawley rats divided into control and diabetic groups. Animals in the diabetic (DM) group were on a high-fat diet and were injected with low doses of streptozotocin. Animals in the control groups were fed a regular diet and were injected with a buffer. After the injections, the animals were divided into three groups of nondiabetic rats (nDM)-controls (c-nDM), rats treated with isoflavones (IS-nDM), and rats treated with isoflavones plus inulin (IS+IN-nDM)-and three parallel diabetic (DM) subgroups: controls (c-DM), rats treated with isoflavone (IS-DM), and rats treated with isoflavones plus inulin (IS+IN-DM). Hepatic steatosis and fibrosis were examined using hematoxylin-eosin staining and Mallory’s trichrome methods respectively. Liver fatty acids were extracted and analyzed by gas chromatography. A lipid blood test was performed. The study showed significant changes in liver fatty acids, liver morphology, and plasma lipid profile. The estimated SCD-18 index significantly decreased in both the control and DM groups after isoflavone supplementation. The level of liver steatosis and fibrosis also decreased after isoflavone supplementation in the DM groups. The plasma lipid profile showed increased levels of HDL-C after isoflavone supplementation in the DM groups. These results support the protective use of isoflavones in liver steatosis and as beneficial to plasma lipid profile in individuals with diabetes. A novelty of this work is its comparison of supplementation using soya isoflavones with supplementation using both soya isoflavones and inulin. Surprisingly, additional supplementation with inulin modulates the positive effect of isoflavone