Function Of Testicular Tissue Research Articles

Hypothyroidism and Fertility: An Animal Model follows up in The Second-Generation.

Objective Hypothyroidism is known as the most common endocrine disorder. The prevalence of hypothyroidism in the female and male population is 2% and 0.2%, respectively. Maternal hypothyroidism is a defect in the thyroid hormones transition from the mother to the fetus. The present study was conducted to find whether maternal hypothyroidism affects the fertility of the second generation. Materials and Methods In this experimental study, twelve adult female rats weighting 180-220 g were randomly divided into case and control groups. Hypothyroidism was induced by dissolving 0.1 g/L of 6-n-propyl-2-thiouracil in drinking water toward the end of pregnancy and lactation. At the end of the breastfeeding period, the blood samples of female children were collected. Six healthy, mature, female rats were selected and kept until they reached maturity, and were then mated with male rats. After observing the female rats’ delivery, blood samples were collected from their male and female newborns and the healthy rats were selected. Results There was a significant difference in the volume and size of ovarian as well as in the number of secondary follicles in comparison with the control group (P=0.025). However, there were no significant changes in the other parameters including the number of primary follicles, the number of Graafian follicles and sperm parameters. There was no significant decrease in the testicular volume and size, number of Leydig cells and seminiferous tubules diameter. ConclusionMaternal hypothyroidism has no significant effects on testicular tissue function, and sperm parameters in the second generation, but can significantly reduce the rate of secondary follicles in the second generation female rats.

Lepidium draba L. leaves extract ameliorated cyclophosphamide-induced testicular toxicity by modulation of ROS-dependent Keap1/Nrf2/HO1, Bax/Bcl2/p53/caspase-3, and inflammatory signaling pathways.

The aim of this study was to evaluate the protective effects of Lepidium draba L. extract on cyclophosphamide (CP)-induced oxidative damages to testes in rats using sex hormones, antioxidant properties, inflammatory, and apoptotic pathways. Six groups of male Wistar rats (n=6/group) received distilled water (NC), CP (100mgkg-1 day-1 /intraperitoneal), CP with L. draba extract [100 (LDCP 100), 200 (LDCP 200), and 400 (LDCP 400) mg/kg/day/orally] and also only L. draba extract [400 (LD400) mg/kg/day/orally] in 35days. On day 36 of the study, sperm parameters, serum levels of sex hormones, antioxidant enzyme activity, nitric oxide levels, and inflammatory cytokines and also testicular tissue (ferric reducing antioxidant power and thiobarbituric acid reactive substances levels and expression of ROS-dependent pro/anti-apoptotic pathways) were evaluated. In L. draba-treated groups, especially doses of 200 and 400, in addition to improving sperm parameters and sex hormones (Increased levels of all three hormones luteinizing hormone, follicle-stimulating hormone, and testosterone), serum antioxidant (catalase, superoxide dismutase, and glutathione peroxidase activity increased and nitric oxide levels decreased), and anti-inflammatory properties (levels of IL-6, TNF-α, and IL-1β decreased and MIF and TGF-β increased) also showed modification. By strengthening the anti-apoptotic pathway of Keap1/Nrf2/HO1 and inhibiting the apoptotic pathway of Bax/Bcl2/p53/caspase-3, L. draba maintains the structure and function of testicular tissue so that eventually p53-positive testicular cells are reduced and Bcl-2-positive cells increased. L. draba can help to maintain sexual potency and fertility in patients undergoing chemotherapy by controlling their apoptotic, anti-inflammatory, and antioxidant pathways. PRACTICAL APPLICATIONS: Lepidium draba have considerable antioxidant properties and can help to maintain sexual potency and fertility in patients undergoing chemotherapy by controlling their apoptotic, anti-inflammatory, and antioxidant pathways. The present results are useful to find a suitable supplement for improving the sexual performance of patients treated with chemotherapy drugs.

Cholestasis Alters miR-34c-5p Expression in the Testes of Male Wistar Rats

Background: Cholestasis is a pathophysiological condition, significantly reducing spermatozoa production. MiR-34c is highly expressed in adult male testicles and controls different stages of spermatogenesis. Objectives: Here, we aimed to investigate miR-34c expression in the testes of rat models of cholestasis. The expressions of THY-1, FGF-2, and CASP-3 genes, that are targeted by mirR-34c were also investigated. Methods: Cholestasis was induced in six adult rats via bile duct ligation. Four weeks after cholestasis induction, sera and testicular tissues were collected for further examinations. The levels of liver enzymes were measured using the ELISA. The structure of the testes was evaluated by histological examination. Total RNA was extracted from testes using a special kit and converted to cDNA. The expressions of miR-34c-5p, THY-1, FGF-2, and CASP-3 genes were determined by Real-Time PCR. Results: The serum levels of ALP, AST, and ALT were significantly elevated in the rat models of cholestasis (P < 0.001). Real-Time PCR revealed that the expressions of miR-34c-5p, THY-1, and FGF-2 genes decreased while CASP-3 gene was upregulated in the testes of cholestatic animals (all differences were significant at P < 0.05). Conclusions: Our study indicated that cholestasis was associated with reduced expression of miR-34c and altered expression of its target genes in the testis. Our results highlight the potential effects of cholestasis, a hepatobiliary disease, on testicular tissue function and male fertility.

Bisamide Derivative of Dicarboxylic Acid Contributes to Restoration of Testicular Tissue Function and Influences Spermatogonial Stem Cells in Metabolic Disorders.

Metabolic syndrome can lead to several challenging complications including degeneration of the pancreas and hypogonadism. Recently, we have shown that Bisamide Derivative of Dicarboxylic Acid (BDDA) can contribute to pancreatic restoration in mice with metabolic disorders via its positive effects on lipid and glucose metabolism, and by increasing the numbers of pancreatic stem cells. In the present study, we hypothesized that BDDA might also be effective in restoring hypogonadism caused by metabolic syndrome. Experiments were performed on male C57BL/6 mice with hypogonadism, where metabolic disorders have been introduced by a combination of streptozotocin treatment and high fat diet. Using a combination of histological and biochemical methods along with a flow cytometric analysis of stem and progenitor cell markers, we evaluated the biological effects of BDDA on testicular tissue, germ cells, spermatogonial stem cells in vitro and in vivo, as well as on fertility. We demonstrate that in mice with metabolic disorders, BDDA has positive effects on spermatogenesis and restores fertility. We also show that BDDA exerts its therapeutic effects by reducing inflammation and by modulating spermatogonial stem cells. Thus, our results suggest that BDDA could represent a promising lead compound for the development of novel therapeutics able to stimulate regeneration of the testicular tissue and to restore fertility in hypogonadism resulting from complications of metabolic syndrome.

Investigation of the Protective Effects of Amlodipine on the Structure and Function of Testicular Tissue following Experimental Unilateral Cryptorchidism in Rats

Objective- Cryptorchidism, common birth defect of the male genital tract, is one of the causes of fertility problems. The elevation of tissue temperature following of cryptorchidism could induce oxidative stress which influences the cellular and tissue degeneration. Amlodipine is a third-generation of calcium channel blockers which has antioxidant activity. The aim of this study was to evaluate the protective effects of amlodipine on testicular tissue alterations in an animal model of cryptorchidism. Design- Experimental study Animals- Thirty adult male Sprague-Dawley rats weighing 200-220g Procedure- Experimental cryptorchidism was induced in adult rats. Amlodipine (10 mg/kg b.w.) was administrated orally for two and four consecutive weeks. The experimental groups consisted of non-treated cryptorchidism (n=10) and treated cryptorchidism (n=10) groups. Testicular tissue samples were collected on days 14 and 28 following of cryptorchidism form non-treated and treated groups. Histopathological and morphometrical studies with the evaluation of microscopic indices of spermatogenesis were prepared on tissue samples. Results- Tubular atrophy with germinal epithelium disarrangement was observed in cryptorchidism groups. These changes were reduced dose-dependently in treated animals. The mean of Sertoli cells was reduced significantly (p=0.025) in four weeks non-treated and the mean of germ cells lineage was reduced significantly (p<0.0001) in four weeks non-treated and two weeks treated cryptorchidism groups compared to the control group. Similarly, all microscopic indices of spermatogenesis were reduced following the induction of cryptorchidism. These alterations were reduced time-dependently in amlodipine treated groups. Conclusion and clinical relevance- The results of this study revealed that the administration of amlodipine as an antioxidant agent, time-dependently could be effective on the reduction of cellular and tissue damages of testicular tissue induced by cryptorchidism. It seems some parts of these protective effects may be done through its activity as calcium blocker which declines apoptotic processes by reduction of cytoplasmic calcium levels.

Polycyclic Aromatic Hydrocarbons and Endocrine Disruption: Role of Testicular Gap Junctional Intercellular Communication and Connexins.

Ambient air pollution and smoking are well-documented risk factors for male infertility. Prevalent air pollutants and cigarette smoke components, polycyclic aromatic hydrocarbons (PAHs), are environmental and occupational toxicants that act as chemicals disrupting endocrine regulation and reproductive potential in males. Testicular gap junctional intercellular communication (GJIC) is critical for normal development and function of testicular tissue, thus we assessed GJIC as a process potentially targeted by PAHs in testes. Lower MW PAHs with a bay or bay-like region rapidly dysregulated GJIC in Leydig TM3 cells by relocalization of major testicular gap junctional protein connexin 43 (Cx43) from plasma membrane to cytoplasm. This was associated with colocalization between Cx43 and ubiquitin in intracellular compartments, but without any effect on Cx43 degradation rate or steady-state Cx43 mRNA levels. A longer exposure to active PAHs decreased steady-state levels of full-length Cx43 protein and its 2 N-truncated isoforms. Inhibition of GJIC by PAHs, similarly to a prototypic GJIC-inhibitor TPA, was mediated via the MAP kinase-Erk1/2 and PKC pathways. Polycyclic aromatic hydrocarbon-induced GJIC dysregulation in testes was cell-type-specific because neither PAH dysregulated GJIC in Sertoli TM4 cells, despite PAHs were rapidly taken up by both Leydig TM3 as well as Sertoli TM4 cells. Because TPA effectively dysregulated GJIC in both testicular cell types, a unique regulator of GJIC targeted by PAHs might exist in Leydig TM3 cells. Our results indicate that PAHs could be a potential etiological agent contributing to reproductive dysfunctions in males through an impairment of testicular GJIC and junctional and/or nonjunctional functions of Cx43.

The ultrastructural changes of the sertoli and leydig cells following streptozotocin induced diabetes.

This investigation was conducted to evaluate the effects of diabetes on the structure and function of testicular tissue. Diabetes was induced in male adult rats by a single intraperitoneal injection of streptozotocin. Body and testicular weight, hormonal analyses, histological and ultrastructural analyses were measured. The body and testicular weights were dropped significantly (P< 0.05) in diabetic rats in comparison with control rats. On the other hand, in diabetic rats, the blood glucose level increased significantly (P< 0.05). The blood plasma levels of testosterone, 17-β estradiol, progesterone, FSH and LH were reduced in diabetic rats. Histomorphological studies were revealed reduction in diameter of seminiferous tubules and germinal epithelium height, edema in interstitial tissue, germ cell depletion, decrease in cellular population and activity with disruption of spermatogenesis in diabetic rats. Ultrastructural study showed the mitochondrial change and reduction of smooth endoplasmic reticulum in Sertoli and presence of lipid droplets in Leydig cells of diabetic rat's testes. The results of the present study confirmed that, the ultrastructural changes of Sertoli and Leydig cells, brought about by streptozotocin induced diabetes, because of the alterations in pituitary gonadotropins, and these changes influence the normal spermatogenesis in rats.

Inhibin B in the assessment of seminiferous tubular function.

Inhibin B is a testicular hormone that regulates follicle-stimulating hormone secretion in a negative feedback loop. In males, the serum level of inhibin B is detectable throughout life, with a prominent change in the first year of life and during puberty, reflecting the testicular response to the activity of the hypothalamic-pituitary-gonadal hormone axis. During childhood, the basal serum inhibin B level is a direct marker of the presence and function of testicular tissue that has proved useful in the diagnosis of patients with cryptorchidism or ambiguous genitalia. In adult men, the inhibin B level is closely related to spermatogenesis. Measurements of serum inhibin B may provide valuable clues for the differential diagnosis of male infertility. A further exploration of the relationship between inhibin B, Sertoli cell function and spermatogenesis will improve the usefulness of inhibin B as a tool in the investigation of male reproductive health.