Copper influence on bank vole's (Myodes glareolus) sexual behavior.

The impact of human activity on the environment has led to a steady increase of the amounts of copper in the ecosystems. This element accumulates in plants and water, potentially exposing rodents to its harmful effects. In industrial districts, a decrease in the density of small rodent populations has been observed. This decline may be caused by many factors, including mortality, decreased fertility, or impaired sexual behavior. The decline in the reproductive abilities of small rodents after copper exposure was demonstrated in our previous work (Miska-Schramm A, Kruczek M, Kapusta J, Ecotoxicology 23:1546-1554, 2014). The aim of the presented research was to determine how copper administered at concentrations similar to those recorded in industrial districts (Cu I-150 mg/kg, Cu II-600 mg/kg, C-control) affects the sexual behavior of small rodents. The model species was the bank vole (Myodes glareolus). The behavior and vocalizations of male-female pairs were recorded during open-field tests: ♂C vs. ♀C; ♂Cu I vs. ♀C; ♂Cu II vs. ♀C while in preference tests, female behavior was assessed in the following combinations: ♀C vs. ♂C & ♂Cu I; ♀C vs. ♂C & ♂Cu II. In the presented work, we show that copper decreased the males' sexual attractiveness. Females showed suppressed preference towards males treated with 600 mg/kg copper. The number of sniffs and a number of approaches towards Cu II males was significantly lower than towards control individuals. Also, in preference test with 150 mg/kg treated animals, total activity was lower towards copper treated animals. At the same time, copper did not influence intra-sexual interactions.

The Effect of Aluminum Exposure on Reproductive Ability in the Bank Vole (Myodes glareolus).

Human impact on the environment is steadily increasing the amounts of aluminum in the ecosystems. This element accumulates in plants and water, potentially exposing herbivores to its harmful effect. In heavily polluted sites, a decrease in the density of small rodent populations has been observed. This decline may be caused by many factors, including decreased fertility. The aim of the presented research was to determine how aluminum, administered at concentrations similar to those recorded in industrial districts (Al I = 3 mg/l, Al II = 200 mg/l), affects the reproductive abilities of small rodents. As the indicators of reproductive abilities, body weight, weight of the testes and accessory sex glands of males, and uterus weight of females were estimated. In females, the number of matured follicles (types 6, 7, and 8) was analyzed, while in males, the quantity and quality (matured, viable, swollen, motile, head abnormalities) of epididymal sperm cells were assessed. Moreover, the development of testes, measured by spermatogenic index, was determined. The model species was the bank vole. Our results have proven that aluminum impairs adult individuals' reproductive abilities by decreasing the quality and quantity of sperm cells and by causing morphologically abnormal development of the gonads. However, no difference in male organometric parameters was found, and only in females treated with 3 mg/l Al, the uterus weight was higher than control. No differences were found in the total number of matured follicles. These results suggest that the decline in rodent numbers in industrial districts is due, at least in part, to poorer males' reproductive abilities, resulting from exposure to aluminum contamination.

Th17 responses are not altered by natural exposure to seasonal allergens in pollen-sensitive patients.

BACKGROUND: Allergic rhinitis affects 10-30 % of the global population and this number is likely to increase in the forthcoming years. Moreover, it commonly co-exists with allergic asthma as a chronic allergic respiratory syndrome. While the involvement of Th2 cells in allergy is well understood, alterations of pro-inflammatory Th17 responses remain poorly characterized. The aim of our study was to determine whether natural seasonal allergen exposure causes changes in T cell subset characteristics in patients with allergic rhinitis and asthma. METHODS: Sixteen patients with allergic rhinitis/atopic asthma (9M, 7F; age 31.8 ± 12.1) and 16 healthy controls were recruited into the study (9M, 7F; age 31.2 ± 5.3). Blood samples were collected from the patients 1-3 months before pollen season (visit 1), within 7 days of the appearance of pollen/initiation of allergic symptoms (visit 2) and 2 weeks after visit 2 following the introduction of symptomatic treatment with antihistamines (visit 3). Flow cytometry was used to assess major T cell subsets (naïve, central memory, effector memory and CD45RA+ effector) and key T cell cytokine production (IFNγ, IL-17A, TNF and IL-4) using intracellular staining. Data were analyzed using repeated measures ANOVA and paired t test. RESULTS: As expected, an increase in the percentage of IL-4+ CD4+ cells was observed during natural pollen exposure in patients with allergic respiratory syndrome. No significant changes were observed in the production of other cytokines, including Th17 cells, which tended to be lower than in the control population but unchanged during pollen exposure. Introduction of antihistamine treatment led to only moderate changes in cytokine production from CD4 and CD8 T cells. Selective changes in CD8+ T cells were observed during natural pollen exposure including a decrease in transient cells (with features of CD45RA+ and CD45RO+ cells) and a decrease in the percentage of central memory cells in the peripheral circulation. Within the CD4 cell group the total percentage of CD45RA positive CD4 cells was increased during pollen exposure. CONCLUSIONS: Th1 and Th17 responses are not altered during pollen season but allergen exposure affects T cell activation and memory cell status in patients with allergic respiratory syndrome.

Effect of copper exposure on reproductive ability in the bank vole (Myodes glareolus).

The amount of copper in natural ecosystems is steadily increasing, due to human activities. It accumulates in plants, posing a threat to herbivores. In polluted areas the population density of small rodents is observed to be lower. The decline in rodent numbers may be caused by increased mortality or diminished fertility. This study examined the effect of copper on the reproductive activity of the bank vole (Myodes glareolus), a small rodent which during foraging often wanders into fields where it might be exposed to pollution. The animals were treated with solutions of 0, 150 or 600 ppm Cu. After 12 weeks of exposure the quality and quantity of the male's sperm was tested. To assess morphological development we compared the experimental groups for body weight, the weight of the male's testes and accessory sex glands, the female's uterus, and the number of matured ovary follicles in tested females. At both doses, copper administration led to lower sperm count and caused sperm head anomalies. The higher dose compromised sperm tail membrane integrity, viability and motility. No effect of copper on morphological development was observed in males, and only the lower dose increased testes weight. In females the higher dose had a negative effect on morphological development, and the lower dose increased uterus weight. No effect of copper on ovarian follicle number was found. For the first time, the morphology of the most typical ovarian follicles of the bank vole is presented.

NADPH oxidases in vascular pathology.

SIGNIFICANCE: Reactive oxygen species (ROS) play a critical role in vascular disease. While there are many possible sources of ROS, nicotinamide adenine dinucleotide phosphate (NADPH) oxidases play a central role. They are a source of "kindling radicals," which affect other enzymes, such as nitric oxide synthase endothelial nitric oxide synthase or xanthine oxidase. This is important, as risk factors for atherosclerosis (hypertension, diabetes, hypercholesterolemia, and smoking) regulate the expression and activity of NADPH oxidases in the vessel wall. RECENT ADVANCES: There are seven isoforms in mammals: Nox1, Nox2, Nox3, Nox4, Nox5, Duox1 and Duox2. Nox1, Nox2, Nox4, and Nox5 are expressed in endothelium, vascular smooth muscle cells, fibroblasts, or perivascular adipocytes. Other homologues have not been found or are expressed at very low levels; their roles have not been established. Nox1/Nox2 promote the development of endothelial dysfunction, hypertension, and inflammation. Nox4 may have a role in protecting the vasculature during stress; however, when its activity is increased, it may be detrimental. Calcium-dependent Nox5 has been implicated in oxidative damage in human atherosclerosis. CRITICAL ISSUES: NADPH oxidase-derived ROS play a role in vascular pathology as well as in the maintenance of normal physiological vascular function. We also discuss recently elucidated mechanisms such as the role of NADPH oxidases in vascular protection, vascular inflammation, pulmonary hypertension, tumor angiogenesis, and central nervous system regulation of vascular function and hypertension. FUTURE DIRECTIONS: Understanding the role of individual oxidases and interactions between homologues in vascular disease is critical for efficient pharmacological regulation of vascular NADPH oxidases in both the laboratory and clinical practice.

Targeting NADPH oxidases in vascular pharmacology.

Oxidative stress is a molecular dysregulation in reactive oxygen species (ROS) metabolism, which plays a key role in the pathogenesis of atherosclerosis, vascular inflammation and endothelial dysfunction. It is characterized by a loss of nitric oxide (NO) bioavailability. Large clinical trials such as HOPE and HPS have not shown a clinical benefit of antioxidant vitamin C or vitamin E treatment, putting into question the role of oxidative stress in cardiovascular disease. A change in the understanding of the molecular nature of oxidative stress has been driven by the results of these trials. Oxidative stress is no longer perceived as a simple imbalance between the production and scavenging of ROS, but as a dysfunction of enzymes involved in ROS production. NADPH oxidases are at the center of these events, underlying the dysfunction of other oxidases including eNOS uncoupling, xanthine oxidase and mitochondrial dysfunction. Thus NADPH oxidases are important therapeutic targets. Indeed, HMG-CoA reductase inhibitors (statins) as well as drugs interfering with the renin-angiotensin-aldosterone system inhibit NADPH oxidase activation and expression. Angiotensin-converting enzyme (ACE) inhibitors, AT1 receptor antagonists (sartans) and aliskiren, as well as spironolactone or eplerenone, have been discussed. Molecular aspects of NADPH oxidase regulation must be considered, while thinking about novel pharmacological targeting of this family of enzymes consisting of several homologs Nox1, Nox2, Nox3, Nox4 and Nox5 in humans. In order to properly design trials of antioxidant therapies, we must develop reliable techniques for the assessment of local and systemic oxidative stress. Classical antioxidants could be combined with novel oxidase inhibitors. In this review, we discuss NADPH oxidase inhibitors such as VAS2870, VAS3947, GK-136901, S17834 or plumbagin. Therefore, our efforts must focus on generating small molecular weight inhibitors of NADPH oxidases, allowing the selective inhibition of dysfunctional NADPH oxidase homologs. This appears to be the most reasonable approach, potentially much more efficient than non-selective scavenging of all ROS by the administration of antioxidants.