Effects Of SO₂ And Arsenic Exposure On Respiratory Tract And Male Reproduction In Mice

Sulfur dioxide?SO₂?is a ubiquitous gaseous pollutant that is emitted mainly from the burning of sulfur-containing fossil fuels.Because a coal dominated energy structure is difficult to be completely replaced in the short term,coupled with the increased use of scattered coal in northern area in recent years,SO₂ pollution remains serious in our country.Researchers have demonstrated that SO₂ can weaken or destroy immune defenses of respiratory system and induce many respiratory inflammatory diseases.As a chronic respiratory disease featured with inflammation and immune system disorder,asthma is increasingly prevalent and has become a global health issue.Chronic asthma-induced hypoxia may also lead to cell apoptosis in testis tissue and further affect male reproduction.SO₂ is one of the risk factors that induce and/or aggravate asthma,but the underlying mechanism remains unclear.Groundwater arsenic contamination have been detected in many countries around the world.Chronic arsenic exposure through drinking water has been associated with a number of diseases such as skin,lung,and bladder cancers and many non-cancer diseases.Due to the widespread arsenic contamination and its adverse health effects,chronic arsenic poisoning has become a global public health problem.To date,a large part of health effects of chronic arsenic exposure are from epidemiological investigation,and there is a lack of in vivo research data.In addition,high levels of SO₂ and arsenic co-exist in residential areas,and people are inevitably exposed to SO₂ and/or arsenic in everyday life,whereas far few data are available on the combined toxicity and health effects of SO₂ and arsenic.In view of the above questions,we proposed this topic.?1?In this study,we investigate the role of SO₂ in asthma using a classical asthmatic model with allergic airway inflammation by treating C57BL/6 mice with ovalbumin?OVA?and/or 10 mg/m³ SO₂.Our results showed that SO₂ exposure alone induced slight pathological changes but did not significantly increase inflammatory cell counts,pro-inflammatory cytokine expression,and mucus production in the airway of mice,whereas SO₂ exposure in OVA-induced asthmatic mice caused marked pulmonary pathological changes and significantly increased the counts of eosinophil-rich leukocytes compared with OVA alone asthmatic mice.The expression of MUC5 AC,TNF-?,Th2 cytokines?IL-4,IL-5,and IL-13?and STAT6 was further up-regulated in OVA plus SO₂ treated mice compared with OVA alone treated mice.In addition,exposure to SO₂ alone markedly elevated STAT6 m RNA levels and hydrogen peroxide?H₂O₂?content in the lung.These findings suggest that SO₂ amplifies Th2 inflammatory responses in OVA-induced asthmatic mice by activating STAT6,which can further induce Th2 cytokine expression and aggravate asthmatic symptoms.On the other hand,SO₂ enhanced the transcriptional inhibitory effect of OVA on bitter taste transduction pathway,which might be another important reason for SO₂ to enhance asthma susceptibility.?2?Effects of SO₂ on male reproduction of asthmatic mice were also investigated in this study.SO₂ exposure did not change testicular weight,testicular coefficient,sperm counts,or testicular structure in mice.However,the decreased sperm counts and disorganized arrangement of spermatogenic cells were observed in the mice exposed to OVA alone.SO₂ and OVA co-exposure significantly reduced the testicular weight and testicular coefficient,decreased the sperm counts,aggravated testicular tissue lesion,and changed the m RNA expression of spermatogenesis-related genes in mice.These results showed that SO₂ could aggravate the reproductive toxicity of asthmatic mice by interfering with spermatogenesis.The findings suggest that short-term low concentration of SO₂ exposure may also increase the risk of male reproductive toxicity in asthmatic patients.?3?Effects of chronic arsenic exposure on the structure and mucosal immunity were investigated in the lung and jejunum of mice.Our results showed that arsenic exposure increased malondialdehyde?MDA?content,and decreased the total superoxide dismutase activity?T-SOD?and total antioxidant capacity?T-AOC?in mouse lung and jejunum.Inflammatory cells infiltration,thicken alveolar septum,and decrescent alveolar saccules were also observed in the lung.Arsenic intake via drinking water also caused the eroded jejunal mucosa,disorganized absorptive cells,and exfoliated villi in the jejunum.The oxidative damage and the above mentioned pathological changes were more serious in 50 mg/L arsenic group than those in 5 mg/L arsenic group in both lung and jejunum.Through detecting the expression of immune-related genes,we found that long-term water intake of arsenic could increase Th1 inflammatory response,decreased Th2 anti-inflammatory response,and cause Th1/Th2 immune imbalance in mouse lung.Jejunal mucosal damage caused by arsenic might be related to As-mediated oxidative stress.The structural failure of mouse jejunum mucosal might disturb the intestinal mucosal immunity in mice.?4?In this study,we investigate male reproductive toxicity with a focus on spermatogenesis by treating mice with 5 mg/m³ SO₂ and/or 5 mg/L arsenic.Our results showed that arsenic exposure caused significant decreases in water and food consumption and body weight in mice,whereas these changes were not observed in the SO₂-only group.Both SO₂ and arsenic reduced sperm counts,increased the percentage of sperm malformation,and induced abnormal testicular pathological changes.Elevated H₂O₂ and MDA contents,declined T-SOD activity,decreased spermatogenic cell counts,enhanced caspase-3 activity,and increased TUNEL-positive cells were also observed in mice exposed to SO₂ and/or arsenic.Moreover,SO₂ and arsenic co-exposure changed the m RNA levels of Bax and Bcl-2,decreased serum testosterone levels,and downregulated the expression of steroidogenic-related genes?LHR,St AR,and ABP?in mice.These findings provide a new theoretical basis for understanding how SO₂ and arsenic interfere with spermatogenesis leading to infertility.This study provided experimental data for prevention or treatment of respiratory diseases and male infertility in polluted areas through analyzing the toxicity of SO₂ inhalation and/or arsenic intake in male mice.In view of an additive toxic effect on male reproduction,the health risks of people exposed to both SO₂ and arsenic will be further increased.