Air Pollution Exposure And Male Sperm Quality

BackgroundGlobally,the fertility rate of couples of childbearing age has shown a continuous downward trend in recent years.Studies have reported that about 15%of couples in the world suffer from infertility due to various reasons.Previous evidence indicates that about 20%of infertility is due to the independent effect of male factors,while about30-40%of infertility is due to the combined effect of male and female factors.In recent years,the World Health Organization has also adjusted the reference values of male sperm quality parameters in relation to the decline in sperm quality.In China,the proportion of qualified sperm donors dropped from 56%to 18%during 2001-2015,and sperm quality related parameters including sperm concentration,progressively motile sperm count,and percentage of normal-morphological sperm decreased by about 10%and 30-60%.Previous studies have shown that air pollution may be associated with decreased male sperm quality.Therefore,this study aims to explore the association between ambient air pollution and sperm quality based on a large cohort.Objectives（1）To expolore the linear and non-linear relationships between ambient air particulate matter(PM_2.5 and PM₁₀)exposure and male sperm quality;（2）To explore the linear and non-linear relationships between exposure to environmental gaseous pollutants（SO₂,NO₂,CO and O₃）and male sperm quality;（3）To explore the relationships between PM_2.5 components（metals and water-soluble ions）exposures and male sperm quality.MethodsStudy population:This study is based on a prospective cohort study of assisted reproduction in Anhui Province,China.Couples who needed assisted reproduction in Anhui Province,China and visited the Reproductive Medicine Center of the First Affiliated Hospital of Anhui Medical University were included in the cohort.This study included men between the ages of 18 and 60 from September 1,2015 to September 22,2020;male participants were also required to have at least one sperm quality test during the study period,and reported clear residential address.Subjects suffering from diseases that may lead to diseases related to the decline of sperm quality were excluded.The first part and the second part of this study used the people who met the inclusion and exclusion criteria in Anhui Province;while the third part only included the objects who met the requirements lived in the urban area of Hefei.Data collection:Demographic information,including age,height,weight,body mass index,smoking,alcohol consumption,education level,occupation type,period of abstinence,and residential address,was collected through interviews with each subject.People smoking more than 1 cigarette per day in the past 3 months was defined as current smoker,and drinking alcohol at least once every two weeks on average was considered alcohol consumption.The education level is divided into junior high school and below,high school or technical school,junior college and above.Occupations are divided into unemployed,agricultural producers（including forestry,animal husbandry or aquaculture producers）,professional/technical personnel,civil servants,soldiers or police,production workers（engaged in production or transportation equipment）and businessman or service personnel.Environmental exposure assessment:Part I and Part II:Collecting the ambient PM_2.5,PM₁₀,SO₂,NO₂,CO,O₃ daily concentrations of 76 air pollution monitoring stations and the daily ambient temperature data from 81 meteorological monitoring stations in Anhui Province.The locations of participants’residences and monitoring stations were geocoded as longitude and latitude coordinates.Using inverse distance weighted spatial interpolation to estimate the ambient temperature（°C）and exposure levels of air pollutants,including PM_2.5（μg/m³）,PM₁₀（μg/m³）,SO₂（μg/m³）,NO₂（μg/m³）,CO（mg/m³）,O₃（μg/m³）.Part III:Collecting the PM_2.5 and its components（metals and soluble ions）daily concentrtions from June 2015 to September 2020 from Hefei Center for Disease Control and Prevention.The data were measured at two fixed monitoring stations during the10th to the 16th of each month.The components include sulfate(SO₄^2-),nitrate（NO₃^-）,chloride（Cl^-）and ammonium（NH₄⁺）and aluminum（Al）,arsenic（As）,beryllium（Be）,cadmium（Cd）,chromium（Cr）,mercury（Hg）,manganese（Mn）,nickel（Ni）,lead（Pb）,antimony（Sb）,selenium（Se）,and thallium（Tl）.The daily concentration of PM_2.5 and each component was calculated from the average of the monitoring results at two stations,and was designated as the exposure level of all subjects on the corresponding day.When the average daily concentration of any component is below the method detection limit concentration,this value is replaced by the method detection limit/√2.We calculated the median daily average concentration of the study subjects from 0 to 90days before sperm detection as the individual exposure level.At the same time,the average daily ambient temperature（°C）of the subjects from 0 to 90 days before the semen test was evaluated through data from a meteorological monitoring station in Hefei.Sperm Quality Outcomes:The volume of semen（ml）was measured by weighing,and the computer aided semen analysis system was used to detect sperm concentration（10⁶/ml）,total sperm count（10⁶）,total sperm motility rate（%）,progressive spem motility rate（%）,total motile sperm count（10⁶）and progressively motile sperm count（10⁶）,which were defined as study outcome variables.Data analysis:Linear associations between air pollutants and sperm quality were assessed using linear mixed-effects models with subject-specific random intercepts to account for dependence between repeated measurements on the same subject.Because of the skewed distributions of sperm concentration,total sperm count,total motile sperm count,and progressively motile sperm count,these indicators were log-transformed before included in the regression model.Regression coefficients and their 95%confidence intervals are interpreted as the mean change of the response variable for each interquartile range unit increase in air pollutant.The potential covariates were adjusted step by step,and the specific model was as follows:Part I:Model 1:Age+Body Mass Index+Smoking+Alcohol drinking+Education level+Occupation type+Abstinence period+PM_2.5/PM₁₀Model 2:Model 1+Month+TemperatureModel 3（multi-pollutant model）:Model 2+First principal component of gaseous pollutants（SO₂,NO₂,CO and O₃）Part II:Model 1:Age+Body Mass Index+Smoking+Alcohol drinking+Education level+Occupation type+Abstinence period+SO₂/NO₂/CO/O₃Model 2:Model 1+Month+TemperatureModel 3（multi-pollutant model）:Model 2+PM_2.5 exposure level Part III:Model 1:Age+Body Mass Index+Smoking+Alcohol drinking+Education level+Occupation type+Abstinence period+Month+Temperature+Individual metal/water-soluble ion;Model 2:Age+Body Mass Index+Smoking+Alcohol drinking+Education level+Occupation type+Abstinence period+Month+Temperature+PM_2.5+Individual metal/water-soluble ion;Model 3:Age+Body Mass Index+Smoking+Alcohol drinking+Education level+Occupation type+Abstinence period+Month+Temperature+Individual metal residuals/water-soluble ion residual.In the first part and the second part of the study,in order to explore the potential non-linear trend between air pollutants and sperm quality,we further divided the research population into deciles（D1-D10）according to the air pollutant exposure levels;And then we assingned the median of the exposure level of air pollutentas in each group（D1-D10）to replace the original value for regression analysis to calculate the significance of the linear trend.At the same time,the decile analysis was used by including the transformed categorical variable（D1-D10）into the research model with D1 group as the reference and calculating the regression coefficients of D2-D10 groups,the potential non-linear trend is determined through the change-trend of the regression coefficients of D2-D10 groups.In the second part of the study,in order to further verify the non-linear trend between gaseous pollutants and sperm quality,we used natural cubic spline function to evalute the potential non-linear relationship between gaseous pollutants and sperm quality.Two equidistant nodes were selected within the range of the exposure levels of each gaseous pollutant in each exposure window.When a significant non-linear association was found,the non-linear dose-response relationship was further quantitatively assessed using piecewise regression.In the third part of the study,we simultaneously performed weighted quantile sum（WQS）regression to assess the combined effect of multiple components.ResultsPart I:The average exposure level of PM_2.5 and PM₁₀ in the 0-90,0-9 and 70-90 day exposure windows were negatively associated and the sperm concentration,total sperm count,total sperm motility rate,progeressive motility rate,total motile sperm count and progeressively motile sperm count（all P<0.05）.Decile regression did not reveal a potential non-linear association between PM_2.5 and PM₁₀ exposures with sperm quality.The effect sizes of PM_2.5 exposure on semen quality parameters in the 0-90 day exposure window were larger than that in the 0-9 day and 70-90 day exposure windows,and the effect sizes of PM_2.5 exposure on semen quality parameters were stronger than that of PM₁₀.Part II:Ambient SO₂ exposure levels were negatively associated with all semen quality parameters（all P<0.05）,except for progressive motility rate in the 0-90-day and70-90-day exposure windows,which were not significantly correlated.There was a"J"or"U"shaped dose-response relationship between ambient SO₂ exposure level and total sperm count,progressive motility rate,total sperm motility rate,progressively motile sperm count,and total motile sperm count（non-linear P<0.05）,but no non-linear relationship with sperm concentration was found.Simultaneous piecewise regression analysis showed that there was a negative correlation between SO₂ exposure level and semen quality only when the SO₂ exposure level was below the cutoff points determined by the cubic spline analysis,which were all less than 40μg/m³,the recommended exposure level for SO₂ in the updated WHO air quality guidelines.Part III:Among PM_2.5 bound metals,antimony,arsenic,cadmium,lead,and thallium were significantly negatively associated with semen quality parameters,and among water-soluble ions,SO₄^2-and Cl^-exposure levels were also negatively associated with semen quality parameters.PM_2.5-bound metals and water-soluble ions as a mixture combinedly or respectively had significantly adverse effects on semen quality.ConclusionsOur results showed that ambient PM_2.5 and PM₁₀ exposure levels were associated with decreased semen quality at exposure windows of 0-9 days,70-90 days,and 0-90 days before sampling.PM_2.5 had a stronger effect on semen quality parameters than PM₁₀,and both PM_2.5 and PM₁₀ had stronger long-term effects than short-term effects throughout spermatogenesis.Overall,we also found inverse associations between SO₂ exposure levels and semen quality.The ambient SO₂ exposure level may have reached the maximum dangerous dose below the SO₂ exposure level recommended by the WHO air quality guidelines,which suggests that when considering male reproductive health,the current air quality guidelines may need further discussion.We also found that certain components of PM_2.5 were negatively correlated with semen quality,especially metals.Antimony,lead and thallium are the main causes of PM_2.5toxicity to semen quality.