How Environmental and Air Pollution Disrupt Spermatogenesis and Male Reproductive and Sexual Health: AnEpidemiological and Mechanistic Approach

Background: Through a series of research projects and experiments,we have demonstrated the link between environmentaland air pollution and general health of an individual and apopulation living in industrialized and urban city (Sao Paulo)using male infertility and erectile function/dysfunction, butnot limited in their own scope of disease, but also in a broaderperspective as bio markers of global reproductive and sexualhealth in a population-based analysis. Also, we analyzed in twostudies if positive government mitigating policies redounded inimprovement of the same parameters. Sex ratio at birth, or secondarysex ratio (SSR), can be understood as the ultimate resultof the battle between maternal and paternal genomes. In thisbattle of gene interests, sex determination, genomic imprinting,X chromosome inactivation, and meiotic drive are the mainmechanisms regulating sperm and oocyte production, fertilization,nearly development, fetal survival, and reproductive fitness.Sex ratio skew in which a female-biased litter may occurin some mammalian species under both field and experimentalstressful conditions, such as food availability and air pollution,but have been mainly studied from the oocyte perspective, notfrom the male gamete perspective.Materials an Methods: A series of epidemiological, observationaland research projects gathering in each one from hundredsof individuals to hundreds of thousands to even millionsof births involving sex-ratio disturbances in polluted areas tosemen quality alterations in populations and/or workers heavilyexposed to vehicular emissions and biomass burning where weobtained data from ۲۰۵,۰۰۰ births from selected cities with over۱۰۰ million tons/cane production per year and collected informationon the extension of the sugar cane plantation area andnumber of foci of fires on a daily basis by satellite monitoring,and subdivided them in five categories according to the relationshipbetween cane plantation area and the role area of thecity: ۰-۱۵%, ۱۶-۳۰%, ۳۱-۴۵%, ۴۶-۶۰%,>۶۰%. In another study,semen quality was used as end-point in pre-vasectomy fertilepatients over almost a decade to analyze prospectively the effectsof air pollution. Using erectile function as a bio marker,we conducted an epidemiological study in the Amazon rain forestto study how an isolated population with good health habitsand non-industrialized food consumption in an environmentally-free of pollution stands for sexual quality of life. Reactiveoxygen species and sperm quality tests were performed in somestudies.Results: I will point out results, study by study. Study on decreasedsemen quality in a fertile population: Data between۲۰۰۰ and ۲۰۰۸ from ۷۴۳ patients aged between ۲۳ and ۵۰ years(mean ۳۶.۵ years old) in the city of São Paulo clearly demonstratesa decrease in semen parameters in healthy donors. Seminalanalysis was performed according to the WHO and strictcriteria. Daily data of air concentrations of O۳, CO, NO۲, SO۲,and PM۱۰ were collected and plotted to the specific individualsexposed. Seminal analysis parameters (concentration, motility,morphology) were correlated with daily data of air pollutionseparated into quartiles and corresponding to collection date. Sperm concentration (million/mL; r=۰.۰۶, P=۰.۰۷۹) and morphology(%WHO; ۰.۰۱۴, P=۰.۶۹۹) were not statistically differentwithin different ages, but progressive motility (A + B%)showed negative correlation with time in these ۸ years’ time(%; r=−۰.۱۸, P≤۰.۰۰۱). Studies on sex-ratio: We have elegantlydemonstrated a significant sex ratio decrease in the most pollutedareas of São Paulo city, Brazil. Results disclosed a significantnegative association (r۲=۰.۷۶۴۲, P=۰.۰۱۳) between SSRand PM۱۰ within a relatively narrow range of PM۱۰ levels (۳۱-۶۱ μg/m۳). In the least polluted area the sex ratio was ۵۱.۷%(۱۰۶.۸) for ۳۴,۷۹۵ births recorded, and for the most pollutedarea the proportion decreased to ۵۰.۷% (۱۰۲.۹) for ۴۸,۰۲۳ birthsrecorded. This result corresponds to a difference of ۱% in totalmale births or ۱.۱۸۰ fewer male births in the highest pollutedareas per year. Similar findings were observed in the experimentalstudy. After exposure, reproductive mature and nonexposedvirgin female mice were placed in the chambers to mate. Therefore,male Swiss mice housed ۱۰ days after birth in open topchambers exposed to air pollution, where they mature and mateto nonexposed virgin female mice, produced an offspring witha ۰.۸۶ male/female ratio. The offspring of the group of miceconcurrently raised in a similar but filtered open-top chamberwere significantly (P=۰.۰۴۲) higher (۱.۳۴). Sex ratio was studiedin ۲۷ million births in five major regions of this continentalcountry and compare results from the United Nations Index ofHuman Development. Interestingly, we found that sex ratio isdecreased in the southeast and southern regions, which are byfar the most developed, industrialized, and polluted areas. Resultsare: ۱. North (۵۱.۴۱%), ۲. Midwest (۵۱.۳۹%), ۳. Northeast(۵۱.۳۷%), Southeast (۵۱.۱۶%), and South (۵۱.۲۲%). Statisticaldifferences: Northeast versus Southeast (P=۰.۰۰۲); North versusNortheast (P=۰.۰۰۴۱). In the sugar-cane biomass burningresults demonstrated a decrease in sex ratio by ۰.۳% (P=۰.۰۱).Results demonstrated sex ratio reestablishment with decreasedPM۱۰ over ۵ years in Sao Paulo in large areas where mitigationpolicies were introduced. In the study of traffic-controllers ourresults indicate a decrease in progressive motility much abovethe already decreased motility in the control group exposed toregular air pollution and both are worse when compared withpre-vasectomy patients of control group. nonpolluted areas.Morphology by strict criteria was also significantly reduced andantisperm antibodies were higher in the traffic controllers thanin the control group. Finally, quality of sexual life is maintainedin the Amazon isolated-area population-based study, even atolder ages of ۶۵ to ۷۰ y.o. and can be compared with muchyounger individuals in the same region. The response rate was۸۱.۶۹%. The mean age was ۳۶.۰۰ ± ۱۲.۹۵ years, and most menhad mixed ethnicity (۶۳.۱۱%), were self-employed (۴۲.۰۷%),had a monthly earned income of US$۰ to US$۴۶۰ (۴۶.۷۵%),and were single (۳۶.۱۰%). The mean MSQ score was ۸۰.۳۹ ±۱۲.۱۴ (highly satisfied). None of the demographic characteristicsshowed a statistically significant influence on sexual satisfaction.The difference in quality of sexual life was statisticallysignificant compared with age (P<۰.۰۱). The domains of desire(P<۰.۰۱), partner satisfaction (P<۰.۰۴), and erection quality(P<۰.۰۱, P<۰.۰۳, P<۰.۰۲) were statistically significant.Conclusion: There is compelling evidence of the harmful effectsof exposures to environmental pollution on reproductivehealth from our studies. One conclusion that can be drawn isthat the sex ratio skew presented here represents a primary sexratio (PSR) skew instead of an SSR skew often caused by preferentialmales’ losses, once the litter sizes were similar and noincrease in abortions was seen. If the PSR is reduced, we musthypothesize that the histological differences presented by theexposed animals can represent only the tip of the iceberg of otherdeeper testicular modifications. Molecular and chromosomalevents such as altered imprinting patterns, X-Y pairing errors,and oxidative stress could have led to skew or skill “superiority”of X-bearing sperm. As a conclusion for this part of thechapter, sex ratio and its variants can be used as bioindicators ofreproductive health and help scientists with powerful tools andarguments to delineate government policies. Preserved qualityof sexual life in the Amazon was a demonstration that men’shealth is linked to the environment that surrounds each individual,we were not designed to so many stressful conditionsimposed by post-modern society in the last hundreds of years.

کلیدواژه ها:

Environmental Air Pollution ، Reproductive Health ، Male Infertility ، Erectile Dysfunction ، Spermatozoa