**The Role of Human Semen as an Early and Reliable Tool of Environmental Impact Assessment on Human Health** The Role of Human Semen as an Early and Reliable Tool of Environmental Impact Assessment on Human Health

DOI: 10.5772/intechopen.73231

Luigi Montano, Paolo Bergamo, Maria Grazia Andreassi and Stefano Lorenzetti Luigi Montano, Paolo Bergamo, Maria Grazia Andreassi and Stefano Lorenzetti

Additional information is available at the end of the chapter Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.73231

#### Abstract

Several studies have shown a dramatic reduction of semen quality in many industrialized countries and infertility is becoming a public health top priority, whose incidence is associated to late-onset adult diseases, especially cancer, shorter life expectancy and trans-generational effects. The male reproductive system is particularly sensitive to a broad variety of reproductive and developmental toxicants, including many environmental pollutants and recent studies suggest that human semen is an early and sensitive environmental and health marker. A set of semen biomarkers is described for reproductive health effects in relation to environmental exposure, where human semen seems to be an early and sensitive source of biomarkers than blood to monitor high environmental pressure on human health. Environmental health should consider reproductive health and development, from intrauterine life to childhood and puberty: these are both vulnerable targets and high-value protection goals, inasmuch as they represent the future of our societies. Hence, biomarkers of reproductive health should be exploited as early signals of environmental pressure and increased risk of adverse chronic health effects so that the use of "human seminal model" might be the main objective to be considered in the agenda of public prevention policies for early detection and innovative programs of health surveillance in environmental risk areas.

Keywords: semen quality, pollution, DNA sperm damage, environmental marker, health marker, endocrine disruptors, sperm telomere, redox status, epigenetic, aneuploidies, reproductive health, environmental health

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and eproduction in any medium, provided the original work is properly cited.

#### 1. Introduction

Since the early 1950s, in several demographic surveys a steady decline of birth rates in all European countries has been observed [1]. In particular semen quality was highly decreased in many industrialized countries [2–4] and in many European, Japanese and American young people poor semen quality was associated with subfertility or even infertility [5, 6]. The risk is that semen quality of a significant proportion of young men in developed countries will impair the fecundity potential causing on a short-term basis just a longer waiting time to pregnancy without to considerably family sizes of modern couples [7, 8], but on a middle-, long-term basis, strongly contributing (along with socio-economic factors) to the already observed European decrease in the birth rate. While there was a considerable variability in trends in sperm counts over the past 20 years, several recent studies have reported that 20–30% of young men today have sperm concentration below 40 106 /ml, which is associated with reduced fecundity [9–11]. Among life-style changes that contribute to a reduced birth rate, affecting semen parameters and/ or semen quality, there are: increased age at conception of both parents (although as a consequence of socio-economic factors), the increase in obesity, physical inactivity and the exposure to environmental and dietary environmental and chemical contaminants, including drugs. Exposure to man-made chemicals, in particular in the workplace, is recognized as major risk factors for male infertility in both epidemiological and experimental studies [12–16]. Individuals exposed for professional reasons to environmental contaminants show a reduction of concentration, motility, morphology and/or sperm DNA damage. In addition, toxicological studies in animal models are reporting DNA damages or epigenetic alterations within the germline: exposure to environmental xenobiotics during the fetal development and in early post-natal life, caused congenital malformations or reproductive tissue alterations or reduced fertility or signs of reproductive syndromes, such as the testicular dysgenesis syndrome, in particular when multiple in utero exposure to chemicals are tested. Furthermore, gene expression of genes mediating hormone (e.g. sex steroid hormones) actions is affected by epigenetic alterations even after some generation from the exposure to chemicals showing that the adverse effects can be eventually recorded only in next generations. A milestone in understanding the pathogenesis of testicular tumor has been the discovery of the fact that its onset in adults results from cancer cells in situ, which are transformed germ cells of the gonocyte type, which have failed to differentiate into spermatogonia during the fetal period [17, 18]. More strikingly, especially in industrialized countries, the reduction of semen quality and/or semen count present differences in areas within the same country or even in the same region supporting the idea that environmental factors, present in some areas but not in others, may be responsible for the decline in semen quality and sperm count [19–27]. Furthermore, different studies have reported that in high environmental pressure areas there is both an increase of infertility, urogenital malformation and chronic disease (cancer, diabetes, etc.) [28–32]. These epidemiological data are important to understand the shared biological mechanisms mediated by contaminants. In fact, infertility is becoming a public health top priority because, in addition to psychological distress and high economic costs, there are more and more evidences of diseases associated with poor semen quality [33] including crossgenerational effects [34, 35], shorter life expectancy [36], testicular cancer [37–41] and overall other types of cancer [42, 43]. However, the first systematic study regarding environmental

pollution and human reproduction has been conducted in the Czech Republic within the research program "Teplice" [44]. In particular, with regard to the impact on the semen quality, it has been proved a positive correlation between the increased concentration of polycyclic aromatic hydrocarbons (PAHs) in atmospheric pollution as well as of airborne particulate matter (PM), with an aerodynamic diameter smaller than 10 μm (PM10), mainly in winter, and an increase in fragmentation of sperm chromatin, DNA-PAHs adducts, abnormal sperm shapes and in the rate of sperm aneuploidies [45]. Other human biomonitoring studies have documented widespread human exposure to chemicals [46, 47] and actually the European Commission has financed the Human Biomonitoring Initiative (HBM) (https://ec.europa.eu/ research/conferences/2016/hbm4eu/index.cfm) to promote the generation of current HBM data throughout Europe as well as the development of new biomarkers of exposure for chemicals. However, knowing the environmental pollutant concentrations in the environment and their seasonal variability, is essential to consider each source of exposure related to individual lifestyle (including living places, dietary habits, use of cosmetics, plastic bottles, personal computers, wireless internet and much more), and the plausibility of the cause-to-effect relationship among the real life mixture of dietary and environmental contaminants, the tissue/biological fluid levels at which chemicals (or their metabolites) are present in the human body and human disorders and/or pathologies. From this stage onwards, how much chemical values are measurable in fluids or tissues (biomarkers of exposure) and to which extent they are associated with a biological effect (biomarkers of effect) depending on specific, individual response (markers of genetic susceptibility, polymorphisms, etc.) will define a complete risk assessment founded on a reliable Adverse Outcome Pathway (AOP) in which each sequential step is linked to the other. Furthermore, in order to adopt an effective primary prevention strategy, it will be important to identify not only the source and extent of the exposure but also the tissue or organ most sensitive to such exposure and, simultaneously, the biological tool more sensitive and reliable to predict future alterations and to detect the earliest clinical risk indices. Dietary and environmental chemicals exposure may influence human endocrine and metabolic homeostasis and, especially, the reproductive system. Among the reproductive system targets, the male reproductive system could be considered a general health check detector since it is particularly and uniquely sensitive to a broad variety of reproductive and developmental toxicants, including many environmental pollutants, throughout the lifespan. Indeed, spermatogenesis and secretory fluids of the differentiated accessory glands of the male reproductive system are continuously renovated starting from newly differentiating staminal cells, thus making them a feasible target to study both shortand long-term effects of chemical exposure. The male germline accumulates mutations faster than the female one [48, 49]. For instance, it is thought that sperm cells are more susceptible than eggs to the effects of oxidative damage [50] and recent studies have demonstrated the association between semen quality and state of health, correlating the semen quality with either chronic degenerative diseases, comorbidities and even mortality [51–53]. Thus, spermatogenesis is a cycle extremely complex and vulnerable to endogenous and exogenous stress and that human semen can become an important "environmental and health marker". In this way, the qualitative assessment of human semen might be envisaged as a potential focus for future development of public prevention policies. Therefore, the use of reproductive biomarkers as environmental health risks was proposed as a promising/ innovative strategy for the early detection and pre-

The Role of Human Semen as an Early and Reliable Tool of Environmental Impact Assessment on Human Health

http://dx.doi.org/10.5772/intechopen.73231

175

vention of environmental health [54].

1. Introduction

174 Spermatozoa - Facts and Perspectives

have sperm concentration below 40 106

Since the early 1950s, in several demographic surveys a steady decline of birth rates in all European countries has been observed [1]. In particular semen quality was highly decreased in many industrialized countries [2–4] and in many European, Japanese and American young people poor semen quality was associated with subfertility or even infertility [5, 6]. The risk is that semen quality of a significant proportion of young men in developed countries will impair the fecundity potential causing on a short-term basis just a longer waiting time to pregnancy without to considerably family sizes of modern couples [7, 8], but on a middle-, long-term basis, strongly contributing (along with socio-economic factors) to the already observed European decrease in the birth rate. While there was a considerable variability in trends in sperm counts over the past 20 years, several recent studies have reported that 20–30% of young men today

Among life-style changes that contribute to a reduced birth rate, affecting semen parameters and/ or semen quality, there are: increased age at conception of both parents (although as a consequence of socio-economic factors), the increase in obesity, physical inactivity and the exposure to environmental and dietary environmental and chemical contaminants, including drugs. Exposure to man-made chemicals, in particular in the workplace, is recognized as major risk factors for male infertility in both epidemiological and experimental studies [12–16]. Individuals exposed for professional reasons to environmental contaminants show a reduction of concentration, motility, morphology and/or sperm DNA damage. In addition, toxicological studies in animal models are reporting DNA damages or epigenetic alterations within the germline: exposure to environmental xenobiotics during the fetal development and in early post-natal life, caused congenital malformations or reproductive tissue alterations or reduced fertility or signs of reproductive syndromes, such as the testicular dysgenesis syndrome, in particular when multiple in utero exposure to chemicals are tested. Furthermore, gene expression of genes mediating hormone (e.g. sex steroid hormones) actions is affected by epigenetic alterations even after some generation from the exposure to chemicals showing that the adverse effects can be eventually recorded only in next generations. A milestone in understanding the pathogenesis of testicular tumor has been the discovery of the fact that its onset in adults results from cancer cells in situ, which are transformed germ cells of the gonocyte type, which have failed to differentiate into spermatogonia during the fetal period [17, 18]. More strikingly, especially in industrialized countries, the reduction of semen quality and/or semen count present differences in areas within the same country or even in the same region supporting the idea that environmental factors, present in some areas but not in others, may be responsible for the decline in semen quality and sperm count [19–27]. Furthermore, different studies have reported that in high environmental pressure areas there is both an increase of infertility, urogenital malformation and chronic disease (cancer, diabetes, etc.) [28–32]. These epidemiological data are important to understand the shared biological mechanisms mediated by contaminants. In fact, infertility is becoming a public health top priority because, in addition to psychological distress and high economic costs, there are more and more evidences of diseases associated with poor semen quality [33] including crossgenerational effects [34, 35], shorter life expectancy [36], testicular cancer [37–41] and overall other types of cancer [42, 43]. However, the first systematic study regarding environmental

/ml, which is associated with reduced fecundity [9–11].

pollution and human reproduction has been conducted in the Czech Republic within the research program "Teplice" [44]. In particular, with regard to the impact on the semen quality, it has been proved a positive correlation between the increased concentration of polycyclic aromatic hydrocarbons (PAHs) in atmospheric pollution as well as of airborne particulate matter (PM), with an aerodynamic diameter smaller than 10 μm (PM10), mainly in winter, and an increase in fragmentation of sperm chromatin, DNA-PAHs adducts, abnormal sperm shapes and in the rate of sperm aneuploidies [45]. Other human biomonitoring studies have documented widespread human exposure to chemicals [46, 47] and actually the European Commission has financed the Human Biomonitoring Initiative (HBM) (https://ec.europa.eu/ research/conferences/2016/hbm4eu/index.cfm) to promote the generation of current HBM data throughout Europe as well as the development of new biomarkers of exposure for chemicals. However, knowing the environmental pollutant concentrations in the environment and their seasonal variability, is essential to consider each source of exposure related to individual lifestyle (including living places, dietary habits, use of cosmetics, plastic bottles, personal computers, wireless internet and much more), and the plausibility of the cause-to-effect relationship among the real life mixture of dietary and environmental contaminants, the tissue/biological fluid levels at which chemicals (or their metabolites) are present in the human body and human disorders and/or pathologies. From this stage onwards, how much chemical values are measurable in fluids or tissues (biomarkers of exposure) and to which extent they are associated with a biological effect (biomarkers of effect) depending on specific, individual response (markers of genetic susceptibility, polymorphisms, etc.) will define a complete risk assessment founded on a reliable Adverse Outcome Pathway (AOP) in which each sequential step is linked to the other. Furthermore, in order to adopt an effective primary prevention strategy, it will be important to identify not only the source and extent of the exposure but also the tissue or organ most sensitive to such exposure and, simultaneously, the biological tool more sensitive and reliable to predict future alterations and to detect the earliest clinical risk indices. Dietary and environmental chemicals exposure may influence human endocrine and metabolic homeostasis and, especially, the reproductive system. Among the reproductive system targets, the male reproductive system could be considered a general health check detector since it is particularly and uniquely sensitive to a broad variety of reproductive and developmental toxicants, including many environmental pollutants, throughout the lifespan. Indeed, spermatogenesis and secretory fluids of the differentiated accessory glands of the male reproductive system are continuously renovated starting from newly differentiating staminal cells, thus making them a feasible target to study both shortand long-term effects of chemical exposure. The male germline accumulates mutations faster than the female one [48, 49]. For instance, it is thought that sperm cells are more susceptible than eggs to the effects of oxidative damage [50] and recent studies have demonstrated the association between semen quality and state of health, correlating the semen quality with either chronic degenerative diseases, comorbidities and even mortality [51–53]. Thus, spermatogenesis is a cycle extremely complex and vulnerable to endogenous and exogenous stress and that human semen can become an important "environmental and health marker". In this way, the qualitative assessment of human semen might be envisaged as a potential focus for future development of public prevention policies. Therefore, the use of reproductive biomarkers as environmental health risks was proposed as a promising/ innovative strategy for the early detection and prevention of environmental health [54].
