**3. Lifestyle factors and male infertility**

In general, lifestyle factors affect male reproductive system in various ways. In today's society, male infertility has become a more and more important problem. People's unhealthy lifestyle may be one of the great reasons. Sperm needs a suitable internal and external environment to complete several physiological links such as occurrence, development, maturity, and transportation. Some physical and chemical factors can lead to the damage of the testis and accessory glands, the disorders of the internal environment, and spermatogenesis dysfunction to some extent. Several studies have found that occupation, behavioral habit, dietary habit, and other factors can play a role in the decreased fertility. The following discussion focuses on the association between male infertility and lifestyle factors such as smoking, alcohol consumption, and diet.

#### **3.1. Smoking**

**2.5. Phthalates**

162 Spermatozoa - Facts and Perspectives

spermatogenesis failure [18].

**(HPG) axis**

receptors [20].

Phthalates are substances used in the manufacturing of automobiles, medical supplies, plastics, beverage containers, coating of metal cans, and so on. Data have demonstrated that perinatal exposure to a variety of phthalate esters alters the development of the male reproductive tract in an antiandrogenic way, causing underdevelopment and agenesis of the epididymis at relatively low doses [16]. Environmental exposure to di-n-butyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP) may contribute to a decline in semen quality [17]. Additionally, our recent study demonstrated that prenatal exposure to DBP has transgenerational effects of impaired spermatogenesis. We also revealed that metabolic and epigenetic changes induced by the aberrant expression of betaine homocysteine S-methyltransferase (BHMT) represent a novel mechanism linking in utero DBP exposure to transgenerational

**2.6. Mechanism(s) of action of endocrine disruptions on hypothalamic-pituitary-gonadal** 

A large amount of substances has the ability to inhibit the biosynthesis of a variety of hormones. Some substances can inhibit the specific enzymes in steroidogenesis such as aminoglutethimide, cyanoketone, and ketoconazole. Some fungicides inhibit estrogen synthesis by inhibiting aromatase activity in the testis, which has an effect on testosterone to estrogen. Through a set of signals at transcriptional and translational levels, EDCs make further efforts

Hormones react with their target tissues directly by interacting with membrane-bound receptors or intracellular receptors. The vital procedure in the function of hormones is the specific binding of natural ligand to its receptors. Intracellular or nuclear receptors interact with specific DNA sequences regulating gene transcription in a ligand-dependent pattern. This procedure might be changed by many environmental factors through mimicking the natural ligand and serving as an agonist or inhibiting the binding and serving as an antagonist. The most notable examples are methoxychlor, chlordecone, DDT, some polychlorinated biphenyls, and alkylphenols, which can disturb the function of estrogen

Epigenetic modifications characterized by DNA methylation, histone modifications, and chromatin remodeling are important regulators in spermatogenesis. Studies have shown that aberrant epigenetic modifications are associated with disturbed spermatogenesis and male infertility [21–23]. Exposure of gametes to environmental factors may cause alterations in sperm. In addition, more and more studies have demonstrated that many EDCs have trans-

Clearly, there should be more studies to explore the data gaps. In addition to a few exceptions (e.g., diethylstilbestrol [DES]), the causal relationship between exposure to specific agents and endocrine disruptor-mediated adverse health effects has not been determined. The development and validation of short-term screening studies should be used to clarify the mechanism.

generational effect of spermatogenic failure through epigenetic mechanism [3, 24].

to transform the biosynthesis of protein mediated by gonadal steroids [19].

As we know, smoking is associated with variable diseases, including respiratory diseases, cardiovascular diseases and cancer of the lung, kidney, urinary bladder, pancreas, and so on [25, 26]. The relationship between smoking and infertilities has been studied for several years.

A vast amount of studies showed the negative effects of smoking on various parameters of semen analysis. In an experiment conducted in Denmark from 1987 to 2004, 2562 men participated; researchers found that heavy smokers had a 19% lower sperm concentration than nonsmokers [27]. Moreover, in another cohort study which involves 1786 men, researchers proved that smoking was associated with a significant decrease in sperm density, total sperm count, total number of motile sperm, and citrate concentration. In addition, sperm vitality, ejaculate volume, and fructose concentration were slightly but nonsignificantly affected [28]. In other aspects, smokers had a significantly decreased semen volumes, sperm motility, and viability compared with nonsmokers. All sperm motion parameters were lower in the smokers except for beat-cross frequency (Hz). Further, the percentage of normal morphology sperm was decreased significantly in smokers, and the sperm morphology was worse with increasing degree of smoking [29]. The experiments have already shown that smoking in daily life damages the semen quality.

Existing data indicate that varicocele plays an important role in male infertility. There are also experiments trying to figure out the relationship between varicocele and smoking. In a study conducted in Iran, percentage of varicocele was significantly higher in smokers compared with nonsmokers [30].

The mechanism behind the negative effect of smoking on semen quality remains vague until today. There are evidences showing that people who smoke possess a higher proportion of spermatozoa with an alteration of the histone to protamine ratio than those who do not smoke, which may lead to male infertility [31]. Also there was a research that revealed the relationship between smoking and seminal plasma zinc level. Semen parameters were also significantly decreased among smokers with abnormal zinc levels, while there was no significant difference between nonsmokers with normal zinc and nonsmokers with abnormal zinc levels [32]. In addition, DNA methylation pattern in sperm DNA can be influenced by cigarette smoking [33]. Aberrant DNA methylation had been shown to be associated with male infertility [34].

*3.3.2. High-energy diets*

these findings.

**3.4. Other factors**

*3.4.1. High temperature*

and the damage of DNA [48, 49].

*3.4.2. Radiation*

High-energy diets, especially poor nutritional food intake with lots of unhealthy fat negatively affect semen parameters and fertility. It was described that the intake of processed meat, a source of saturated fats, is associated with poor semen quality [42]. In a cohort study conducted in the America, researchers found high intake of saturated fats was negatively related to sperm concentration whereas higher intake of omega-3 fats was positively related to sperm morphology [43]. However, studies with larger sample size are required to confirm

Environmental Factors and Male Infertility http://dx.doi.org/10.5772/intechopen.71553 165

High-energy diets may alter testicular metabolism. Testis provides an environment that nurtures the germs cells, ultimately ensuring spermatogenesis and fertility. However, the overconsumption of high-energy diets enables the increase of fatty acid supply within testicular milieu and consequently compromises the key testicular metabolic mechanisms that ultimately compromise germ cells fate [44, 45]. High-energy diets intake disturbs whole-body metabolism and the normal function of the male reproductive axis. Existing data showed that metabolism and reproduction are closely connected [46]. Obesity toxicant from the highenergy foods can promote the development of obesity and the storage of lipid-soluble toxicants in the body. Thereafter, the molecular mechanisms that regulate appetite and energy intake will gradually be disrupted. The abovementioned process cannot be separated from the mediation of gut and adipose hormones. While the major function of gut and adipose tissues is to perceive the energy status of the body, recently, some gut and fat derived hormones are thought to be a regulatory factor in reproductive events. Hence, disruption of the endo-

Some people who work under an environment with a high temperature such as blacksmith and kettleman or who had to wear clothes which are too tight for them, both factors bring about heat stress to men's testis. The process of spermatogenesis is closely related to the appropriate temperature and occurs optimally at temperature slightly lower than that of the body. Adequate adjustment of the temperature is imperative to maintain a proper testicular temperature. Raised testicular temperature has a harmful effect on spermatogenesis and the resultant spermatozoa. Therefore, thermoregulatory failure leading to heat stress can compromise the sperm quality and increase the risk of infertility [47]. Both the epididymal sperm and testicular germ cells are sensitive to damage by heat stress, which leads to the apoptosis

Cell phone usage is an indispensable part in people's daily life. As a result of which, several researchers have conducted a lot of experiments. There is a study investigating an association

crine activity of these tissues may affect the reproductive function [45].

#### **3.2. Alcohol consumption**

Excessive alcohol intake is always thought of as a cause of liver diseases, kidney diseases, and so on. In addition, alcohol consumption is considered to have an adverse impact on reproductive function. We discuss about its negative influence on the sperm parameters and the endocrine.

There was an interesting case report showing that an azoospermic patient regained normal sperm parameters 3 months after the discontinuation of alcohol consumption, which strongly supported the negative impact of alcohol consumption on male infertility [35]. Firstly, available literatures stated that alcohol consumption may give rise to spermatozoon morphological changes and the changes including breakage of the sperm head, distention of the midsection, and curling of its tail [36]. Moreover, in an experiment conducted by researchers in Argentina, which involved 537 men, it was found that alcohol consumption evoked a tendency toward diminished sperm concentration, motility, viability, and normal morphology [37].

As for its effect on the endocrine, there are masses of such studies reminding people of the impact of alcohol consumption that might cause structural testicular changes, decreased level of testosterone, which might be involved in the phenotype of hypogonadism and feminization. Alcohol and its metabolite acetaldehyde can cause a reduction in luteinizing hormone (LH) binding to Leydig cells, which may inhibit the enzymes involved in the formation of sex hormones [38]. With regard to the mechanism of its negative effects, alcohol seems to exert a dual effect on the HPG axis by directly inhibiting testicular steroidogenesis and by blocking the release of LH-releasing hormone/LH from the hypothalamic-pituitary axis [39].

#### **3.3. Diet**

### *3.3.1. Dietary bias*

Scientists found that our daily consumption of cereals, fruits, and each meal a day had a strong bearing on semen quality. Taking proper amounts of minerals, antioxidant vitamins, and essential amino acids can maintain and improve it effectively [40]. There was also a case report conducted in Spain which showed that frequent intake of lipophilic foods like meat products or milk may negatively affect the semen quality in humans, whereas some fruits or vegetables may maintain or improve semen quality [41].

#### *3.3.2. High-energy diets*

of spermatozoa with an alteration of the histone to protamine ratio than those who do not smoke, which may lead to male infertility [31]. Also there was a research that revealed the relationship between smoking and seminal plasma zinc level. Semen parameters were also significantly decreased among smokers with abnormal zinc levels, while there was no significant difference between nonsmokers with normal zinc and nonsmokers with abnormal zinc levels [32]. In addition, DNA methylation pattern in sperm DNA can be influenced by cigarette smoking [33]. Aberrant DNA methylation had been shown to be associated with

Excessive alcohol intake is always thought of as a cause of liver diseases, kidney diseases, and so on. In addition, alcohol consumption is considered to have an adverse impact on reproductive function. We discuss about its negative influence on the sperm parameters and the

There was an interesting case report showing that an azoospermic patient regained normal sperm parameters 3 months after the discontinuation of alcohol consumption, which strongly supported the negative impact of alcohol consumption on male infertility [35]. Firstly, available literatures stated that alcohol consumption may give rise to spermatozoon morphological changes and the changes including breakage of the sperm head, distention of the midsection, and curling of its tail [36]. Moreover, in an experiment conducted by researchers in Argentina, which involved 537 men, it was found that alcohol consumption evoked a tendency toward

As for its effect on the endocrine, there are masses of such studies reminding people of the impact of alcohol consumption that might cause structural testicular changes, decreased level of testosterone, which might be involved in the phenotype of hypogonadism and feminization. Alcohol and its metabolite acetaldehyde can cause a reduction in luteinizing hormone (LH) binding to Leydig cells, which may inhibit the enzymes involved in the formation of sex hormones [38]. With regard to the mechanism of its negative effects, alcohol seems to exert a dual effect on the HPG axis by directly inhibiting testicular steroidogenesis and by blocking

Scientists found that our daily consumption of cereals, fruits, and each meal a day had a strong bearing on semen quality. Taking proper amounts of minerals, antioxidant vitamins, and essential amino acids can maintain and improve it effectively [40]. There was also a case report conducted in Spain which showed that frequent intake of lipophilic foods like meat products or milk may negatively affect the semen quality in humans, whereas some fruits or

diminished sperm concentration, motility, viability, and normal morphology [37].

the release of LH-releasing hormone/LH from the hypothalamic-pituitary axis [39].

vegetables may maintain or improve semen quality [41].

male infertility [34].

164 Spermatozoa - Facts and Perspectives

endocrine.

**3.3. Diet**

*3.3.1. Dietary bias*

**3.2. Alcohol consumption**

High-energy diets, especially poor nutritional food intake with lots of unhealthy fat negatively affect semen parameters and fertility. It was described that the intake of processed meat, a source of saturated fats, is associated with poor semen quality [42]. In a cohort study conducted in the America, researchers found high intake of saturated fats was negatively related to sperm concentration whereas higher intake of omega-3 fats was positively related to sperm morphology [43]. However, studies with larger sample size are required to confirm these findings.

High-energy diets may alter testicular metabolism. Testis provides an environment that nurtures the germs cells, ultimately ensuring spermatogenesis and fertility. However, the overconsumption of high-energy diets enables the increase of fatty acid supply within testicular milieu and consequently compromises the key testicular metabolic mechanisms that ultimately compromise germ cells fate [44, 45]. High-energy diets intake disturbs whole-body metabolism and the normal function of the male reproductive axis. Existing data showed that metabolism and reproduction are closely connected [46]. Obesity toxicant from the highenergy foods can promote the development of obesity and the storage of lipid-soluble toxicants in the body. Thereafter, the molecular mechanisms that regulate appetite and energy intake will gradually be disrupted. The abovementioned process cannot be separated from the mediation of gut and adipose hormones. While the major function of gut and adipose tissues is to perceive the energy status of the body, recently, some gut and fat derived hormones are thought to be a regulatory factor in reproductive events. Hence, disruption of the endocrine activity of these tissues may affect the reproductive function [45].

#### **3.4. Other factors**

#### *3.4.1. High temperature*

Some people who work under an environment with a high temperature such as blacksmith and kettleman or who had to wear clothes which are too tight for them, both factors bring about heat stress to men's testis. The process of spermatogenesis is closely related to the appropriate temperature and occurs optimally at temperature slightly lower than that of the body. Adequate adjustment of the temperature is imperative to maintain a proper testicular temperature. Raised testicular temperature has a harmful effect on spermatogenesis and the resultant spermatozoa. Therefore, thermoregulatory failure leading to heat stress can compromise the sperm quality and increase the risk of infertility [47]. Both the epididymal sperm and testicular germ cells are sensitive to damage by heat stress, which leads to the apoptosis and the damage of DNA [48, 49].

#### *3.4.2. Radiation*

Cell phone usage is an indispensable part in people's daily life. As a result of which, several researchers have conducted a lot of experiments. There is a study investigating an association between characteristics of cell phone usage and semen quality [50]. It showed that talking for ≥1 h/day and during device charging was associated with higher rate of abnormal semen concentration. Among men who reported holding their phones ≤50 cm from the groin, a nonsignificantly higher rate of abnormal sperm concentration was found. Multivariate analysis revealed that talking while charging the device and smoking were risk factors for abnormal sperm concentration. It suggests that certain aspects of cell phone usage may bear adverse effects on sperm concentration.

utero, in the neonatal or adolescent periods, or in adulthood, and can have transgenerational effects. Despite promising discoveries, a causal relationship between male infertility and exposure to specific EDC or mixtures of EDCs is yet to be established, due to the degree of EDCs exposure, the sample size of the subjects examined, the complexity of the clinical protocols used, and the determination of the variables measured. Future studies are needed to focus on a uniform system of examining human populations with regard to the exposure to specific EDCs and its direct effect on male infertility. Considering all the lifestyle factors which result in the male infertility, to improve the severe situation of the male infertility, we should try to discontinue smoking and alcohol drinking, avoid high temperature and radiation, and maintain a balanced diet. From now on, if a good and healthy lifestyle is maintained, we will have

Environmental Factors and Male Infertility http://dx.doi.org/10.5772/intechopen.71553 167

This work was supported by National Natural Science Foundation of China (no. 81401213, 81673217), Jiangsu Overseas Visiting Scholar Program for University Prominent Young & Middle-aged Teachers and Presidents, National Key Research and Development Program (2016YFC1000207), and the Priority Academic Program for the Development of Jiangsu

Higher Education Institutions (Public Health and Preventive Medicine).

, Rong Fan<sup>2</sup>

1 State Key Laboratory of Reproductive Medicine, Department of Obstetrics, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University,

3 School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China

2 State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public

[1] Pasqualotto FF, et al. Effects of medical therapy, alcohol, smoking, and endocrine disruptors on male infertility. Revista do Hospital das Clinicas; Faculdade de Medicina da

[2] Sikka SC, Wang R. Endocrine disruptors and estrogenic effects on male reproductive

and Mu Liu3

\*, Jing Zhang2

\*Address all correspondence to: wwu@njmu.edu.cn

Health, Nanjing Medical University, Nanjing, China

Universidade de Sao Paulo. 2004;**59**(6):375-382

axis. Asian Journal of Andrology. 2008;**10**(1):134-145

offspring, bringing endless happiness.

, Wei Wu2

**Acknowledgements**

**Author details**

Qiuqin Tang<sup>1</sup>

Nanjing, China

**References**

Concerning the usage of wireless internet, researchers have demonstrated that continuous Wi-Fi exposure with 2.45 GHz affected the testes of growing rats. Avendano et al. divided the motile spermatozoa, from 29 healthy donors, into two aliquots and one of them was exposed to a Wi-Fi computer but not the other. 4 h later, research findings showed that the sperm motility and the sperm DNA fragmentation in Wi-Fi group were significantly decreased and increased, respectively [51]. However, current studies are not able to reveal the relationship well enough, and, therefore, larger scales of studies concerned about this aspect are needed.
