**1. Introduction**

The higher predominance of smoking is seen among youthful men during their fertility period. It is estimated that almost half of smokers, in the world, are aged between 20 and 39 years old [1, 2].

Infertility is a complicated condition in which contribute environmental lifestyle, genetic, and epigenetic factors [3, 4].

Different studies showed that semen parameters may be affected by various lifestyles, advancement in technologies, environmental pollution [5], alcohol intake [6], smoking [7–9].

Smoking and chewing tobacco are the harmful addictions [10] that include a variety of toxic, mutagenic, and carcinogens substances, together with nicotine reported for adversely affecting semen quality and consequently male infertility [11, 12].

#### **1.1 Hormone regulation disruption**

The most toxic compound in tobacco products is nicotine. It is a psychoactive drug and an oxidizing substance, which is addictive. The nicotine in any tobacco product readily absorbs into the blood when a person uses it. Nicotine may change the hypothalamic– pituitary axis (HPG) by enhancing the release of cortisol, growth hormone, oxytocin, and vasopressin, which in turn inhibit the prolactin and the luteinizing hormone (LH) [13].

Heavy smokers are the most facing fertility problems than nonsmokers [14]. Studies showed that in smokers, the mean levels of prolactin (PRL), follicle-stimulating hormone (FSH), mean levels of LH were lower, and the mean estradiol (E2) levels were higher in comparison to nonsmokers [15]. The same is observed in another study where testosterone, E2, LH, and FSH levels are lower in smokers [16].

In contradiction, no differences in serum total testosterone, LH, and FSH levels were demonstrated among fertile male patients divided into heavy, moderate, and mild smokers [17].

Moreover, substances in tobacco smoke affect pituitary, thyroid, adrenal, and testicular functions and consequently alter semen quality of both infertile and fertile men [18], leading to a change in testosterone, E2, PRL, LH, and FSH levels, which may cause Leydig and Sertoli cell failure in smokers [19–22].

#### **1.2 Erectile dysfunction**

Smoking have been demonstrated to be a hazard factor for erectile dysfunction, a condition in which man is incapable to induce or keep an erection firm sufficient for satisfactory sexual intercourse [23].

In Korea, after a survey among 600 men aged between 40 and 80, they found that ejaculatory and erectile functions malfunction was associated with previous and current smoking habit [24].

In Australia, a second study found that ED was associated with cigarette smoking, and even this association became stronger in heavier smokers [25].

Shiri and colleagues demonstrated that the risk for ED from smoking was generally little, and the smokers had decreased chances of recuperating from ED compared with nonsmokers [26].

A group of researchers showed an association between smoking more than 20 cigarettes daily and nearly 50% high risk of erectile dysfunction [27].

He et al. concluded a relationship between nearly 12 million cases of ED in Chinese men and smoking and reported a significant dose–response association between smoking and the risk of ED [28].

Cao et al. confirmed a significant association between smoking and the high risk of ED. Besides, quitting smoking significantly improved both physiological and sexual wellbeing in male smokers, notwithstanding the level of erectile dysfunction [29].

#### **1.3 Smoking and oxidative stress**

The compounds of a cigarette enhance superoxide generation by both endothelial and smooth muscle cells from NADPH oxidase (NOXs) and uncoupled endothelial

#### *Smoking and Its Consequences on Male and Female Reproductive Health DOI: http://dx.doi.org/10.5772/intechopen.104941*

nitric oxide synthase (eNOS) and upregulate proinflammatory cytokines and the Ras homolog gene family, member A (RhoA), and its downstream effector Rhoassociated protein kinase (ROCK) (RhoA/ROCK) contractile pathway. This process leads to reduction of nitric oxide (NO) bioavailability, endothelial dysfunction, and increase of vasoconstriction [30].

Reactive oxygen species (ROS) also affect hypothalamic–pituitary-thyroid axis and reduce triiodothyronine (T3) and thyroxine (T4) secretion. Low levels of T3 reduce the levels of the protein in Leydig cells and the steroidogenic acute regulatory (StAR) mRNA, along with testosterone production [31]. ROS production interferes oxygen delivery to the testis, which is crucial for spermatogenesis [32, 33].

A possible cause of the harmful effects of nicotine and other compounds of tobacco, on the male genital tract, is the release of mediators of inflammation, such as interleukin-8 and interleukin-6, which may enroll and actuate leucocytes [34, 35].

Successively, activated leukocytes lead to excessive ROS production in semen. Studies reported high levels of oxidative stress markers such as ROS malondialdehyde (MDA) and smoking markers such as cotinine in seminal plasma of smokers [9, 36]. Even expression of antioxidant enzymes and seminal vitamin C was insufficient to provide full protection of spermatozoa [37].

Furthermore, the high levels of ROS and cotinine in seminal plasma were associated with the number of daily cigarettes. The higher consumption means a severe damage in the sperm membrane because of its polyunsaturated fatty acids composition [38].

### **1.4 Smoking and sperm parameters: Concentration, motility, and morphology**

As mentioned before, tobacco and its compounds lead to an excessive production of ROS. The key mechanism responsible for sperm damage is the lipid peroxidation of spermatozoa membrane caused by ROS. As a result, sperm concentration, viability, mobility, and normal morphology decrease [39, 40].

It alters the fertilizing capacity of the sperm [41] and reduces antioxidant activity, which has possible adverse effect on sperm density, motility, and morphology [9, 42].

Calogero et al. demonstrated that Cigarettes Smoke Extract (CSE) in healthy nonsmokers men could suppress sperm motility and alters chromatin condensation. Besides, in a concentration- and time-dependent manner, CSE induces early apoptotic sign and a late apoptotic sign: fragmented sperm DNA [43].

In comparison to mainstream smoke, sidestream smoke contains several toxicants at higher levels including ROS such as superoxide and hydrogen peroxide [34, 40], as well as cadmium [34, 44]. They have also shown to affect semen quality and cause disturbance in sperm acrosome function [39].

Therefore, passive smokers are concerned with this problem. They are 2.5 times more exposed to cancerous substances in tobacco than active smokers [45, 46].

#### **1.5 Smoking and sperm DNA fragmentation in sperm**

The most frequent DNA anomaly is DNA fragmentation, which is associated with poor spermatozoa quality, low fertilization rates, and bad embryo quality [47].

Sperm DNA fragmentation is generally induced by oxidative stress and/or apoptosis [48, 49].

Oxidative stress (OS) caused by smoking induces oxidative DNA damage of the spermatozoa [50] and mutagenic adducts [51]. Thus, it leads to alteration of sperm quality and may cause male infertility [52].

Different techniques were used to measure the spermatozoa DNA damage. The latter showed an association with various assisted reproductive technology (ART) outcomes such as fertilization rate, embryo quality, implantation rate, pregnancy, and spontaneous abortion [53]. So, an elevated DNA damage is associated with low implantation and consequently, low pregnancy rate [54].

In men with idiopathic infertility, associated with cigarette smoking, an increase in sperm DNA stainability, sperm DNA fragmentation index, and spermatozoa with round head were noticed [55].

In addition, it has been suggested that DNA damage is the main cause of implantation failure in embryos derived from healthy eggs fertilized by sperm with chromatin defects [56, 57]. These negative effects of smoking on spermatozoa and the damage to the DNA may be due to excessive ROS production [58] and decrease the antioxidant levels in seminal plasma [42].

Dai et al. also reported that tobacco smoking negatively affects sperm parameters, such as volume, concentration, motility, morphology, and viability, leading to male infertility [59].

Moreover, an excessive production of ROS leads to oxidative stress; in turn it affects not only sperm nuclear DNA but also sperm mitochondrial respiratory activity [60] and the endocrine function resulting in several pathologies of the male reproductive system and may be leading to male infertility [61, 62].
