**5. HPV and** *Chlamydia trachomatis* **co-infection in the decrease of sperm quality**

It has been written that the cause of infertility may be multifactorial and its etiology – viral and bacterial agents – is of particular interest because of its prevalence. HPV and *Chlamydia trachomatis* are commonsexually transmittedinfections that couldbe associated with infertility.

Infection with HPV has been identified as one of the possible causes associated with male infertility, although the mechanisms that may be using this virus are not yet clear. However, it was found that HPV can act both at conception and gestational development. Although there are different places where HPV may be infecting, as mentioned in the first section, the main concern linked to infertility is regarding the quality of sperm [18].

Other studies confirm this last statement which demonstrates a significant reduction in sperm motility while other parameters were not affected (semen volume, pH, normal morphology, viability, sperm concentration) [49] and cell desquamation. Sperm infected by HPV can go on to introduce the virus to the oocyte when being fertilized, which can have different conse‐ quences such as underdevelopment of the fetus. It has been observed that couples undergoing *in vitro* fertilization and abortion are at high risk of HPV from semen samples [18]. Therefore, diagnosis of HPV should be included in the diagnosis of infertility especially when considering cases of pregnancy loss [20] (Figure 2).

Decrease in Sperm Quality due to Infection of Human Papilloma Virus and *Chlamydia trachomatis* http://dx.doi.org/10.5772/63717 75

**Figure 2.** Effect of human papillomavirus and *Chlamydia trachomatis* in sperm

found to be 6% and 28%, respectively; 19 genotypes were detected – proving to be the most common were HPV-5 and 11 [41]. In a previous study of our working group we found that of 77 patients with squamous intraepithelial lesions 13% had a co-infection with HPV and *Chlamydiatrachomatis*;46%onlyHPVinfectionand13%only*Chlamydiatrachomatis*infection[42].

In another study, it was found that patients with *Chlamydia trachomatis* and HPV had a prevalence of 74 %. However, only 13% of patients were negative to HVP and positive to *Chlamydia trachomatis* [43]. In the case of sexually transmitted infections *Chlamydia trachoma‐ tis* was found in 50% and HPV in 30% [44]. Other studies show that *Chlamydia trachomatis* infection is associated with multiple HPV genotypes and changes in signaling mechanisms in

As mentioned in the above paragraphs the relationship between infection of HPV and *Chlamydia trachomatis* is confirmed, however, few studies exist regarding infertility in men with high prevalence. It has been found that men who have HPV present *Chlamydia trachomatis* 82.8% compared to a negative HPV of 17.2% [47]. In another study a prevalence of HPV in the semen of men with conjugal infertility was of 38.5 %, meanwhile the prevalence of *Chlamydia*

There are few studies showing the association of the two pathogens as co-factors with male infertility, however, there are multiple studies showing their coexistence, so it is important to

**5. HPV and** *Chlamydia trachomatis* **co-infection in the decrease of sperm**

It has been written that the cause of infertility may be multifactorial and its etiology – viral and bacterial agents – is of particular interest because of its prevalence. HPV and *Chlamydia trachomatis* are commonsexually transmittedinfections that couldbe associated with infertility.

Infection with HPV has been identified as one of the possible causes associated with male infertility, although the mechanisms that may be using this virus are not yet clear. However, it was found that HPV can act both at conception and gestational development. Although there are different places where HPV may be infecting, as mentioned in the first section, the main

Other studies confirm this last statement which demonstrates a significant reduction in sperm motility while other parameters were not affected (semen volume, pH, normal morphology, viability, sperm concentration) [49] and cell desquamation. Sperm infected by HPV can go on to introduce the virus to the oocyte when being fertilized, which can have different conse‐ quences such as underdevelopment of the fetus. It has been observed that couples undergoing *in vitro* fertilization and abortion are at high risk of HPV from semen samples [18]. Therefore, diagnosis of HPV should be included in the diagnosis of infertility especially when considering

cancer and precancerous lesions [45, 46].

74 Genital Infections and Infertility

*trachomatis* with HSV (types 1 and 2) was 9.6 % [48].

know how each of these pathogens affects infertility.

concern linked to infertility is regarding the quality of sperm [18].

cases of pregnancy loss [20] (Figure 2).

**quality**

Currently, molecular techniques have detected HPV in different samples (i.e. semen, scrape of the epithelium in different parts of the masculine reproductive apparatus) in heterosexual men with a maximum prevalence of 21 % [50]. Another molecular technique, fluorescent *in situ* hybridization has allowed location of HPV on the sperm head and on the surface of sperm cells. The presence of the virus on the surface of sperm suggests that glycosaminoglycans, or soluble factors similar in chemical structure, could be involved in the binding of the sperm and HPV [49, 51]. Another study demonstrated that glycosaminoglycans syndecan-1 protein may be the unifying factor, particularly HPV L1 capsid protein because it has been unable to locate these two molecules in the sperm head [18]. We suggest that this may be a feature that explains infertility due to the fact that HPV on the head of the sperm, and on its surface, may prevent entry of the sperm to the egg because of steric hindrance since receivers can be occupied by HPV. On the other hand if fertilization is accomplished then infection of the embryo may occur. HPV in this manner could affect male fertility and that of the couple.

Despite this evidence understanding has not been achieved fully regarding the role of HPV in male infertility so the study of *Chlamydia trachomatis* as a co-factor was suggested.

With respect to *Chlamydia trachomatis* they have been reported in several studies as a major cause of female infertility [52, 53, 54]. However, male infertility has not been investigated as thoroughly.

*Chlamydia trachomatis*, as a sexually transmitted disease, is suggested as a factor that may be involved in the infertility of the couple. Recent studies have shown that *Chlamydia trachoma‐ tis* infection has shown an important role in chronic prostatitis [55] that could allow *Chlamydia trachomatis* to move to different areas of the male reproductive system allowing the infection to reach areas of sperm production.

It has been suggested that the cause of apoptosis of sperm is the lipopolysaccharide of the *Chlamydia* cell wall [56, 57] (Figure 2). This effect is even more serious because it would kill the sperm, preventing fertilization due to a lack of sperm, giving the bacteria a central role in male infertility.

There is little research studying the effect of these two infections as co-factors in regard to male infertility. In a study of men from Denmark it was reported that *Chlamydia trachomatis*infection may be a risk factor that allows the acquisition of an additional type of a genotype of HPV [57]. In a multivariate analysis, it was found that infection with *Chlamydia trachomatis* is significantly associated with HPV [59].

It is proposed that co-factors such as genital tract infections could have an important role in the evolution and outcome of HVP. For example, the association of HVP with *Chlamydia trachomatis* could be associated with increased risk of cervical cancer and with the reduction in cell mediated immunity [60]. This was reported in the cervix, but the same could be happening in the male reproductive system. Therefore, *Chlamydia trachomatis* infection could be a predisposing factor for the acquisition of HPV factor, which becomes more relevant if we consider that more than 50% of *Chlamydia trachomatis* infections are asymptomatic in men [61]. It has been observed that men with *Chlamydia trachomatis* infection are at increased risk of contracting an HPV infection [47].

In a study, it was found that heterosexual men, with prostatitis symptoms attributable to *Chlamydia trachomatis* and with papillomavirus had a lower motile sperm motility. Also, the morphology was lower compared with patients that were infected only with *Chlamydia trachomatis.* However, the results did not show any significant relationship depending on the HPV genotype presented [62].

Both HPV and *Chlamydia trachomatis* are sexually transmitted infections that have become important because of their prevalence, and it has been suggested that their association may be related to the development of other complications, as in the case of sperm quality.

In conclusion, the presence of *Chlamydia trachomatis* plays an important role in male infertility as well as sperm production and also facilitates entry of HPV, which contributes to a large degree the affectation of sperm. Therefore, HPV and *Chlamydia trachomatis*, and their associa‐ tions, are two important pathogens that should be included in diagnostic tests for male infertility and the infertility of couples.
