Male infertility: a public health issue caused by sexually transmitted pathogens

Nature Reviews Urology:

 

Sexually transmitted diseases caused by bacteria, viruses and protozoa can affect the male genital tract. Gimenes and colleagues discuss the evidence for effects of sexually transmitted pathogens on semen, sperm and male infertility.

 

Fabrícia Gimenes,^1, Raquel P. Souza,^1, Jaqueline C. Bento,^3, Jorge J. V. Teixeira,^2, Silvya S. Maria-Engler,^4, Marcelo G. Bonini^5, & Marcia E. L. Consolaro^1,

 

Published online: 21 October 2014

 

Abstract:

 

Sexually transmitted diseases (STDs) are caused by several pathogens, including bacteria, viruses and protozoa, and can induce male infertility through multiple pathophysiological mechanisms. Additionally, horizontal transmission of STD pathogens to sexual partners or vertical transmission to fetuses and neonates is possible. Chlamydia trachomatis, Ureaplasma spp., human papillomavirus, hepatitis B and hepatitis C viruses, HIV-1 and human cytomegalovirus have all been detected in semen from symptomatic and asymptomatic men with testicular, accessory gland and urethral infections. These pathogens are associated with poor sperm quality and decreased sperm concentration and motility. However, the effects of these STD agents on semen quality are unclear, as are the effects of herpes simplex virus type 1 and type 2, Neisseria gonorrhoeae, Mycoplasma spp., Treponema pallidum and Trichomonas vaginalis, because few studies have evaluated the influence of these pathogens on male infertility. Chronic or inadequately treated infections seem to be more relevant to infertility than acute infections are, although in many cases the exact aetiological agents remain unknown.

 

Key points 

• Sexually transmitted diseases (STDs) can induce male infertility through multiple pathophysiological mechanisms
• Several STD-causing agents, including bacteria, viruses and protozoa have been detected in semen from symptomatic and asymptomatic males, and can be transmitted through natural intercourse or insemination
• STD pathogens can affect sperm parameters and functions, particularly when testicular, accessory gland and urethral infections localize the disease agents in proximity to semen
• Several highly sensitive and specific molecular methods are now available to explore the relationship between infertility and infections of semen with STD pathogens
• Chlamydia trachomatis, Ureaplasma spp., human papillomavirus, hepatitis B and C viruses, HIV-1 and human cytomegalovirus are associated with reduced sperm quality, concentration

Introduction

 

Sexually transmitted diseases (STDs) are caused by microorganisms that colonize the female and male genital tracts, often causing only mild symptoms.¹ STDs affect health and cause social and economic problems worldwide.^{2, 3} Despite the development of antibiotics and vaccines, and the existence of disease prevention and control programmes, these pathogens remain important causes of acute and chronic disease.¹

 

In 2000, the WHO recognized the role of genital tract infections in human infertility.⁴ STDs in men cause genital injury, infections of semen, prostatitis, urethritis, epididymitis and orchitis.⁵ Several studies have reported that infertile men are affected by semen infection,⁶ mainly resulting from testicular, accessory gland and urethral infections. Semen infection also has possible involvement in pregnancy complications and, via maternal infection, in transmission of pathogenic agents to the fetus or neonate.¹ STD-causing microorganisms detected in semen have been associated with poor sperm quality,⁷ decreases in sperm concentration and motility^{8, 9} and changes in other semen parameters relevant to fertility, including sperm velocity, morphology and viability, as well as seminal volume, pH, viscosity and biochemical composition.^{7, 8, 9}

 

Several STD pathogens have been detected in semen from asymptomatic and symptomatic men (Figure 1 and Table 1).^{10, 11, 12, 13, 14} Chronic or inadequately treated infections seem to have greater association with infertility than acute infections do, although in many cases the exact aetiological agents resulting in infertility remain unknown.¹ Undiagnosed, asymptomatic infections could have important implications for individual and public health.¹⁵

 

Figure 1: Major sexually transmitted disease pathogens detected in semen.

Inflammatory processes triggered in the male genital tract (MGT) by some STDs can lead to deterioration of spermatogenesis and obstruction of the seminal tract,^{16, 17} which can worsen the characteristics of semen (Figure 2 and Table 2).¹⁸ Abortive apoptosis is an important part of the control of spermatogenesis, and has been observed in spermatogonia, spermatocytes, spermatids and ejaculated spermatozoa.^{18, 19, 20} However, sperm apoptosis can also be associated with inflammatory conditions and oxidative stress that occur in response to infection, resulting in impaired motility and reduced capacity of spermatozoa for fertilization.^{18, 19, 20, 21, 22}

Figure 2: Sexually transmitted disease loci in the male genital tract and their relation to infertility.

The demonstration of a microorganism in the male genital tract and seminal fluid can be a sign of an infection with pathological sequelae. The inflammatory processes triggered by infection with some pathogens can lead to deterioration of spermatogenesis and obstruction of the seminal tract.

Over the past three decades, diagnostics for STDs have depended on traditional methods, such as bacterial culture, enzyme immunoassays, fluorescent antibody staining and microscopy. In recent years, several highly sensitive and specific PCR-based diagnostic methods have become available, enabling better understanding of the relationship between infertility and infections of semen with STD pathogens.²³

Figure 3: Interaction of sexually transmitted disease pathogens with spermatogenic cells and spermatozoa.

a | Schematic diagram and representative photomicrographs (with Leishman staining) of spermatogenesis, indicating pathogens that are known to attach and internalize in spermatogenic cells. b | Photomicrograph indicating sperm death by staining (red) with eosin-nigrosin, and schematic illustration of a spermatozoon showing sites of attachment and internalization of sexually transmitted disease pathogens. Internalization in the sperm head can cause DNA damage.