Infertility affects an estimated 15% of the global population, and male factors contribute to 40%-50% of cases. Increasing evidence suggests that exposure to toxins and pollutants affects spermatogenesis and contributes to a decline in male reproductive health.

Researchers from the Institute of Environmental Assessment and Water Research, Barcelona, Spain; Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement, Paris, France; and Universitat Rovira i Virgili, Tarragona, Spain, conducted a study that evaluated the chemical exposome (the set of toxic chemical substances to which the population is exposed) in urine, blood, and semen samples from young, apparently healthy men. The findings were published in Exposome.

Study Design

To assess potentially harmful nonvolatile organic compounds that could affect spermatogenesis, researchers analyzed semen, blood, and urine samples from 48 men aged 18-40 years, most of whom resided in Tarragona, Spain.

The exclusion criteria were as follows: major chronic disease; reproductive disorders; organ transplantation; cardiovascular disease; HIV or hepatitis B or C infection; active or recent cancer; severe psychiatric or endocrine disorders; hepatic insufficiency; use of medications such as antidepressants, corticosteroids, or immunosuppressants; recent substantial weight loss; and any condition that could impair adherence to the protocol.

Speaking with Univadis Spain, part of the Medscape Professional Network, Montse Marquès Bueno, PhD, the study’s first author, said, “The fact that most of the participants resided in Tarragona was not an inclusion criterion in itself. The reason is that recruitment was carried out by Rovira i Virgili University and that sample collection had to be done in Tarragona. The reason for this requirement is that the semen samples had to be delivered for preservation, at most, 1 hour after ejaculation.”

Researchers have evaluated exposure to more than 2000 nonvolatile organic compounds using a broad-spectrum screening approach. The analysis identified 42 substances in semen, 42 in urine, and 48 in the blood. The detected compounds included artificial sweeteners, insecticides, per- and polyfluoroalkyl substances, flame retardants, food-related compounds, pharmaceuticals, tire wear particles, and markers of tobacco exposure.

Although previous studies have examined toxic exposures in the blood and urine, few have analyzed semen because of the challenges associated with sample handling and preservation. A distinguishing feature of this study was the use of high-resolution mass spectrometry, which enabled the identification of nonvolatile organic compounds with a mass accuracy of less than 0.001 atomic mass units.

This precision allows researchers to distinguish between chemically similar substances. “It is important to note that we analyzed only the presence of nonvolatile organic compounds, which exclude other substances that can significantly affect reproductive health, such as heavy metals and volatile organic compounds. This is particularly relevant in Tarragona because of the presence of a large petrochemical complex. High-resolution mass spectrometry does not allow the analysis of these types of compounds, and other techniques would be required,” Marquès said.

However, the use of this technique has allowed researchers to go a step further than most studies of this type. “Traditionally, studies examining toxins in biological matrices focus on specific families of compounds. In this work, however, we used a broad screening approach capable of detecting approximately 2000 compounds simultaneously across three biological matrices: semen, blood, and urine.”

However, the ability to simultaneously search for numerous compounds across multiple matrices has drawbacks. “The high cost associated with analyzing each sample meant that we could analyze samples from only 48 of the 200 participants.”

Associations With Semen Quality

Several detected compounds were inversely associated with semen quality parameters, such as sperm motility, concentration, morphology, and volume.

For example, acesulfame, an artificial sweetener; bisphenol S, which is used in plastics and resins; the insecticide nitenpyram; and certain industrial and pharmaceutical surfactants were negatively associated with total sperm count, morphology, and concentration. Triethyl phosphate, a flame retardant, was associated with a lower semen volume. Additives used in tire manufacturing have been linked to reduced motility and vitality.

This study also confirmed previously reported negative associations for tobacco-derived compounds, including nicotine and cotinine, and persistent perfluorinated compounds used in cookware, packaging, and textiles.

“This supports the validity of our study because if we identify associations that have already been widely reported, the novel associations we detected are also likely to be valid. This is particularly important because our study had limited statistical power, given that data were available from only 48 individuals,” Marquès said.

These findings add to the evidence that cumulative exposure to nonvolatile organic compounds may adversely affect spermatogenesis and contribute to declining male fertility.

“Our study does not allow us to establish causal relationships between the presence of multiple nonvolatile organic compounds and spermatogenesis. However, there is an association between exposure to these compounds and semen quality. We plan to continue this research; samples from more than 150 additional men have been stored but not yet analyzed, and we now need funding to proceed,” Marquès concluded.

The authors reported having no relevant conflicts of interest.

This story was translated from Univadis Spain.