Risk to male fertility: Common parasite Toxoplasma gondii found to decapitate human sperm

After only five minutes of direct contact between Toxoplasma gondii tachyzoites and sperms, 22.4% of spermatozoa were headless, compared with just 1.6% in controls. By 10 minutes, the proportion of headless sperm became fourfold relative to controls, and by 15 minutes, it had increased eightfold. Many sperm developed twisted, rolled, or shortened tails, impairing their motility

Toxoplasma gondii is a protozoan parasite found across the globe and infects up to a third of the world’s population. That the parasite can infect virtually any nucleated cell in humans was already known. Now the parasite has been shown to cause infection within the testes, impacting the structure and function of human sperm.

An international team found that after just five minutes of coming into direct contact with the parasite 22% of the studied spermatozoa were headless when compared to the control group. The findings were published in the FEBS Journal.

How humans get infected

T. gondii’s life cycle revolves around felines, including domestic cats, which are their definitive hosts. Cats excrete the unsporulated oocysts or the immature, non-infectious stage of the parasite. In the environment, these oocysts sporulate or develop and mature to form spores, making them infectious. Humans get infected by the parasite from cat faeces, unwashed or contaminated produce, or by eating undercooked meat containing the oocysts.

Most infections go unnoticed. Healthy individuals typically experience no symptoms or only mild, flu-like illness. The parasite lies dormant in the brain, muscles, eyes or lungs for years by forming tissue cysts containing slow-replicating bradyzoites. But in immunocompromised patients, toxoplasmosis can cause brain inflammation, eye disease, and widespread infection affecting multiple organs.

T. gondii can also cross the placental barrier be transmitted vertically from mother to foetus, leading to miscarriage or congenital defects. Now, researchers have added men’s reproductive health to the list of concerns.

Crossing the blood-testes barrier

The team investigated the capacity of T. gondii tachyzoites (highly motile stage of the parasite) to infect and proliferate within the testes. Eight-week-old male mice were infected with T. gondii tachyzoites, and six days after the infection, the mice were sacrificed and tissue samples from the epididymis (a narrow, tightly-coiled tube attached to each of the testicles where sperm is stored) and testicles were studied. The researchers found that T. gondii tachyzoites colonise and proliferate within the testes and epididymis. T. gondii cysts can also reside in the testes of mice for at least four weeks post-infection. The presence of cysts in the testes of mice was previously found to correlate with lower testes weight, sperm count and motility, as well as increased abnormal sperm morphology.

T. gondii has been previously shown to cross barriers, such as the blood-brain barrier and the placental barrier. However, the underlying mechanisms and consequences of T. gondii crossing the blood-testes barrier have not been fully studied. Other studies have previously shown that the parasite can cross the blood-testes barrier of rats and the ejaculate from T. gondii-infected rats not only displayed the presence of viable tachyzoites but also male rats were able to infect females through sex. In rats, the effects of toxoplasmosis — infection by T. gondii — on sperm count, motility and morphology have been studied.

Decapitating sperm

Sexual transmission of T. gondii in humans has not been studied so far. However, based on a higher prevalence of toxoplasmosis in infertile men, a May 2021 study found that 27% of men with semen pathologies and 22.3% of those with normozoospermia tested seropositive for T. gondii. Importantly, about 86.6% of T. gondii-positive men exhibited semen abnormalities, including low sperm count, reduced sperm motility, and higher prevalence of abnormally shaped sperm. However, the May 2021 study did not find any evidence that the parasite affects sperm morphology.

In order to better understand the impact of T. gondii tachyzoites on human sperm, the researchers of the latest study collected human semen samples from 30 healthy volunteer donors (aged between 20 and 38 years) with informed written consent. Scanning electron microscopic analysis was performed on the human sperm after 10 minutes of direct contact with the T. gondii tachyzoites.

After only five minutes of contact, 22.4% of spermatozoa were headless, compared with just 1.6% in controls. By 10 minutes, the proportion of headless sperm became fourfold relative to controls, and by 15 minutes, it had increased eightfold. Many sperm developed twisted, rolled, or shortened tails, impairing their motility. Microscopy studies revealed holes, cracks, and surface irregularities in sperm heads. The present work carried out all experiments using only mature human sperm.

The team tested whether molecules secreted by the parasite, or exosomes, could produce the same effect. They did not. Only direct, physical contact between parasite and sperm triggered decapitation.

As spermatozoa depend on mitochondrial ATP-derived energy for motility, the team looked at sperm mitochondria. They found that T. gondii tachyzoites triggered the loss of mitochondrial membrane potential. The team notes that mitochondrial dysfunction could be a potential mechanism mediating the spermatozoan damage.

So what was the exact mechanism behind this decaptiation? Zahady D. Velasquez from the Institute of Parasitology, Justus Liebig University Giessen, Giessen, Germany, and the corresponding author of the paper, said in an email: “The presence of the tachyzoite seems to be fundamental to beheaded human sperm. However, we are currently working on the mechanism. I hope we will be able to deliver more information about it during the next year.” She added that they have only tested the RH strain of the parasite and are currently working on experiments with other strains.

It is not clear at this point in time if the infection-induced sperm defects are reversible after antiparasitic treatment or are they likely permanent. “I don´t have comments on it because we don´t know yet the mechanism associated with sperm decapitation. This is something that we will analyse further after having more mechanistic information,” Dr Velasquez said in the email.  

What that means for male fertility

If replicated in vivo, the findings could have major implications for understanding male infertility. The World Fertility 2024 report by the United Nations Department of Economic and Social Affairs, Population Division, notes that “The global fertility rate is projected to continue to decline, reaching the replacement level of 2.1 in 2050 and falling further to 1.8 births per woman in 2100.”

The researchers conclude that: “Given that chronic toxoplasmosis prevalence ranges between 1% and 100% in the global human population, depending on geographical location, and the presence of cysts in human testes has been documented, reactivation of these cysts into fast-replicating tachyzoites could have an underappreciated impact on male fertility.”