Abstract
Toxoplasma gondii is a common protozoan parasite that infects warm-blooded animals throughout the world, including mice and humans. During infection, both, the parasite and the host, utilize various mechanisms to maximize their own reproductive success. Mice and humans are both the intermediate hosts for Toxoplasma gondii, which forms specialized vacuoles containing reproductive cysts in the formers’ tissue. As half of the human population is infected, developing a disease called toxoplasmosis, along with an ever-growing number of couples suffering with idiopathic infertility, it is therefore surprising that there is a lack of research on how Toxoplasma gondii can alter reproductive parameters. In this study, a detailed histometric screening of the testicular function along with the levels of the pituitary luteinizing hormone (LH) were analysed in infected mice. Data on relative testis and epididymis weight, and sperm count were also collected. Based on the results obtained, the level of LH in the urine of Toxoplasma gondii infected mice was lower compared to the control. In direct correlation with the hormone level, testicular function and sperm production was also significantly lower in Toxoplasma gondii positive group using sperm count and histometric analysis as a marker. Not only were the number of leptotene primary spermatocytes and spermatids lowered, but the number of Sertoli cells and the tubule diameter were elevated. In parallel, a pilot epigenetic study on global testicular methylation, and specific methylation of Crem, Creb1 and Hspa1genes essential for successfully ongoing spermatogenesis was performed. Global methylation was elevated in Toxoplasma infected mice, and differences in the DNA methylation of selected genes were detected between the Toxoplasma positive and control group. These findings demonstrate a direct relation between Toxoplasma gondii infection and the decrease of male reproductive fitness in mice, which may contribute to an increase of idiopathic infertility in humans.
Highlights
Toxoplasmosis, caused by the protozoan parasite Toxoplasma gondii (T. gondii), is one of the most common parasitic infections of man and other warm-blooded animals
In the second part of this work, we focused on testing global testicular methylation in the T. gondii positive and control group, and we analysed the specific methylation of three selected genes Crem, Creb1 and Hspa1, essential for successful spermatogenesis and at the same time being responsive to epigenetic regulation through DNA methylation
For the Toxo+ group, there was a statistically higher amount of Sertoli cells (17.6164.03 vs. 15.1563.22) and a larger tubule diameter (129.68632.02 vs. 125.78630.26) and at the same time a lower number of leptotene primary spermatocytes and spermatids compared to the Toxo2 group
Summary
Toxoplasmosis, caused by the protozoan parasite Toxoplasma gondii (T. gondii), is one of the most common parasitic infections of man and other warm-blooded animals. Most Toxoplasma strains isolated in North America and Europe belong to three clonal lines referred to as: Type I, II and III [3,4]. Type II and III avirulent strains cause nonlethal infections, characterized by the development of chronic latent infections of the CNS and skeletal muscles. Connections were made between Toxoplasma infection and the sperm quality in humans [6]. It was later documented [7] that there was a decreased fertility in rats after being infected with T. gondii along with a lower weight of epididymis, decreased sperm motility and concentration, and an increased number of abnormal sperm morphology. The correlation between toxoplasmosis and increased sperm apoptosis, especially of diploid spermatocytes, was described [8]
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