Toxoplasma gondii decreases the reproductive fitness in mice

PLoS One. 2014 Jun 18;9(6):e96770. doi: 10.1371/journal.pone.0096770. eCollection 2014.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CpG Islands
  • Cyclic AMP Response Element Modulator / genetics
  • Cyclic AMP Response Element Modulator / metabolism
  • Cyclic AMP Response Element-Binding Protein / genetics
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • DNA Methylation
  • Epididymis / metabolism
  • Epididymis / parasitology*
  • Epididymis / pathology
  • Epigenesis, Genetic
  • Gene Expression
  • Genetic Fitness / genetics*
  • HSP70 Heat-Shock Proteins / genetics
  • HSP70 Heat-Shock Proteins / metabolism
  • Host-Parasite Interactions
  • Humans
  • Luteinizing Hormone / genetics
  • Luteinizing Hormone / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Oligospermia
  • Seminiferous Tubules / metabolism
  • Seminiferous Tubules / parasitology*
  • Seminiferous Tubules / pathology
  • Sertoli Cells / metabolism
  • Sertoli Cells / parasitology*
  • Sertoli Cells / pathology
  • Spermatozoa / metabolism
  • Spermatozoa / pathology
  • Toxoplasma / pathogenicity*
  • Toxoplasma / physiology
  • Toxoplasmosis, Animal / genetics
  • Toxoplasmosis, Animal / metabolism
  • Toxoplasmosis, Animal / parasitology
  • Toxoplasmosis, Animal / pathology*

Substances

  • Creb1 protein, mouse
  • Crem protein, mouse
  • Cyclic AMP Response Element-Binding Protein
  • HSP70 Heat-Shock Proteins
  • Cyclic AMP Response Element Modulator
  • Luteinizing Hormone

Grants and funding

The work was supported by the Institutional Research Support grant No. SVV 260 087/2014, by the Grant Agency of the Czech Republic GACR No. P506/12/1046 and by the project „BIOCEV – Biotechnology and Biomedicine Centre of the Academy of Sciences and Charles University“ (CZ.1.05/1.1.00/02.0109), from the European Regional Development Fund. Founding for methylation analysis was provided from LOEWE focus group MIBIE (“Male Infertility during Infection and Inflammation” projects state government of Hessen, Germany). The funders had no influence on study design, data collection and analysis, decision to publish, or preparation of the manuscript.