Dvorakova-Hortova Katerina, Sidlova Adela, Ded Lukas, Hladovcova Denisa, Vieweg Markus, Weidner Wolfgang, Steger Klaus, Stopka Pavel, Paradowska-Dogan Agnieszka
Biocev Group, Department of Zoology, Faculty of Science, Charles University in Prague, Prague, Czech Republic.
Laboratory of Reproductive Biology, Institute of Biotechnology, Academy of Science, Prague, Czech Republic.
PLoS One. 2014 Jun 18;9(6):e96770. doi: 10.1371/journal.pone.0096770. eCollection 2014.
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.
弓形虫是一种常见的原生动物寄生虫，可感染包括小鼠和人类在内的全球温血动物。在感染过程中，寄生虫和宿主都会利用各种机制来最大化自身的繁殖成功率。小鼠和人类都是弓形虫的中间宿主，弓形虫会在前者的组织中形成含有生殖囊肿的特殊液泡。由于全球有一半人口受到感染，并患上一种名为弓形虫病的疾病，同时越来越多的夫妇患有特发性不孕症，因此令人惊讶的是，关于弓形虫如何改变生殖参数的研究却很少。在这项研究中，对感染小鼠的睾丸功能进行了详细的组织计量学筛查，并分析了垂体促黄体生成素（LH）的水平。还收集了有关相对睾丸和附睾重量以及精子数量的数据。根据获得的结果，与对照组相比，弓形虫感染小鼠尿液中的LH水平较低。以精子数量和组织计量学分析为指标，在弓形虫阳性组中，睾丸功能和精子生成也与激素水平直接相关，显著降低。不仅细线期初级精母细胞和精子细胞的数量减少，而且支持细胞的数量和小管直径增加。同时，对睾丸整体甲基化以及成功进行精子发生所必需的Crem、Creb1和Hspa1基因的特定甲基化进行了一项初步的表观遗传学研究。弓形虫感染小鼠的整体甲基化升高，并且在弓形虫阳性组和对照组之间检测到所选基因的DNA甲基化存在差异。这些发现表明弓形虫感染与小鼠雄性生殖适应性下降之间存在直接关系，这可能导致人类特发性不孕症的增加。
