Rojas-Barón Lisbeth, Tana-Hernandez Leandro, Nguele Ampama Mireille H, Sanchéz Raúl, Gärtner Ulrich, Wagenlehner Florian M E, Preußer Christian, Pogge von Strandmann Elke, Hermosilla Carlos, Taubert Anja, Francia María E, Velasquez Zahady D
Institute of Parasitology, Justus Liebig University Giessen, Germany.
Laboratory of Apicomplexan Biology, Institut Pasteur de Montevideo, Uruguay.
FEBS J. 2025 Sep;292(17):4720-4736. doi: 10.1111/febs.70097. Epub 2025 May 3.
Toxoplasma gondii is an obligate intracellular protozoan parasite that can infect virtually any nucleated cell within human and other endoderm animal tissue, including male reproductive organs. Herein, we investigate the capacity of T. gondii tachyzoites to infect and proliferate within the testes and epididymis and examine the resulting impact on human spermatozoa structure and functionality. We confirmed that T. gondii tachyzoites colonise and proliferate within the testes and epididymis, altering the tissue structural homeostasis, and causing immune cell infiltration and cellular damage. In addition to demonstrating that T. gondii remains infective within the testes and epididymis, in vitro experiments demonstrated a direct interaction between T. gondii tachyzoites and human spermatozoa. This resulted in a significant proportion of headless spermatozoa. Scanning and transmission electron microscopy revealed structural defects in spermatozoa, such as twisted tails and plasma membrane disruptions. Moreover, T. gondii tachyzoites triggered the loss of mitochondrial membrane potential (MMP) in spermatozoa without modulating reactive oxygen species (ROS) concentrations, and triggered cell death, pointing at mitochondrial dysfunction as a potential mechanism mediating spermatozoan damage. Our findings suggest that T. gondii infection can have profound implications for male fertility by directly damaging spermatozoa and altering testicular and epididymal structures. The study underscores the need for further research to elucidate the long-term impact of T. gondii on male reproductive health, particularly in the context of iatrogenic infertility. Given the widespread seroprevalence of T. gondii in the human population, our research emphasises the importance of considering parasitic infections in diagnosing and managing male infertility in the field of andrology.
刚地弓形虫是一种专性细胞内原生动物寄生虫，几乎可以感染人类和其他内胚层动物组织内的任何有核细胞，包括男性生殖器官。在此，我们研究了刚地弓形虫速殖子在睾丸和附睾内感染和增殖的能力，并考察了其对人类精子结构和功能的影响。我们证实，刚地弓形虫速殖子在睾丸和附睾内定植并增殖，改变组织结构稳态，导致免疫细胞浸润和细胞损伤。除了证明刚地弓形虫在睾丸和附睾内仍具感染性外，体外实验还证明了刚地弓形虫速殖子与人类精子之间存在直接相互作用。这导致了相当比例的无头精子。扫描电子显微镜和透射电子显微镜显示精子存在结构缺陷，如尾部扭曲和质膜破裂。此外，刚地弓形虫速殖子在不调节活性氧（ROS）浓度的情况下引发精子线粒体膜电位（MMP）丧失，并引发细胞死亡，表明线粒体功能障碍是介导精子损伤的潜在机制。我们的研究结果表明，刚地弓形虫感染可通过直接损伤精子以及改变睾丸和附睾结构对男性生育能力产生深远影响。该研究强调需要进一步开展研究，以阐明刚地弓形虫对男性生殖健康的长期影响，尤其是在医源性不育的背景下。鉴于刚地弓形虫在人群中的血清流行率很高，我们的研究强调了在男科领域诊断和管理男性不育症时考虑寄生虫感染的重要性。
