Lang Tali, Dechant Maria, Sanchez Victoria, Wistuba Joachim, Boiani Michele, Pilatz Adrian, Stammler Angelika, Middendorff Ralf, Schuler Gerhard, Bhushan Sudhanshu, Tchatalbachev Svetlin, Wübbeling Frank, Burger Martin, Chakraborty Trinad, Mallidis Con, Meinhardt Andreas
Department of Anatomy and Cell Biology, Justus-Liebig-University Giessen, Germany.
Biol Reprod. 2013 Sep 19;89(3):59. doi: 10.1095/biolreprod.113.110379. Print 2013 Sep.
Uropathogenic Escherichia coli (UPEC)-associated epididymitis is commonly diagnosed in outpatient settings. Although the infection can be successfully cleared using antimicrobial medications, 40% of patients unexplainably show persistent impaired semen parameters even after treatment. Our aim was to investigate whether pathogenic UPEC and its associated virulence factor hemolysin (hlyA) perturb the structural and functional integrity of both the epididymis and sperm, actions that may be responsible for the observed impairment and possibly a reduction of fertilization capabilities. Semen collected from patients diagnosed with E. coli-only related epididymitis showed that sperm counts were low 14 days postantimicrobial treatment regardless of hlyA status. At Day 84 following treatment, hlyA production correlated with approximately 4-fold lower sperm concentrations than in men with hlyA-negative strains. In vivo experiments with the hlyA-producing UPEC CFT073 strain in a murine epididymitis model showed that just 3 days postinfection, structural damage to the epididymis (epithelial damage, leukocyte infiltration, and edema formation) was present. This was more severe in UPEC CFT073 compared to nonpathogenic E. coli (NPEC 470) infection. Moreover, pathogenic UPEC strains prematurely activated the acrosome in vivo and in vitro. Raman microspectroscopy revealed that UPEC CFT073 undermined sperm integrity by inducing nuclear DNA damage. Consistent with these observations, the in vitro fertilization capability of hlyA-treated mouse sperm was completely abolished, although sperm were motile. These findings provide new insights into understanding the possible processes underlying clinical manifestations of acute epididymitis.
与尿路致病性大肠杆菌（UPEC）相关的附睾炎通常在门诊环境中被诊断出来。尽管使用抗菌药物可以成功清除感染，但40%的患者在治疗后精液参数仍出现无法解释的持续受损。我们的目的是研究致病性UPEC及其相关毒力因子溶血素（hlyA）是否会破坏附睾和精子的结构及功能完整性，这些作用可能是导致观察到的损害以及可能的受精能力下降的原因。从仅被诊断为大肠杆菌相关性附睾炎的患者收集的精液显示，无论hlyA状态如何，抗菌治疗14天后精子计数都很低。在治疗后的第84天，与携带hlyA阴性菌株的男性相比，hlyA的产生与精子浓度低约4倍相关。在小鼠附睾炎模型中对产生hlyA的UPEC CFT073菌株进行的体内实验表明，感染后仅3天，附睾就出现了结构损伤（上皮损伤、白细胞浸润和水肿形成）。与非致病性大肠杆菌（NPEC 470）感染相比，UPEC CFT073感染的情况更严重。此外，致病性UPEC菌株在体内和体外都会过早激活顶体。拉曼光谱显示，UPEC CFT073通过诱导核DNA损伤破坏了精子的完整性。与这些观察结果一致，尽管精子有活力，但经hlyA处理的小鼠精子的体外受精能力完全丧失。这些发现为理解急性附睾炎临床表现背后的可能过程提供了新的见解。
