Structural and functional integrity of spermatozoa is compromised as a consequence of acute uropathogenic E. Coli-associated epididymitis

Tali Lang, Maria Dechant, Victoria Sanchez, Joachim Wistuba, Michele Boiani, Adrian Pilatz, Angelika Stammler, Ralf Middendorff, Gerhard Schuler, Sudhanshu Bhushan, Svetlin Tchatalbachev, Frank Wübbeling, Martin Burger, Trinad Chakraborty, Con Mallidis, Andreas Meinhardt

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19 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number59
JournalBiology of Reproduction
Volume89
Issue number3
DOIs
Publication statusPublished - 2013
Externally publishedYes

Keywords

  • Acrosome reaction
  • Bacterial epididymitis
  • Epididymis
  • Male infertility
  • Sperm DNA fragmentation

Cite this

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. / Structural and functional integrity of spermatozoa is compromised as a consequence of acute uropathogenic E. Coli-associated epididymitis. In: Biology of Reproduction. 2013 ; Vol. 89, No. 3.
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title = "Structural and functional integrity of spermatozoa is compromised as a consequence of acute uropathogenic E. Coli-associated epididymitis",
abstract = "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.",
keywords = "Acrosome reaction, Bacterial epididymitis, Epididymis, Male infertility, Sperm DNA fragmentation",
author = "Tali Lang and Maria Dechant and Victoria Sanchez and Joachim Wistuba and Michele Boiani and Adrian Pilatz and Angelika Stammler and Ralf Middendorff and Gerhard Schuler and Sudhanshu Bhushan and Svetlin Tchatalbachev and Frank W{\"u}bbeling and Martin Burger and Trinad Chakraborty and Con Mallidis and Andreas Meinhardt",
year = "2013",
doi = "10.1095/biolreprod.113.110379",
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Lang, T, Dechant, M, Sanchez, V, Wistuba, J, Boiani, M, Pilatz, A, Stammler, A, Middendorff, R, Schuler, G, Bhushan, S, Tchatalbachev, S, Wübbeling, F, Burger, M, Chakraborty, T, Mallidis, C & Meinhardt, A 2013, 'Structural and functional integrity of spermatozoa is compromised as a consequence of acute uropathogenic E. Coli-associated epididymitis', Biology of Reproduction, vol. 89, no. 3, 59. https://doi.org/10.1095/biolreprod.113.110379

Structural and functional integrity of spermatozoa is compromised as a consequence of acute uropathogenic E. Coli-associated epididymitis. / 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.

In: Biology of Reproduction, Vol. 89, No. 3, 59, 2013.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Structural and functional integrity of spermatozoa is compromised as a consequence of acute uropathogenic E. Coli-associated epididymitis

AU - Lang, Tali

AU - Dechant, Maria

AU - Sanchez, Victoria

AU - Wistuba, Joachim

AU - Boiani, Michele

AU - Pilatz, Adrian

AU - Stammler, Angelika

AU - Middendorff, Ralf

AU - Schuler, Gerhard

AU - Bhushan, Sudhanshu

AU - Tchatalbachev, Svetlin

AU - Wübbeling, Frank

AU - Burger, Martin

AU - Chakraborty, Trinad

AU - Mallidis, Con

AU - Meinhardt, Andreas

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

KW - Acrosome reaction

KW - Bacterial epididymitis

KW - Epididymis

KW - Male infertility

KW - Sperm DNA fragmentation

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U2 - 10.1095/biolreprod.113.110379

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M3 - Article

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JO - Biology of Reproduction

JF - Biology of Reproduction

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