title: Toll-like receptors (TLR) 2 and 4 on human sperm recognize bacterial endotoxins and mediate apoptosis.
abstract: BACKGROUND
  Bacterial infections of the genital tract are one of the most serious causes of infertility in males. In some human patients with poor semen quality, leukocytospermia has been observed. Because leukocytes express the bacterial-lipopolysaccharide (LPS) responsive Toll-like receptor (TLR) signaling cascade and secrete tumor necrosis factor-α, secreted cytokines comprise one, but probably not the only, class of factors that can impact sperm motility.
  
  
  RESULTS
  In this study, we documented that bacterial endotoxins, LPS and peptidoglycan, can be detected in human semen. Furthermore, the addition of endotoxins in the absence of leukocytes directly and significantly reduced the motility and increased the apoptotic rate of both human and mouse sperm and suppressed fertilization by mouse sperm both in vivo and in vitro. The well-known LPS receptor, TLR4, and peptidoglycan receptor, TLR2, were expressed in human and mouse sperm. In Tlr2/4(-/-) double-mutant mice, the negative effects of endotoxins on sperm functions were blocked, suggesting that the bacterial endotoxins mediated activation of TLR-dependent pathways in sperm leading to apoptosis.
  
  
  CONCLUSIONS
  Sperm can recognize bacterial endotoxins by TLRs present in their membranes. The activated TLRs reduce sperm motility, induce sperm apoptosis and significantly impair the potential for fertilization.
authors.affiliation: Laboratory of Reproductive Endocrinology, Department of Applied Animal Science, Graduate School of Biosphere Science, Hiroshima University, Higashi-Hiroshima, Hiroshima 739-8528, Japan.
authors.forename: Youko
authors.initials: Y
authors.lastname: Fujita
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Mihara
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Okazaki
authors.forename: Manami
authors.initials: M
authors.lastname: Shitanaka
authors.forename: Rena
authors.initials: R
authors.lastname: Kushino
authors.forename: Chiaki
authors.initials: C
authors.lastname: Ikeda
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Negishi
authors.forename: Zhilin
authors.initials: Z
authors.lastname: Liu
authors.forename: JoAnne S
authors.initials: JS
authors.lastname: Richards
authors.forename: Masayuki
authors.initials: M
authors.lastname: Shimada
mesh_terms: D000818:Animals; D017209:Apoptosis; D016207:Cytokines / Q000096:biosynthesis; D004731:Endotoxins / Q000378:metabolism*; D006801:Humans; D007248:Infertility, Male / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides / Q000378:metabolism; D008297:Male; D052801:Male Urogenital Diseases / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D010457:Peptidoglycan / Q000378:metabolism; D015398:Signal Transduction; D013094:Spermatozoa / Q000378:metabolism* / Q000473:pathology; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis*; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D016207:Cytokines; D004731:Endotoxins; D008070:Lipopolysaccharides; D010457:Peptidoglycan; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha