Toll-like Receptors (TLR) 2 and 4 on Human Sperm Recognize Bacterial Endotoxins and Mediate Apoptosis

Overview

Journal Hum Reprod

Publisher Oxford University Press

Specialty Reproductive Medicine

Date 2011 Jul 22

PMID 21775336

Citations 51

Authors

Youko Fujita

Toshihiro Mihara

Tetsuji Okazaki

Manami Shitanaka

Rena Kushino

Chiaki Ikeda

Hiroaki Negishi

Zhilin Liu

JoAnne S Richards

Masayuki Shimada

Affiliations

Soon will be listed here.

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.

Methods And 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.

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References

Diemer T, Ludwig M, Huwe P, Hales D, Weidner W . Influence of urogenital infection on sperm function. Curr Opin Urol. 2000; 10(1):39-44. DOI: 10.1097/00042307-200001000-00010. View

Ochsendorf F . Sexually transmitted infections: impact on male fertility. Andrologia. 2008; 40(2):72-5. DOI: 10.1111/j.1439-0272.2007.00825.x. View

Allam J, Fronhoffs F, Fathy A, Novak N, Oltermann I, Bieber T . High percentage of apoptotic spermatozoa in ejaculates from men with chronic genital tract inflammation. Andrologia. 2008; 40(5):329-34. DOI: 10.1111/j.1439-0272.2008.00864.x. View

Jiang D, Liang J, Fan J, Yu S, Chen S, Luo Y . Regulation of lung injury and repair by Toll-like receptors and hyaluronan. Nat Med. 2005; 11(11):1173-9. DOI: 10.1038/nm1315. View

Kawano N, Shimada M, Terada T . Motility and penetration competence of frozen-thawed miniature pig spermatozoa are substantially altered by exposure to seminal plasma before freezing. Theriogenology. 2003; 61(2-3):351-64. DOI: 10.1016/s0093-691x(03)00218-8. View

KILE Jr J . An improved method for the artificial insemination of mice. Anat Rec. 1951; 109(1):109-17. DOI: 10.1002/ar.1091090108. View

Saleh R, Agarwal A, Kandirali E, Sharma R, Thomas A, Nada E . Leukocytospermia is associated with increased reactive oxygen species production by human spermatozoa. Fertil Steril. 2002; 78(6):1215-24. DOI: 10.1016/s0015-0282(02)04237-1. View

Greenlee A, Banks K . Cellular and lipopolysaccharide subunit requirements for the caprine lymphoblastogenic response to endotoxin. Am J Vet Res. 1985; 46(1):75-9. View

Cardona-Maya W, Lopez-Herrera A, Velilla-Hernandez P, Rugeles M, Cadavid A . The role of mannose receptor on HIV-1 entry into human spermatozoa. Am J Reprod Immunol. 2006; 55(4):241-5. DOI: 10.1111/j.1600-0897.2005.00340.x. View

10.

Eley A, Pacey A, Galdiero M, Galdiero M, Galdiero F . Can Chlamydia trachomatis directly damage your sperm?. Lancet Infect Dis. 2004; 5(1):53-7. DOI: 10.1016/S1473-3099(04)01254-X. View

11.

Okazaki T, Mihara T, Fujita Y, Yoshida S, Teshima H, Shimada M . Polymyxin B neutralizes bacteria-released endotoxin and improves the quality of boar sperm during liquid storage and cryopreservation. Theriogenology. 2010; 74(9):1691-700. DOI: 10.1016/j.theriogenology.2010.05.019. View

12.

Anderson D, Hill J . Cell-mediated immunity in infertility. Am J Reprod Immunol Microbiol. 1988; 17(1):22-30. DOI: 10.1111/j.1600-0897.1988.tb00197.x. View

13.

Fraczek M, Kurpisz M . Inflammatory mediators exert toxic effects of oxidative stress on human spermatozoa. J Androl. 2006; 28(2):325-33. DOI: 10.2164/jandrol.106.001149. View

14.

Sullivan J, Elliott F, Bartlett D, Murphy D, Kuzdas C . Further studies on use of polymyxin B sulfate with dihydrostreptomycin and penicillin for control of Vibrio fetus in a frozen semen process. J Dairy Sci. 1966; 49(12):1569-71. DOI: 10.3168/jds.S0022-0302(66)88140-7. View

15.

Borini A, Tarozzi N, Bizzaro D, Bonu M, Fava L, Flamigni C . Sperm DNA fragmentation: paternal effect on early post-implantation embryo development in ART. Hum Reprod. 2006; 21(11):2876-81. DOI: 10.1093/humrep/del251. View

16.

Hoshino K, Takeuchi O, Kawai T, Sanjo H, Ogawa T, Takeda Y . Cutting edge: Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the Lps gene product. J Immunol. 1999; 162(7):3749-52. View

17.

Muller M, Pfannes S, Ayoub M, Hoffmann P, Bessler W, Mittenbuhler K . Immunostimulation by the synthetic lipopeptide P3CSK4: TLR4-independent activation of the ERK1/2 signal transduction pathway in macrophages. Immunology. 2001; 103(1):49-60. PMC: 1783214. DOI: 10.1046/j.1365-2567.2001.01203.x. View

18.

Isobe T, Minoura H, Tanaka K, Shibahara T, Hayashi N, Toyoda N . The effect of RANTES on human sperm chemotaxis. Hum Reprod. 2002; 17(6):1441-6. DOI: 10.1093/humrep/17.6.1441. View

19.

Shimada M, Hernandez-Gonzalez I, Gonzalez-Robanya I, Richards J . Induced expression of pattern recognition receptors in cumulus oocyte complexes: novel evidence for innate immune-like functions during ovulation. Mol Endocrinol. 2006; 20(12):3228-39. DOI: 10.1210/me.2006-0194. View

20.

Okazaki T, Abe S, Yoshida S, Shimada M . Seminal plasma damages sperm during cryopreservation, but its presence during thawing improves semen quality and conception rates in boars with poor post-thaw semen quality. Theriogenology. 2008; 71(3):491-8. DOI: 10.1016/j.theriogenology.2008.08.014. View