Infliximab may reverse the toxic effects induced by tumor necrosis factor alpha in human spermatozoa: an in vitro model.
OBJECTIVE
To examine the toxic effects of tumor necrosis factor alpha (TNF-alpha) on ejaculated spermatozoa and evaluate the ability of infliximab to reverse these effects.


METHODS
Prospective controlled study.


METHODS
Cleveland Clinic Foundation, Cleveland, Ohio.


METHODS
Thirty-one healthy sperm donors.


METHODS
Exposure of human spermatozoa to varying concentrations of TNF-alpha (100, 300, 400, 500 pg/mL, and 2.5 microg/mL) and infliximab (400 microg/mL).


METHODS
Sperm motility, functional integrity of plasma membrane, and DNA fragmentation.


RESULTS
Spermatozoa quality declined following incubation with TNF-alpha in a dose-dependent and time-dependent manner. Sperm motility and membrane integrity were higher in the samples incubated with TNF-alpha plus infliximab than in the samples treated with TNF-alpha only. These parameters improved significantly and were comparable with both controls and sperm incubated with infliximab alone. Similarly, the percentage of spermatozoa with DNA fragmentation improved significantly following incubation with TNF-alpha plus infliximab and again was comparable with both controls and sperm incubated with infliximab alone.


CONCLUSIONS
Spermatozoa may be exposed to abnormal levels of TNF-alpha in the male reproductive tract or during their passage into the female reproductive tract (in cases of endometriosis). Exposing spermatozoa to pathological concentrations of TNF-alpha can result in significant loss of their functional and genomic integrity. Infliximab could potentially be used to help treat female infertility caused by endometriosis in those with elevated levels of TNF-alpha in their peritoneal fluid.
Said
Tamer M
TM
Center for Advanced Research in Human Reproduction, Infertility, and Sexual Function, The Cleveland Clinic Foundation, Cleveland, Ohio, USA.
Agarwal
Ashok
A
Falcone
Tommaso
T
Sharma
Rakesh K
RK
Bedaiwy
Mohamed A
MA
Li
Liang
L
D000704:Analysis of Variance; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D053938:DNA Fragmentation / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D000069285:Infliximab; D008297:Male; D011446:Prospective Studies; D013081:Sperm Motility / Q000276:immunology; D013094:Spermatozoa / Q000276:immunology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000633:toxicity*
D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab