Infliximab may reverse the toxic effects induced by tumor necrosis factor alpha in human spermatozoa: an in vitro model

Tamer M. Said, Agarwal A, Ashok Agarwal, Tommaso Falcone, Falcone T, Rakesh K Sharma, Rakesh Sharma, Mohamed A. Bedaiwy, Li L, Liang Li
Fertility and sterility · 2005 · vol. 83(6) , pp. 1665–1673 · doi:10.1016/j.fertnstert.2004.11.068 · PMID:15950634 · W2107994883
article OA: closed CC0 ⤵ 21 in-corpus citations
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This study used an in vitro model to investigate if infliximab could reverse the toxic effects of tumor necrosis factor alpha on human spermatozoa.

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Abstract

ObjectiveTo examine the toxic effects of tumor necrosis factor alpha (TNF-alpha) on ejaculated spermatozoa and evaluate the ability of infliximab to reverse these effects.DesignProspective controlled study.SettingCleveland Clinic Foundation, Cleveland, Ohio.Patient(s)Thirty-one healthy sperm donors.Intervention(s)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).Main outcome measure(s)Sperm motility, functional integrity of plasma membrane, and DNA fragmentation.Result(s)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.Conclusion(s)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.

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MeSH descriptors

Antibodies, Monoclonal Tumor Necrosis Factor-alpha Tumor Necrosis Factor-alpha Analysis of Variance Antibodies, Monoclonal DNA Fragmentation DNA Fragmentation Dose-Response Relationship, Immunologic Humans Infliximab Male Prospective Studies Spermatozoa Spermatozoa Sperm Motility Sperm Motility Time Factors Tumor Necrosis Factor-alpha

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