title: The effects in vitro of TNF-α and its antagonist 'etanercept' on ejaculated human sperm.
abstract: Tumour necrosis factor (TNF)-α is primarily involved in the regulation of cell proliferation and apoptosis; in addition it possesses pro-inflammatory properties. Anti-TNF-α strategies involve either administration of anti-TNF-α antibody or soluble TNF receptor to mop up circulating TNF-α. Etanercept, a recombinant human TNF-α receptor, was found to be effective in the treatment of rheumatoid arthritis. The impact of TNF-α inhibitors on human fertility is of notable interest. This in vitro study investigated the effect of different concentrations of TNF-α and etanercept used alone or in combination on sperm viability, motility, mitochondrial function, percentage of apoptosis and chromatin integrity in swim-up selected human spermatozoa. A negative effect of TNF-α (300 and 500ng mL-1) and etanercept (from 800µg mL-1to 2000µg mL-1) individually on sperm viability, motility, mitochondrial function, percentage of apoptotic spermatozoa and sperm DNA integrity was demonstrated. However, at concentrations of 100 and 200µg mL-1, etanercept can block, in a significant way, the toxic effects of TNF-α (500ng mL-1) on studied sperm characteristics. Our results confirm that TNF-α has a detrimental effect on sperm function and suggest, for the first time, that etanercept may counteract the in vitro toxic action of TNF-α. This data appears to be quite promising, although further studies, both in vivo and in vitro, are needed to understand the exact mechanism of action of TNF-α and TNF-α antagonists on sperm function.
authors.affiliation: Rheumatology Unit, Azienda Ospedaliera Universitaria Senese, Policlinico Le Scotte, Viale Bracci, 14, 53100, Siena, Italy.
authors.forename: Nicola A
authors.initials: NA
authors.lastname: Pascarelli
authors.affiliation: Rheumatology Unit, Azienda Ospedaliera Universitaria Senese, Policlinico Le Scotte, Viale Bracci, 14, 53100, Siena, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Fioravanti
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena, Policlinico Le Scotte, Viale Bracci, 14, 53100, Siena, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Moretti
authors.affiliation: Rheumatology Unit, Azienda Ospedaliera Universitaria Senese, Policlinico Le Scotte, Viale Bracci, 14, 53100, Siena, Italy.
authors.forename: Giacomo M
authors.initials: GM
authors.lastname: Guidelli
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena, Policlinico Le Scotte, Viale Bracci, 14, 53100, Siena, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Mazzi
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena, Policlinico Le Scotte, Viale Bracci, 14, 53100, Siena, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Collodel
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002843:Chromatin / Q000737:chemistry / Q000187:drug effects / Q000276:immunology; D053938:DNA Fragmentation / Q000187:drug effects; D000068800:Etanercept / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D010718:Phosphatidylserines / Q000378:metabolism; D011994:Recombinant Proteins / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology; D013081:Sperm Motility / Q000187:drug effects; D013094:Spermatozoa / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D013499:Surface Properties / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000009:adverse effects / Q000037:antagonists & inhibitors* / Q000235:genetics; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002843:Chromatin; D010718:Phosphatidylserines; D011994:Recombinant Proteins; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept