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 500 ng mL-1) and etanercept (from 800 µg mL-1 to 2000 µg 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 200 µg mL-1, etanercept can block, in a significant way, the toxic effects of TNF-α (500 ng 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.

Pascarelli, N.A., Fioravanti, A., Moretti, E., Guidelli, G.M., Mazzi, L., Collodel, G. (2017). The effects in vitro of TNF-α and its antagonist ‘etanercept’ on ejaculated human sperm. REPRODUCTION FERTILITY AND DEVELOPMENT, 29(6), 1169-1177 [10.1071/RD16090].

The effects in vitro of TNF-α and its antagonist ‘etanercept’ on ejaculated human sperm

PASCARELLI, NICOLA ANTONIO;FIORAVANTI, ANTONELLA;MORETTI, ELENA;GUIDELLI, GIACOMO MARIA;MAZZI, LUCIA;COLLODEL, GIULIA
2017-01-01

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 500 ng mL-1) and etanercept (from 800 µg mL-1 to 2000 µg 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 200 µg mL-1, etanercept can block, in a significant way, the toxic effects of TNF-α (500 ng 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.
2017
Pascarelli, N.A., Fioravanti, A., Moretti, E., Guidelli, G.M., Mazzi, L., Collodel, G. (2017). The effects in vitro of TNF-α and its antagonist ‘etanercept’ on ejaculated human sperm. REPRODUCTION FERTILITY AND DEVELOPMENT, 29(6), 1169-1177 [10.1071/RD16090].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/1006587