Universität zu Köln

Uribe, Pamela, Cabrillana, Maria E., Fornes, Miguel W., Treulen, Favian, Boguen, Rodrigo ORCID: 0000-0002-0325-743X, Isachenko, Vladimir, Isachenkob, Evgenia, Sanchez, Raul and Villegas, Juana V. (2018). Nitrosative stress in human spermatozoa causes cell death characterized by induction of mitochondrial permeability transition-driven necrosis. Asian J. Androl., 20 (6). S. 600 - 608. MUMBAI: WOLTERS KLUWER MEDKNOW PUBLICATIONS. ISSN 1745-7262

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Abstract

Peroxynitrite is a highly reactive nitrogen species and a potent inducer of apoptosis and necrosis in somatic cells. Peroxynitrite-induced nitrosative stress has emerged as a major cause of impaired sperm function; however, its ability to trigger cell death has not been described in human spermatozoa. The objective here was to characterize biochemical and morphological features of cell death induced by peroxynitrite-mediated nitrosative stress in human spermatozoa. For this, spermatozoa were incubated with and without (untreated control) 3-morpholinosydnonimine (SIN-1), in order to generate peroxynitrite. Sperm viability, mitochondrial permeability transition (MPT), externalization of phosphatidylserine, DNA oxidation and fragmentation, caspase activation, tyrosine nitration, and sperm ultrastructure were analyzed. The results showed that at 24 h of incubation with SIN-1, the sperm viability was significantly reduced compared to untreated control (P<0.001). Furthermore, the MPT was induced (P<0.01) and increment in DNA oxidation (P<0.01), DNA fragmentation (P<0.01), tyrosine nitration (P<0.0001) and ultrastructural damage were observed when compared to untreated control. Caspase activation was not evidenced, and although phosphatidylserine externalization increased compared to untreated control (P<0.001), this process was observed in <10% of the cells and the gradual loss of viability was not characterized by an important increase in this parameter. In conclusion, peroxynitrite-mediated nitrosative stress induces the regulated variant of cell death known as MPT-driven necrosis in human spermatozoa. This study provides a new insight into the pathophysiology of nitrosative stress in human spermatozoa and opens up a new focus for developing specific therapeutic strategies to better preserve sperm viability or to avoid cell death.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Uribe, Pamela UNSPECIFIED UNSPECIFIED UNSPECIFIED Cabrillana, Maria E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Fornes, Miguel W. UNSPECIFIED UNSPECIFIED UNSPECIFIED Treulen, Favian UNSPECIFIED UNSPECIFIED UNSPECIFIED Boguen, Rodrigo UNSPECIFIED orcid.org/0000-0002-0325-743X UNSPECIFIED Isachenko, Vladimir UNSPECIFIED UNSPECIFIED UNSPECIFIED Isachenkob, Evgenia UNSPECIFIED UNSPECIFIED UNSPECIFIED Sanchez, Raul UNSPECIFIED UNSPECIFIED UNSPECIFIED Villegas, Juana V. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-167987
DOI:	10.4103/aja.aja_29_18
Journal or Publication Title:	Asian J. Androl.
Volume:	20
Number:	6
Page Range:	S. 600 - 608
Date:	2018
Publisher:	WOLTERS KLUWER MEDKNOW PUBLICATIONS
Place of Publication:	MUMBAI
ISSN:	1745-7262
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language NITRIC-OXIDE SYNTHASE; DNA-DAMAGE; PHOSPHATIDYLSERINE EXPOSURE; OXIDATIVE STRESS; HUMAN SPERM; PROTEIN MODIFICATIONS; PEROXYNITRITE; MOTILITY; FRAGMENTATION; LOCALIZATION Multiple languages Andrology; Urology & Nephrology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/16798