Repositorio
Institucional

Villegas, Juana V.

Uribe, Pamela#Cabrillana, Maria E.#Fornes, Miguel W.#Treulen, Favian#Boguen, Rodrigo#Isachenko, Vladimir#Isachenkob, Evgenia#Sanchez, Raul

Nitrosative stress in human spermatozoa causes cell death characterized by induction of mitochondrial permeability transition-driven necrosis

WOLTERS KLUWER MEDKNOW PUBLICATIONS

ASIAN JOURNAL OF ANDROLOGY

en

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.

Artículo original

This work was supported by the National Fund of Science and Technology (Grant number 1130888 to RS), the University of La Frontera (Grant number DI17-0035 to JVV), the CONICYT, Chile, PAI/Fund for Insertion in the Academy, Call 2016 (Grant number PA179160030 to PU), and a scholarship from the German Academic Exchange Service, DAAD, Germany (to JVV).

Este trabajo fue apoyado por el Fondo Nacional de Ciencia y Tecnología (Número de subvención 1130888 a RS), la Universidad de La Frontera (Número de subvención DI17-0035 a JVV), CONICYT, Chile, PAI/Fondo de Inserción en la Academia, Convocatoria 2016 (Número de subvención PA179160030 a PU), y una beca del Servicio Alemán de Intercambio Académico, DAAD, Alemania (a JVV).

10.4103/aja.aja_29_18

pdf

necrosis# nitrosative stress# oxidative stress# peroxynitrite# sperm cell death

http://dx.doi.org/10.4103/aja.aja_29_18

Andrology# Urology & Nephrology

necrosis# estrés nitrosativo# estrés oxidativo# peroxinitrito# muerte de espermatozoides

Biología Reproductiva

Biología Molecular

Fisiología

WOS:000449167200013

Nitrosative stress in human spermatozoa causes cell death characterized by induction of mitochondrial permeability transition-driven necrosis

Artículo original

version publicada

WOLTERS KLUWER MEDKNOW PUBLICATIONS

ASIAN JOURNAL OF ANDROLOGY

Andrología# Urología y Nefrología

1008-682X

en

National Fund of Science and Technology 1130888#UFRO DI17-0035#ANID CONICYT PA179160030

UFRO DI17-0035

ANID CONICYT

PAI/Fund for Insertion in the Academy PA179160030

German Academic Exchange Service, DAAD, Germany

This work was supported by the National Fund of Science and Technology (Grant number 1130888 to RS), the University of La Frontera (Grant number DI17-0035 to JVV), the CONICYT, Chile, PAI/Fund for Insertion in the Academy, Call 2016 (Grant number PA179160030 to PU), and a scholarship from the German Academic Exchange Service, DAAD, Germany (to JVV).

pdf

dorada#verde

acceso abierto

acceso abierto

CC BY-NC-SA

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