Downregulation of DJ-1 Fails to Protect Mitochondrial Complex I Subunit NDUFS3 in the Testes and Contributes to the Asthenozoospermia

Abstract

Asthenozoospermia (AS), an important cause of male infertility, is characterized by reduced sperm motility. Among the aetiologies of AS, inflammation seems to be the main cause. DJ-1, a conserved protein product of the PARK7 gene, is associated with male infertility and plays a role in oxidative stress and inflammation. Although our previous studies showed that a reduction in DJ-1 was accompanied by mitochondrial dysfunction in the sperm of patients with AS, the specific mechanism underlying this association remained unclear. In this study, we found that compared to the patients without AS, the expression of mitochondrial protein nicotinamide adenine dinucleotide dehydrogenase (ubiquinone) Fe-S protein 3 (NDUFS3) was also significantly decreased in the sperm of patients with AS. Similarly, decreased expression of DJ-1 and NDUFS3 and reduced mitochondria complex I activity were evident in a rat model of AS. Moreover, we showed that the interaction between DJ-1 and NDUFS3 in rat testes was weakened by ORN treatment. These results suggest that the impaired mitochondrial activity could be due to the broken interaction between DJ-1 and NDUFS3 and that downregulation of DJ-1 in sperm and testes contributes to AS pathogenesis.

Cryopreservation Differentially Alters the Proteome of Epididymal and Ejaculated Pig Spermatozoa

“…Three of them, Ndufs2, Uqcr10, and Cox2, are key mitochondrial electron transport complex proteins specifically involved in complexes I, III, and IV, respectively [45]. DJ-1—a protein deglycase—contributes in the regulation of mitochondrial complex I and it would be involved in the control of oxidative stress [46,47]. Finally, Ogdh is an enzyme of the Krebs cycle that would also be involved in mitochondrial functionality, specifically in ROS generation [48].…”

Natrium Benzoate Alleviates Neuronal Apoptosis via the DJ-1-Related Anti-oxidative Stress Pathway Involving Akt Phosphorylation in a Rat Model of Traumatic Spinal Cord Injury

“…The DJ-1 gene belongs to the Thi/PfpI superfamily (Wang et al, 2018), which is located at chromosome 1p36 and encodes a ubiquitous protein consisting of 189 amino acids (Van Duijn et al, 2001). Among its biological functions, the most important is protecting against oxidative stress (Kahle et al, 2009).…”

Sperm morphometry is affected by increased inbreeding in the Retinta cattle breed: A molecular approach

“…Our functional analysis revealed four candidate genes highly influenced by the increase of inbreeding. The two most affected genes ( PARK7 and VAMP3 , BTA16, p < 0.0001) have been previously associated with spermatogenesis and sperm maturation in mice models (Sun et al, 2014; Y. Wang et al, 2018) and chicken (Zhang et al, 2017). From these, PARK7 was more associated with mitochondrial function than sperm head shape in rats and human beings (Sun et al, 2014; Y. Wang et al, 2018), suggesting that its role in the reproductive process would be more related to sperm motility than morphometry.…”

“…The two most affected genes ( PARK7 and VAMP3 , BTA16, p < 0.0001) have been previously associated with spermatogenesis and sperm maturation in mice models (Sun et al, 2014; Y. Wang et al, 2018) and chicken (Zhang et al, 2017). From these, PARK7 was more associated with mitochondrial function than sperm head shape in rats and human beings (Sun et al, 2014; Y. Wang et al, 2018), suggesting that its role in the reproductive process would be more related to sperm motility than morphometry. In the case of VAMP3 , it encodes a protein with a key function during acrosome formation and capacitation through the development of ternary trans‐SNARE complexes which it was found that modulate the sperm shape in a porcine model (Tsai et al, 2010).…”