Abstract
Peroxiredoxins (PRDXs) are important antioxidant enzymes reported to have a role in sperm function and male fertility. However, how PRDXs affects male fertility remain fundamental unanswered questions. We therefore sought to investigate the role of these enzymes in sperm function and fertilisation. In this in vitro trial, mouse spermatozoa were incubated with different concentrations of conoidin A (1, 10, or 100 µM), a specific inhibitor of PRDXs. Our results demonstrated that inhibition of PRDXs by conoidin A significantly decreased the oxidized form of peroxiredoxins (PRDXs-SO3) in spermatozoa. Decreased PRDX activity was associated with a significant reduction in sperm motility parameters, viability, and intracellular ATP, whereas ROS levels, DNA fragmentation, and loss of mitochondrial membrane potential were increased. Simultaneously capacitation and the acrosome reaction were also significantly inhibited perhaps as a consequence of decreased tyrosine phosphorylation and protein kinase-A activity. In addition, fertilisation and early embryonic development were adversely affected following PRDXs inhibition in spermatozoa. Taken together, our data demonstrate that decreased PRDX activity directly affects male fertility due to negative effects on important functions and biochemical properties of spermatozoa, ultimately leading to poor fertilisation and embryonic development.
Highlights
Mammalian spermatozoa must undergo several functional and physiological modifications prior to fertilisation
Our western blot results showed that conoidin A did decrease PRDXs-SO3 levels in spermatozoa, with or without the addition of glucose oxidase (P < 0.001 and P = 0.001) (Fig. 1)
PRDXs are antioxidant enzymes, which are present in almost all cell types and function to maintain cell homeostasis by regulating H2O2 levels
Summary
Mammalian spermatozoa must undergo several functional and physiological modifications prior to fertilisation. Capacitation and the acrosome reaction are fundamental to sperm-oocyte fusion[1] Both events are regulated by complex interactions that involve several signalling cascades, such as intracellular calcium influx, membrane fluidity, cyclic AMP (cAMP), protein kinase-A (PKA), and tyrosine phosphorylation[2,3,4,5,6,7,8]. Ozkosem et al reported that a lack of PRDXs impairs sperm motility, capacitation, and DNA integrity[22] Another recent study demonstrated that PRDXs levels are reduced in infertile male patients[23]. We analysed levels of intracellular ATP, mitochondrial membrane potential (MMP), ROS, DNA fragmentation index (DFI), lactate dehydrogenase (LDH; as a measure of cytotoxicity), PKA activity, and tyrosine phosphorylation in order to identify the molecular mechanism underlying PRDX inhibition in spermatozoa and male infertility
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