Nitric Oxide Signaling in Sperm Function and Male Fertility
Summary
Nitric oxide (NO) is a gaseous signalling molecule that exerts concentration-dependent effects on spermatozoa, modulating key events from maturation to fertilisation. At physiological levels, NO is generated by constitutive and inducible nitric oxide synthase (NOS) isoforms within germ cells and supporting somatic cells of the testis. This basal production of NO activates soluble guanylyl cyclase, elevating cyclic GMP (cGMP) and triggering downstream kinases that regulate motility patterns, membrane dynamics and the acrosome reaction. During capacitation, a series of biochemical and biophysical changes primes sperm for zona pellucida penetration; NO plays an essential role in this process by fine-tuning intracellular calcium fluxes and protein phosphorylation events. Conversely, excessive NO or its reactive derivatives such as peroxynitrite can induce nitrosative stress, lipid peroxidation and DNA fragmentation, compromising sperm viability and fertilising capacity. A balanced NO milieu is therefore critical for optimal sperm function, with relevance to both natural conception and assisted reproductive technologies. Recent advances have begun to elucidate the interplay between NO and other gasotransmitters, antioxidant defences and the structural components of the sperm tail, offering novel insights into therapeutic modulation of male fertility.
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Nitric Oxide Signaling in Sperm Function and Male Fertility publication trend
The graph below shows the total number of articles in nitric oxide signaling in sperm function and male fertility across all publications each year (not limited to Nature Index journals).
Technical terms
Nitric oxide (NO): A small gaseous messenger produced by nitric oxide synthases that regulates cellular signalling via cGMP production.
Reactive nitrogen species (RNS): Derivatives of NO, including peroxynitrite, that can induce oxidative and nitrosative damage at high concentrations.
Capacitation: A sequence of physiological and biochemical changes rendering sperm capable of undergoing the acrosome reaction and fertilising an oocyte.
Acrosome reaction: Exocytosis of the acrosomal vesicle at the sperm head, enabling penetration of the egg’s protective zona pellucida.
Soluble guanylyl cyclase (sGC): An enzyme activated by NO that synthesises cyclic GMP, a second messenger in sperm signalling pathways.
References
- FeTPPS, a Peroxynitrite Decomposition Catalyst, Ameliorates Nitrosative Stress in Human Spermatozoa. Antioxidants (2023).
- The Roles of NO and H2S in Sperm Biology: Recent Advances and New Perspectives. International Journal of Molecular Sciences (2020).
- Role of reactive nitrogen species in male infertility. Reproductive Biology and Endocrinology (2012).
- The Impact of Rumen-Protected L-Arginine Oral Supplementation on Libido, Semen Quality, Reproductive Organ Biometry, and Serum Biochemical Parameters of Rams. Frontiers in Veterinary Science (2022).
- Regulation of boar sperm functionality by the nitric oxide synthase/nitric oxide system. Journal of Assisted Reproduction and Genetics (2019).
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