New insights into sperm physiology regulation: Enlightenment from G-protein-coupled receptors

G-protein-coupled receptors are critical in many physiological and pathological processes in various organs. Serving as the control panel for sensing extracellular stimuli, G-protein-coupled receptors recognise various ligands, including light, temperature, odours, pheromones, hormones, neurotransmitters, chemokines, etc. Most recently, G-protein-coupled receptors residing in spermatozoa have been found to be indispensable for sperm function.

Here, we have summarised cutting-edge findings on the functional mechanisms of G-protein-coupled receptors that are known to be associated with sperm functions and the activation of their downstream effectors, providing new insights into the roles of G-protein-coupled receptors in sperm physiology.

Emerging studies hint that alterations in G-protein-coupled receptors could affect sperm function, implicating their role in fertility, but solid evidence needs to be continuing excavated with various means. Several members of the G-protein-coupled receptor superfamily, including olfactory receptors, opsins, orphan G-protein-coupled receptors, CXC chemokine receptor 4, CC chemokine receptor 5 and CC chemokine receptor 6 as well as their downstream effector β-arrestins, etc., were suggested to be essential for sperm motility, capacitation, thermotaxis, chemotaxis, Ca²⁺ influx through CatSper channel and fertilisation capacity.

The present review provides a comprehensive overview of studies describing G-protein-coupled receptors and their potential action in sperm function. We also present a critical discussion of these issues, and a possible framework for future investigations on the diverse ligands, biological functions and cell signalling of G-protein-coupled receptors in spermatozoa. Here, the G-protein-coupled receptors and their related G proteins that specifically were identified in spermatozoa were summarised, and provided references valuable for further illumination, despite the evidence that is not overwhelming in most cases.