Cannabinoid receptor activates spermatozoa
During fertilization, a sperm must first fuse with the plasma membrane and then penetrate the female egg in order to penetrate it. To this end, sperm cells go through a process known as the acrosome reaction which is the reaction that occurs in the acrosome of the sperm as it approaches the egg. In the lab, this so-called acrosome reaction is considered a test for analysing the ability of semen to accomplish fertilisation. A receptor for an endogenous cannabinoid plays a crucial role in this process. A team of biologists from Bochum and Bonn, headed by Prof Dr Dr Dr Hanns Hatt, have been the first one to provide a proof of the so-called G protein-coupled receptors 18 (GPR18) in spermatozoa, following a comprehensive analysis. They published their findings in Scientific Reports.
Researchers find 223 additional receptors
Specialised in olfaction research, the team from Bochum had detected as many as 60 olfactory receptors in spermatozoa early this year, and has activated and localised ten of them. “In the current study, we have focused on the remaining G protein-coupled receptors, which, rather than being olfactory receptors, bind other substances,” explains Hanns Hatt. Analysing samples by numerous donors, the researchers investigated which genes are expressed in spermatozoa; their conclusion was that the number of receptors totalled 223. The three most common ones include receptor GPR18, a cannabinoid receptor that has recently been described for the first time.
New receptor is more sensitive to NAGly than classical ones
“The receptor reacts to the herbal cannabis agent THC as well as to the endogenous fatty acid NAGly, which is associated with the cannabinoid system,” says Hatt. “It is much more sensitive to NAGly than the classical, long-known cannabinoid receptors.” Activating the receptor, which is situated in the centre of spermatozoa, can trigger the so-called acrosome reaction. In the course of this process, the spermatozoon’s surface is altered as it approaches the egg. Without this reaction, the spermatozoon cannot penetrate the egg cell.
Cannabinoids in female reproductive tract
Scientists know that endocannabinoids occur in both the male and the female genital tract. Studies suggest that in women their concentration increases during the fertile days. “The endocannabinoid activates the spermatozoa for fertilization” concludes Hanns Hatt. The GPR18 receptor also occurs in other tissues in the human body, for example in the brain and in the heart. However, its function was not known until now.
The studies were funded by the National Science Centre Poland (project DEC. 2013/11/8/N27/04865), the collaborative Research Centre 642 at the German Research Foundation, and the Heinrich und Alma Vogelsang-Stiftung.
Caroline Flegel at al.: Characterization of non-olfactory GPCRs in human sperm with a focus on GPR18, in: Scientific Reports, 2016, DOI: 10.1038/srep32255