Summary: Receptor reacts to THC, as well as NAGly, a new study reports.
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 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.
Funding: The research was funded by the National Science Centre Poland, German Research Foundation, Heinrich und Alma Vogelsang-Stiftung.
Source: Meike Drießen – RUB
Image Source: This NeuroscienceNews.com image is credited to the researchers/Scientific Reports.
Original Research: Full open access research for “Characterization of non-olfactory GPCRs in human sperm with a focus on GPR18” by Caroline Flegel, Felix Vogel, Adrian Hofreuter, Sebastian Wojcik, Clara Schoeder, Katarzyna Kieć-Kononowicz, Norbert H. Brockmeyer, Christa E. Müller, Christian Becker, Janine Altmüller, Hanns Hatt and Günter Gisselmann in Scientific Reports. Published online August 30 2016 doi:10.1038/srep32255
Characterization of non-olfactory GPCRs in human sperm with a focus on GPR18
G protein-coupled receptors (GPCRs) transduce external chemical cues into intracellular signals and are involved in a plethora of physiological processes, but knowledge regarding the function of these receptors in spermatozoa is limited. In the present study, we performed RNA-Seq and analyzed the expression of the all GPCRs except olfactory receptors in human spermatozoa. We revealed the expression of up to 223 different GPCR transcripts in human spermatozoa (FPKM > 0.1) and identified GPR18, a newly described cannabinoid receptor, together with GPR137 and GPR135, as one of the three most highly expressed GPCRs. To date, the expression of GPR18 was completely unknown in human spermatozoa. We confirmed GPR18 expression using RT-PCR and immuncytochemistry experiments and localized the GPR18 protein in the midpiece of human spermatozoa. Stimulation of human spermatozoa with the GPR18 ligand N-arachidonoylglycine induced the phosphorylation of 12 protein kinases, some of them are for example known to be involved in the acrosome reaction. In line with this, N-arachidonoylglycine affected the cytoskeleton by changing levels of F-actin and inducing the acrosome reaction in human spermatozoa in a concentration-dependent manner. Our results indicate that GPR18 might be involved in physiological processes of human spermatozoa, suggesting GPR18 to be a potential player in sperm physiology.
“Characterization of non-olfactory GPCRs in human sperm with a focus on GPR18” by Caroline Flegel, Felix Vogel, Adrian Hofreuter, Sebastian Wojcik, Clara Schoeder, Katarzyna Kieć-Kononowicz, Norbert H. Brockmeyer, Christa E. Müller, Christian Becker, Janine Altmüller, Hanns Hatt and Günter Gisselmann in Scientific Reports. Published online August 30 2016 doi:10.1038/srep32255