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Endocannabinoids Are Widely Expressed in the Human Testis

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In a paper published today in Scientific Reports, researchers present findings which indicate that the endocannabinoid system (ECS) may be directly involved in the regulation of the physiology of the human testis.1

The endocannabinoid system (ECS) is a lipid signaling system made up of ligands, enzymes and receptors, which helps the body to maintain a state of homeostasis. Endocannabinoids, endogenous cannabis-like ligands such as N-arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG), bind to G-protein-coupled receptors (CB1 and CB2) found throughout the body, where they play a role in a variety of behavioral, neuroendocrine and autonomic functions. Disruption to this system has been linked to disorders ranging from diabetes to infertility.

The role of the ECS in the reproductive system is widely recognized and a number of studies have pointed to its potential involvement in the preservation of normal sperm function and therefore male fertility.2

A group of researchers led by Rigshospitalet’s Professor Niels E. Skakkebaek set out to build on this knowledge by investigating the presence of ECS components in human testis tissue. Using tissue samples from 15 patients with testicular germ cancer, they found the presence of the endocannabinoid 2-AG, endocannabinoid receptors, and enzymes FAAH and ABHD2 at various stages of germ cell development. Interestingly, these ECS components displayed a distinct pattern across different stages of maturation, suggesting that the ECS may play a role in regulating sperm cell development.

“I was surprised to find that endocannabinoids were so widely expressed in all cell types in the testis, both in the germ cells and the hormone-producing cells. Andrologists like me have for generations been focusing on other hormone aspects, but overlooked the possibility that endocannabinoids may participate in the normal sperm and hormone production”, says Professor Skakkebaek, adding, “We did see a hint a couple of years ago, when we found that young Danish men, who had used marijuana, had significantly poorer sperm counts than their peers.”

Since endocannabinoid receptors can also bind active agents in cannabis, the findings open up questions about the ways that cannabis use may interfere with human testis function and sperm development. Further research will be needed to address these possible impacts.


1- https://www.nature.com/articles/s41598-019-49177-y 
2- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4420685/