©Dr. Ronen Shemesh

Endocannabinoid Signaling in Reproduction and Fertility

The International Medical Cannabis Conference

11-13 September, 2016 Dan Panorama Hotel, Tel Aviv, Israel

Localization of endocannabinoid system (ECS) elements in the human sperm cell.

Cinzia Rapino, et al. Human Reproduction Update, Vol.20, No.4 pp. 501–516, 2014

Subcellular localization of CB1-R in human ejaculated spermatozoa

Region of the head

Regions of the neck and mid-piece

Aquila Saveria , et al. THE ANATOMICAL RECORD 293:298–309 (2010)

Subcellular localization of CB1-R in human ejaculated spermatozoa

control sections incubated without the primary Ab (b,c,f)

Transverse section of the mid-piece (d-e)

Aquila Saveria , et al. THE ANATOMICAL RECORD 293:298–309 (2010)

Sagital section of the mid-piece and the tail (a)

Δ9‐Tetrahydrocannabinol (Δ9‐THC) attenuates mouse sperm motility and male fecundity

British Journal of PharmacologyVolume 165, Issue 8, pages 2575-2583, 23 MAR 2012 DOI: 10.1111/j.1476-5381.2011.01506.xhttp://onlinelibrary.wiley.com/doi/10.1111/j.1476-5381.2011.01506.x/full#f2

Basal and bicarbonate-stimulated motility is inhibited by Δ9-THC. (A) Treatment with 1 µM Δ9-THC or 10 µM Δ9-THC for 15 min progressively reduced the percentage of motile sperm. (n= 111–138 cells). At least eight cells were examined from each animal in two to three independent experiments. #P < 0.05 (untreated vs. 1 µM THC), *P < 0.05 (untreated vs. 10 µM THC).

Effect of Meth-AEA and THC on sperm motility.

A.A. Amoako, et al. Human Reproduction, Vol.28, No.8 pp. 2058–2066, 2013

Motile fractions of human spermatozoa isolated by direct swim-up were incubated with Meth-AEA (1 mM) or without (0.2% DMSO in BWW medium) for up to 90 min (A).

Removal of Meth-AEA reverses the inhibitory effect on sperm motility (B).

Effect of MET-F-AEA on sperm viability, Acrosin activity and .

Aquila Saveria , et al. THE ANATOMICAL RECORD 293:298–309 (2010)

Effects of meth-AEA on human sperm motility and viability.

A.A. Amoako, et al. Human Reproduction, Vol.28, No.8 pp. 2058–2066, 2013

AM251 reverses the AEA effect on Motility and Viability

CB1 receptor blockade by rimonabant influences sperm parameters

Aquila Saveria , et al. British Journal of Pharmacology (2010), 159, 831–841

Rimonabant positively affects sperm motility and viability. Rimonabant positively affects sperm Acrosin activity.

Rim = RimonabantURB = FAAH inhibitor URB597

LIF and AEA levels are essential for successful pregnancy.

Cinzia Rapino, et al. Human Reproduction Update, Vol.20, No.4 pp. 501–516, 2014

THC and control of hormonal cycle

Brents LK. Yale J Biol Med. 2016 Jun; 89(2): 175–191.

Cannabinoids in Blastocyst migration and implantation

Brents LK. Yale J Biol Med. 2016 Jun; 89(2): 175–191.

implantation can only occur in areas that express low CB1R and AEA.

Adequate levels of CB1R expression are required in the Fallopian tube to allow passage of the embryo into the uterus and prevent ectopic implantation.

Exposure to high concentrations of Δ9-THC or anandamide will arrest the development of the blastocyst

Cannabinoid signaling impacts various pregnancy events.

Life Sci. 2014 Feb 27; 97(1): 72–77.

AEA levels through the menstrual cycle and gestation.

Cinzia Rapino, et al. Human Reproduction Update, Vol.20, No.4 pp. 501–516, 2014

pre-eclampsia patients

ectopic or non-viable pregnancies