Synthetic cannabinoid improves binding with zona pellucida of the egg


Even though smoking cessation is the best solution for male and female smokers who have borderline fertility, in vitro use of synthetic cannabinoid analogs may offer an alternative in patients who cannot or will not stop smoking.

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Studies have shown that sperm carry a nicotinic acetylcholine receptor and respond to nicotine from tobacco. Sperm also have cannabinoid (CB) receptors and respond to marijuana and endocannabinoids or synthetic CB chemicals. 


Researchers at the University of Buffalo previously reported that sperm from two thirds of tobacco smokers showed a significant drop in fertilizing capacity, including a reduced binding to the zona pellucida of the egg. The new study, by these researchers working in collaboration with others at NortheasternUniversity in Boston, studied the effects of a CB agonist (AM-1346, an analog of the endocannabinoid anandamide). The investigators studied the sperm from chronic tobacco smokers in 22 in vitro hemizona assay (HZA) tests.


“This is a very potent, special chemical, and we are studying a number of others like it,” said lead investigator Lani Burkman, PhD, associate professor of gynecology at the University of Buffalo.


The eight selected test subjects, all chronic tobacco smokers, previously had been tested against normal controls using an assay that incubates their sperm with halves of a non-living, donated human zona pellucida, Dr. Burkman said. Four of the eight subjects had normal sperm function (group I) and four showed reduced fertilizing function (group II). The HZA tests were repeated using the new drug. The researchers compared two groups of sperm from each smoker: sperm washed in standard medium (no drug) versus sperm that were washed in medium containing the CB agonist.


After exposing the sperm to AM-1346 at any concentration, the response in Group II depended on the quality of their semen sample. When the semen sample had poor quality (low count and low motility), all of the experiments showed, on average, a doubling of zona pellucida sperm binding compared with un-treated sperm. For the men in Group II who showed good semen quality, none of the tests showed stimulation due to the drug.


The sperm in group I behaved differently in the presence of the drug. Only one of nine tests showed zona pellucida binding enhancement, while eight of the tests revealed an inhibition of egg binding.


These experiments also tested a low concentration of AM-1346 (one HZA) compared with a higher concentration of the drug (second HZA) in men from both groups. In six of seven experiments, the higher dose of AM-1346 produced a better HZA score. The researchers concluded that most smoking men show a stimulation of egg binding if the dose of AM-1346 is high enough.

“All male and female patients should be counseled to quit smoking,” Dr. Burkman told Renal & Urology News. “Every organ system is ravaged by tobacco use, not just the reproductive area. And it’s not just the smoke. According to our research, nicotine itself is directly changing reproductive function. So, men who are turning to the nicotine patch or gum are still doing damage to their sperm.”