title: Treatment with tetrahydrocannabinol (THC) prevents infertility in male cystic fibrosis mice.
abstract: BACKGROUND
  Cystic fibrosis (CF) is a hereditary disease caused by mutations of the gene encoding a channel protein CFTR, conducting Cl- and HCO3 - ions. The disease is characterized by disturbances in most physiological systems, and more than 95% of men are infertile. The mechanism underlying the etiology of CF is associated with an imbalance of fatty acids. It has been suggested that the function of the endocannabinoid system is also disturbed in CF, because endocannabinoids are derivatives of fatty acids. We assumed, therefore, that endocannabinoid activity, which plays an important role in fertility, is disrupted in CF and could be one of the causes of infertility. The aim of the present study was to test the hypothesis that stimulation of endocannabinoid receptors in infancy would normalize their function and prevent infertility in adulthood.
  
  
  METHODS
  Knockout male mice (cftr-/-) were treated with tetrahydrocannabinol (THC), endocannabinoid receptors agonist, in infancy from days 7 until 28, daily.
  
  
  RESULTS
  CF males treated with THC were fully fertile, producing offspring comparable by the number of litters and the number of pups with wild-type mice. CF males that were not treated with THC were completely infertile.
  
  
  CONCLUSIONS
  The present study shows that (i) endocannabinoid function is impaired in CF mice, as evidenced by the regenerating effect of its stimulation on the fertility of otherwise infertile males, (ii) endocannabinoid system dysfunction is apparently the determining factor causing infertility in CF, and (iii) mild stimulation of the endocannabinoid system in infancy and adolescence appears to normalize many reproductive processes and thereby prevent infertility in CF males.
authors.affiliation: Department of Behavioral Sciences, Ariel University Center of Samaria, Ariel, Israel. tatiana@ariel.ac.il
authors.forename: Tatiana
authors.initials: T
authors.lastname: Bregman
authors.forename: Ester
authors.initials: E
authors.lastname: Fride
mesh_terms: D000818:Animals; D001724:Birth Weight; D063386:Cannabinoid Receptor Agonists; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism; D003550:Cystic Fibrosis / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D013759:Dronabinol / Q000494:pharmacology*; D005260:Female; D005298:Fertility / Q000187:drug effects*; D005303:Fertility Agents, Male / Q000494:pharmacology*; D007248:Infertility, Male / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D008098:Litter Size; D008297:Male; D051379:Mice; D018181:Mice, Inbred CFTR; D011247:Pregnancy; D043882:Receptors, Cannabinoid / Q000378:metabolism
chemical_list: D063386:Cannabinoid Receptor Agonists; D063385:Cannabinoid Receptor Modulators; D005303:Fertility Agents, Male; D043882:Receptors, Cannabinoid; D013759:Dronabinol