Bliss* blocks sperm. Evidence suggests that human male fertility is impacted by long-term exposure to marijuana. Indeed, endocannabinoids and their receptors are present in the male reproductive tract, further suggesting a functional role in fertility, but there has been no genetic test to clarify mechanisms. Now, in a paper on p. 235 of this issue, Sun et al. characterize the phenotype of mice genetically lacking FAAH, fatty acid amide hydrolase. Male mice homozygous for the Faah knockout have elevated levels of anandamide, an endocannabinoid, in the reproductive system, and their sperm have decreased ability to fertilize due to poor penetration of the egg's zona pellucida. These results point to previously unsuspected pathways regulating sperm function. But perhaps more importantly, they are of great clinical significance: because sperm of chronic marijuana users, as well as sperm in Faah-mutant males are exposed to enhanced cannabinoid/endocannbinoid signaling, clinically beneficial effects of anandamide must be weighed against potentially harmful effects on fertility. (*Note: The term anandamide for the endocannabinoid arachidonoylethanolamide was coined by the discoverer of this compound, Dr. Mechoulam; "ananda" means bliss or ecstasy.)
Xiaofei Sun, Haibin Wang, Masaru Okabe, Kenneth Mackie, Philip J. Kingsley, Lawrence Marnett, Benjamin Cravatt, and Sudhansu K. Dey. Genetic Loss of Faah Compromises Male Fertility in Mice. Biol Reprod 2009; 235-242. Published in BOR-Papers in Press 5 November 2008; DOI: 10.1095/biolreprod.108.072736
Offspring of male geezers: a new wrinkle. Although mammalian males can reproduce until late in life, evidence of hazards to offspring has emerged in human and animal models. Two papers in this issue (pp. 337 and 343) provide clear, well-controlled data of deleterious effects on the offspring of aged male mice mated to females of prime reproductive age. The offspring from the elderly males exhibit abnormalities not only in several behavioral traits, but also in reproductive fitness and longevity. The early death of offspring sired by old mice was heralded by rapid weight loss. Moreover, mating the offspring derived from aged males resulted in the production of pups exhibiting decreased weights at weaning when compared with pups from the offspring of younger males: an apparent transgenerational effect. The defects causing the abnormalities in offspring are unknown and should be the objective of intriguing studies in the future.
Silvia García-Palomares, José F. Pertusa, José Mi ñarro, Miguel A. García-Pérez, Carlos Hermenegildo, Francisco Rausell, Antonio Cano, and Juan J. Tarín. Long-Term Effects of Delayed Fatherhood in Mice on Postnatal Development and Behavioral Traits of Offspring. Biol Reprod 2009; 337-342. Published in BOR-Papers in Press 15 October 2008; DOI: 10.1095/biolreprod.108.072066
Silvia García-Palomares, Samuel Navarro, José F. Pertusa, Carlos Hermenegildo, Miguel A. García-Pérez, Francisco Rausell, Antonio Cano, and Juan J. Tarín. Delayed Fatherhood in Mice Decreases Reproductive Fitness and Longevity of Offspring. Biol Reprod 2009; 343-349. Published in BOR-Papers in Press 15 October 2008; DOI: 10.1095/biolreprod.108.073395