Philip Kingsley
Last active: 3/12/2020

Genetic loss of Faah compromises male fertility in mice.

Sun X, Wang H, Okabe M, Mackie K, Kingsley PJ, Marnett LJ, Cravatt BF, Dey SK
Biol Reprod. 2009 80 (2): 235-42

PMID: 18987328 · PMCID: PMC2804815 · DOI:10.1095/biolreprod.108.072736

Marijuana is the most commonly used illicit drug. Although there is some indication that reproductive functions in males are impaired in chronic marijuana users, the genetic evidence and underlying causes remain largely unknown. Herein we show that genetic loss of Faah, which encodes fatty acid amide hydrolase (FAAH), results in elevated levels of anandamide, an endocannabinoid, in the male reproductive system, leading to compromised fertilizing capacity of sperm. This defect is rescued by superimposing deletion of cannabinoid receptor 1 (Cnr1). Retention of Faah(-/-) sperm on the egg zona pellucida provides evidence that the capacity of sperm to penetrate the zona barrier is hampered by elevated anandamide levels. Collectively, the results show that aberrant endocannabinoid signaling via CNR1 impairs normal sperm function. Besides unveiling a new regulatory mechanism of sperm function, this study has clinical significance in male fertility.

MeSH Terms (19)

Amidohydrolases Animals Arachidonic Acids Cannabinoid Receptor Modulators Endocannabinoids Gene Deletion Genetic Complementation Test Infertility, Male Male Mice Mice, Inbred C57BL Mice, Knockout Mutagenesis, Site-Directed Polyunsaturated Alkamides Receptor, Cannabinoid, CB1 Signal Transduction Spermatozoa Sperm Motility Urogenital System

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