Jekyll and Hyde: Two Faces of Cannabinoid Signaling in Male and Female Fertility
Haibin Wang,
Sudhansu K. Dey and
Mauro Maccarrone
Departments of Pediatrics, Cell and Developmental Biology, and Pharmacology (H.W., S.K.D.), Division of Reproductive and Developmental Biology, Vanderbilt University Medical Center, Nashville, Tennessee 37232; Department of Biomedical Sciences (M.M.), University of Teramo, Teramo 64100, Italy; and Mondino-Tor Vergata Neuropharmacology Center (M.M.), University of Rome Tor Vergata, 00133 Rome, Italy
Correspondence: Address all correspondence and requests for reprints to: S. K. Dey, Division of Reproductive and Developmental Biology, Departments of Pediatrics and Cell & Developmental Biology and Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee 37232. E-mail: sk.dey{at}vanderbilt.edu; or M. Maccarrone, Department of Biomedical Sciences, University of Teramo, 64100 Teramo, Italy. E-mail: mmaccarrone{at}unite.it
Mammalian reproduction is a complicated process designed todiversify and strengthen the genetic complement of the offspringand to safeguard regulatory systems at various steps for propagatingprocreation. An emerging concept in mammalian reproduction isthe role of endocannabinoids, a group of endogenously producedlipid mediators, that bind to and activate cannabinoid receptors.Although adverse effects of cannabinoids on fertility have beenimplicated for years, the mechanisms by which they exert theseeffects were not clearly understood. With the identificationof cannabinoid receptors, endocannabinoid ligands, their keysynthetic and hydrolytic pathways, and the generation of mousemodels missing cannabinoid receptors, a wealth of informationon the significance of cannabinoid/endocannabinoid signalingin spermatogenesis, fertilization, preimplantation embryo development,implantation, and postimplantation embryonic growth has beengenerated. This review focuses on various aspects of the endocannabinoidsystem in male and female fertility. It is hoped that a deeperinsight would lead to potential clinical applications of theendocannabinoid signaling as a target for correcting infertilityand improving reproductive health in humans.
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