Odorant receptors and olfactory-like signaling mechanisms in mammalian sperm
Introduction
The mystery of fertilization has captivated generations of researchers for more than a century, yet our knowledge of many aspects of this fundamental biological process has largely remained rudimentary (reviewed in Vacquier, 1998). As a first step, a million-strong armada of genetically unique sperm cells, readily equipped for the limited purpose of successfully delivering their genetic information to the egg cell, start out on a long journey to locate their target deep inside the female genital tract. This trek represents an enormous navigational challenge to the smallest cells of the human body. To compensate for these difficulties, spermatozoa have developed distinct chemosensory capabilities to scan their environment and allow spatial orientation. Candidate sperm attractants are found widely in aquatic as well as in terrestrial organisms (Riffell et al., 2002). In internal fertilizers, however, the nature and source of such potential chemical guideposts as well as the molecular mechanisms underlying chemically induced changes in sperm motility are controversial questions. In this context, an unexpected group of receptor proteins has recently taken center stage—members of the odorant receptor (OR) family. Conventionally found on ciliary membranes of nasal olfactory sensory neurons (OSNs), the list of potential OR tasks is now significantly extended as various research groups provide evidence that implicates mammalian ORs in sperm–egg chemical communication.
Section snippets
Olfactory signaling—a blueprint for chemodetection in ectopic systems?
The chemical senses, i.e. smell and taste, are ancient sensory modalities that have evolved massive repertoires of receptors to detect and discriminate molecules of immense structural variety. Despite considerable functional differences, all chemosensory receptor proteins currently known belong to the superfamily of G protein-coupled receptors (GPCRs). Receptor activation triggers complex biochemical signaling cascades that transduce the chemical energy of ligand binding into ion fluxes and
Sperm and internal fertilization
From marine broadcast spawners to higher terrestrial vertebrates (including humans), the basic principles of fertilization have been largely conserved. In a remarkably profligate process, several hundred millions of sperm cells are ejaculated to locate the egg either in the turbulent ocean or the relatively benign mammalian reproductive tract. In humans, however, only a small fraction of spermatozoa eventually make their way to the fertilization site, the oviductal ampulla (reviewed in
Odorant receptors and sperm motility
Identification and functional characterization of both a human (Spehr et al., 2003) and a mouse (Fukuda et al., 2004) testicular OR represent major steps toward a deeper understanding of the role ORs play in mammalian sperm. Both receptors, hOR17-4 (synonymous OR1D2) in humans and mOR23 (synonymous mOR267-13) in mice, are activated by small aldehyde molecules and mediate robust Ca2+ signals in mature sperm. Employing multi-level investigational approaches, the physiological functions of these
OR-induced signaling pathway(s) in sperm
Uncovering the mechanistic link between OR activation and characteristic changes in flagellar beating poses a profound scientific challenge. Expression analysis of candidate signal transduction proteins by conventional mRNA-based approaches (i.e. in situ hybridization or RT-PCR) is inapplicable to mature sperm as these cells have shut down their protein synthesis machinery. MudPIT offers a solution to this problem. Combining two-dimensional liquid chromatography and tandem mass spectrometry,
Bifunctionality of sperm ORs
Whether sperm ORs are restricted to reproductive functions or additionally perform their “conventional” task in olfaction is a longstanding question. In favor of a dual function model, mOR23 had originally been identified from lyral-sensitive OSNs (Touhara et al., 1999). Likewise, RT-PCR using intron-spanning primers and subsequent Southern blot analysis revealed expression of hOR17-4 in biopsates of human olfactory epithelium (Spehr et al., 2004a). Although definite proof is lacking,
Perspectives
After years of controversial debate, functional characterization of the first testicular ORs in humans and mice, respectively, should provide long-awaited tools to unravel the mysteries of OR expression in mammalian sperm. In a collaborative effort, various groups now extend their research to this field, legitimating speculation about potential future applications in reproductive medicine. Transferability of current in vitro findings to the in vivo situation, however, awaits conclusive proof.
Acknowledgements
Our work on OR-mediated signaling in sperm is supported by the Emmy Noether Program of the Deutsche Forschungsgemeinschaft (M.S.), by the Heinrich and Alma Vogelsang Foundation (K.S.), by NSF awards IBN 01-32635 and IBN 02-06775, as well as grants from the UCLA Council on Research, and NOAA California Sea Grant College Program R/F-197 (R.K.Z.), and by the University of Arizona Center for Insect Science NIH training grant No. 1K126M00708 (J.A.R.).
We thank Thomas Lichtleitner for preparing
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