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Identification of a Testicular Odorant Receptor Mediating Human Sperm Chemotaxis

Science, 28 March 2003
Vol. 299, Issue 5615, p. 2054-2058
DOI: 10.1126/science.1080376

Identification of a Testicular Odorant Receptor Mediating Human Sperm Chemotaxis

  1. Marc Spehr1,
  2. Günter Gisselmann1,
  3. Alexandra Poplawski1,
  4. Jeffrey A. Riffell2,
  5. Christian H. Wetzel1,
  6. Richard K. Zimmer2,3,
  7. Hanns Hatt1,*
  1. 1 Department of Cell Physiology, Ruhr University Bochum, 150 University Street, D-44780 Bochum, Germany.
  2. 2 Department of Biology,
  3. 3 Neurosciences Program and Brain Research Institute, University of California, 621 Young Drive South, Los Angeles, CA 90095, USA.

Abstract

Although it has been known for some time that olfactory receptors (ORs) reside in spermatozoa, the function of these ORs is unknown. Here, we identified, cloned, and functionally expressed a previously undescribed human testicular OR, hOR17-4. With the use of ratiofluorometric imaging, Ca2+ signals were induced by a small subset of applied chemical stimuli, establishing the molecular receptive fields for the recombinantly expressed receptor in human embryonic kidney (HEK) 293 cells and the native receptor in human spermatozoa. Bourgeonal was a powerful agonist for both recombinant and native receptor types, as well as a strong chemoattractant in subsequent behavioral bioassays. In contrast, undecanal was a potent OR antagonist to bourgeonal and related compounds. Taken together, these results indicate that hOR17-4 functions in human sperm chemotaxis and may be a critical component of the fertilization process.

  • * To whom correspondence should be addressed. E-mail: hanns.hatt{at}ruhr-uni-bochum.de

  • Received for publication 12 November 2002.
  • Accepted for publication 22 January 2003.

Citation:

M. Spehr, G. Gisselmann, A. Poplawski, J. A. Riffell, C. H. Wetzel, R. K. Zimmer, and H. Hatt, Identification of a Testicular Odorant Receptor Mediating Human Sperm Chemotaxis. Science 299, 2054-2058 (2003).

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elife 3, e02403-e02403 (1 January 2014)

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R. S. Tavares, S. Mansell, C. L. R. Barratt, S. M. Wilson, S. J. Publicover, and J. Ramalho-Santos
Hum Reprod 28, 3167-3177 (1 December 2013)

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J. L. Pluznick, S. Mansell, C. L. R. Barratt, S. M. Wilson, S. J. Publicover, and J. Ramalho-Santos
Am. J. Physiol. Renal Physiol. 305, F439-F444 (15 August 2013)

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M. Yoshida, Y. Hiradate, N. Sensui, J. Cosson, and M. Morisawa
Biol. Bull. 224, 156-165 (1 August 2013)

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C. Sinding, E. Kemper, P. Spornraft-Ragaller, and T. Hummel
Chem Senses 38, 439-445 (1 June 2013)

Olfactory receptor responding to gut microbiota-derived signals plays a role in renin secretion and blood pressure regulation
J. L. Pluznick, R. J. Protzko, H. Gevorgyan, Z. Peterlin, A. Sipos, J. Han, I. Brunet, L.-X. Wan, F. Rey, T. Wang et al.
Proc. Natl. Acad. Sci. USA 110, 4410-4415 (12 March 2013)

Functional characterization of bitter-taste receptors expressed in mammalian testis
J. Xu, J. Cao, N. Iguchi, D. Riethmacher, and L. Huang
Mol Hum Reprod 19, 17-28 (1 January 2013)

The CatSper channel: a polymodal chemosensor in human sperm
C. Brenker, N. Goodwin, I. Weyand, N. D. Kashikar, M. Naruse, M. Krahling, A. Muller, U. B. Kaupp, and T. Strunker
EMBO J. 31, 1654-1665 (4 April 2012)

Regulation of behaviorally associated gene networks in worker honey bee ovaries
Y. Wang, S. D. Kocher, T. A. Linksvayer, C. M. Grozinger, R. E. Page, and G. V. Amdam
J. Exp. Biol. 215, 124-134 (1 January 2012)

Calcium Channels in the Development, Maturation, and Function of Spermatozoa
A. Darszon, T. Nishigaki, C. Beltran, and C. L. Trevino
Physiol. Rev. 91, 1305-1355 (1 October 2011)

cAMP and IP3 Signaling Pathways in HEK293 Cells Transfected with Canine Olfactory Receptor Genes
N. Benbernou, S. Robin, S. Tacher, M. Rimbault, M. Rakotomanga, and F. Galibert
J Hered 102, S47-S61 (1 September 2011)

Sperm chemotaxis, fluid shear, and the evolution of sexual reproduction
R. K. Zimmer, and J. A. Riffell
Proc. Natl. Acad. Sci. USA 108, 13200-13205 (9 August 2011)

Sperm chemotaxis and regulation of flagellar movement by Ca2+
M. Yoshida, and K. Yoshida
Mol Hum Reprod 17, 457-465 (1 August 2011)

Sperm motility: is viscosity fundamental to progress?
J. C. Kirkman-Brown, and D. J. Smith
Mol Hum Reprod 17, 539-544 (1 August 2011)

Mathematical modeling of calcium signaling during sperm hyperactivation
S. D. Olson, L. J. Fauci, and S. S. Suarez
Mol Hum Reprod 17, 500-510 (1 August 2011)

Chemosensory Ca2+ Dynamics Correlate with Diverse Behavioral Phenotypes in Human Sperm
T. Veitinger, J. R. Riffell, S. Veitinger, J. M. Nascimento, A. Triller, C. Chandsawangbhuwana, K. Schwane, A. Geerts, F. Wunder, M. W. Berns et al.
J Biol Chem 286, 17311-17325 (13 May 2011)

Drosophila Sperm Motility in the Reproductive Tract
Y. Yang, and X. Lu
Biol. Reprod. 84, 1005-1015 (1 May 2011)

Temporal coding of odor mixtures in an olfactory receptor neuron
C.-Y. Su, C. Martelli, T. Emonet, and J. R. Carlson
Proc. Natl. Acad. Sci. USA 108, 5075-5080 (22 March 2011)

Rethinking the Relationship Between Hyperactivation and Chemotaxis in Mammalian Sperm
H. Chang, and S. S. Suarez
Biol. Reprod. 83, 507-513 (1 October 2010)

Odorant-Specific Modes of Signaling in Mammalian Olfaction
B. W. Ache, and S. S. Suarez
Chem Senses 35, 533-539 (1 September 2010)

Human Male Superiority in Olfactory Sensitivity to the Sperm Attractant Odorant Bourgeonal
P. Olsson, and M. Laska
Chem Senses 35, 427-432 (1 June 2010)

Calcium Signaling Through CatSper Channels in Mammalian Fertilization
D. Ren, and J. Xia
Physiology 25, 165-175 (1 June 2010)

Evolution and spermatogenesis
H. White-Cooper, and N. Bausek
Phil Trans R Soc B 365, 1465-1480 (27 May 2010)

Human Sperm Thermotaxis Is Mediated by Phospholipase C and Inositol Trisphosphate Receptor Ca2+ Channel
A. Bahat, and M. Eisenbach
Biol. Reprod. 82, 606-616 (1 March 2010)

Dual Activities of Odorants on Olfactory and Nuclear Hormone Receptors
H. Pick, S. Etter, O. Baud, R. Schmauder, L. Bordoli, T. Schwede, and H. Vogel
J Biol Chem 284, 30547-30555 (30 October 2009)

Molecular Tuning of Odorant Receptors and Its Implication for Odor Signal Processing
J. Reisert, and D. Restrepo
Chem Senses 34, 535-545 (1 September 2009)

Odor Interaction between Bourgeonal and Its Antagonist Undecanal
M. Brodin, M. Laska, and M. J. Olsson
Chem Senses 34, 625-630 (1 September 2009)

Large-scale production and study of a synthetic G protein-coupled receptor: Human olfactory receptor 17-4
B. L. Cook, D. Steuerwald, L. Kaiser, J. Graveland-Bikker, M. Vanberghem, A. P. Berke, K. Herlihy, H. Pick, H. Vogel, S. Zhang et al.
Proc. Natl. Acad. Sci. USA 106, 11925-11930 (21 July 2009)

Activation of an Olfactory Receptor Inhibits Proliferation of Prostate Cancer Cells
E. M. Neuhaus, W. Zhang, L. Gelis, Y. Deng, J. Noldus, and H. Hatt
J Biol Chem 284, 16218-16225 (12 June 2009)

Behavioral response of human spermatozoa to a concentration jump of chemoattractants or intracellular cyclic nucleotides
A. Gakamsky, L. Armon, and M. Eisenbach
Hum Reprod 24, 1152-1163 (1 May 2009)

Endogenous signaling pathways and chemical communication between sperm and egg
P. J. Krug, J. A. Riffell, and R. K. Zimmer
J. Exp. Biol. 212, 1092-1100 (15 April 2009)

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O. De la Cruz, R. Blekhman, X. Zhang, D. Nicolae, S. Firestein, and Y. Gilad
Mol Biol Evol 26, 491-494 (1 March 2009)

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J. L. Pluznick, D.-J. Zou, X. Zhang, Q. Yan, D. J. Rodriguez-Gil, C. Eisner, E. Wells, C. A. Greer, T. Wang, S. Firestein et al.
Proc. Natl. Acad. Sci. USA 106, 2059-2064 (10 February 2009)

Control of hyperactivation in sperm
S. S. Suarez, D.-J. Zou, X. Zhang, Q. Yan, D. J. Rodriguez-Gil, C. Eisner, E. Wells, C. A. Greer, T. Wang, S. Firestein et al.
Hum Reprod Update 14, 647-657 (1 November 2008)

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S. S. Steiger, A. E. Fidler, and B. Kempenaers
J Hered 99, 624-628 (1 November 2008)

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L. Kaiser, J. Graveland-Bikker, D. Steuerwald, M. Vanberghem, K. Herlihy, and S. Zhang
Proc. Natl. Acad. Sci. USA 105, 15726-15731 (14 October 2008)

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M. S. Teng, P. Shadbolt, A. G. Fraser, G. Jansen, and J. McCafferty
Proc. Natl. Acad. Sci. USA 105, 14826-14831 (30 September 2008)

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G. Sanz, T. Thomas-Danguin, E. H. Hamdani, C. Le Poupon, L. Briand, J.-C. Pernollet, E. Guichard, and A. Tromelin
Chem Senses 33, 639-653 (1 September 2008)

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N. Benbernou, S. Tacher, S. Robin, M. Rakotomanga, F. Senger, and F. Galibert
J Hered 0, esm054v2- (3 August 2007)

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Y. Choi, Y. Qin, M. F. Berger, D. J. Ballow, M. L. Bulyk, and A. Rajkovic
Biol. Reprod. 77, 312-319 (1 August 2007)

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H. M. Florman, M. K. Jungnickel, and K. A. Sutton
Proc. Natl. Acad. Sci. USA 104, 11123-11124 (3 July 2007)

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M. F. Bhutta, M. K. Jungnickel, and K. A. Sutton
J R Soc Med 100, 268-274 (1 June 2007)

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H. Zhuang, and H. Matsunami
J Biol Chem 282, 15284-15293 (18 May 2007)

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B. Baibakov, L. Gauthier, P. Talbot, T. L. Rankin, and J. Dean
Development 134, 933-943 (1 March 2007)

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A. Mashukova, M. Spehr, H. Hatt, and E. M. Neuhaus
J. Neurosci. 26, 9902-9912 (27 September 2006)

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E. M. Neuhaus, A. Mashukova, J. Barbour, D. Wolters, and H. Hatt
J. Cell Sci. 119, 3047-3056 (1 August 2006)

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L. E. C. Von Dannecker, A. F. Mercadante, and B. Malnic
Proc. Natl. Acad. Sci. USA 103, 9310-9314 (13 June 2006)

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E. M. Neuhaus, A. Mashukova, W. Zhang, J. Barbour, and H. Hatt
Chem Senses 31, 445-452 (1 June 2006)

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C. Jimenez-Gonzalez, F. Michelangeli, C.V. Harper, C.L.R. Barratt, and S.J. Publicover
Hum Reprod Update 12, 253-267 (1 May 2006)

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S. M. Schuh, A. E. Carlson, G. S. McKnight, M. Conti, B. Hille, and D. F. Babcock
Biol. Reprod. 74, 492-500 (1 March 2006)

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S.S. Suarez, and A. A. Pacey
Hum Reprod Update 12, 23-37 (1 January 2006)

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M. Bajpai, S. E. Fiedler, Z. Huang, S. Vijayaraghavan, G. E. Olson, G. Livera, M. Conti, and D. W. Carr
Biol. Reprod. 74, 109-118 (1 January 2006)

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C. V. Harper, and S. J. Publicover
Hum Reprod 20, 2675-2680 (1 October 2005)

Ca2+ spikes in the flagellum control chemotactic behavior of sperm
M. Bohmer, Q. Van, I. Weyand, V. Hagen, M. Beyermann, M. Matsumoto, M. Hoshi, E. Hildebrand, and U. B. Kaupp
EMBO J. 24, 2741-2752 (3 August 2005)

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M. Kosinski, K. McDonald, J. Schwartz, I. Yamamoto, and D. Greenstein
Development 132, 3357-3369 (1 August 2005)

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C. D. Wood, T. Nishigaki, T. Furuta, S. A. Baba, and A. Darszon
JCB 169, 725-731 (6 June 2005)

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E. Shirokova, K. Schmiedeberg, P. Bedner, H. Niessen, K. Willecke, J.-D. Raguse, W. Meyerhof, and D. Krautwurst
J Biol Chem 280, 11807-11815 (25 March 2005)

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F. Sun, A. Bahat, A. Gakamsky, E. Girsh, N. Katz, L. C. Giojalas, I. Tur-Kaspa, and M. Eisenbach
Hum Reprod 20, 761-767 (1 March 2005)

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N. Chen, S. Pai, Z. Zhao, A. Mah, R. Newbury, R. C. Johnsen, Z. Altun, D. G. Moerman, D. L. Baillie, L. D. Stein et al.
Proc. Natl. Acad. Sci. USA 102, 146-151 (4 January 2005)

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G. Sanz, C. Schlegel, J.-C. Pernollet, and L. Briand
Chem Senses 30, 69-80 (1 January 2005)

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N. Fukuda, K. Yomogida, M. Okabe, and K. Touhara
J. Cell Sci. 117, 5835-5845 (15 November 2004)

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Y. Oka, A. Nakamura, H. Watanabe, and K. Touhara
Chem Senses 29, 815-822 (1 November 2004)

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C. V. Harper, C. L. R. Barratt, and S. J. Publicover
J Biol Chem 279, 46315-46325 (29 October 2004)

High-throughput microarray detection of olfactory receptor gene expression in the mouse
X. Zhang, M. Rogers, H. Tian, X. Zhang, D.-J. Zou, J. Liu, M. Ma, G. M. Shepherd, and S. J. Firestein
Proc. Natl. Acad. Sci. USA 101, 14168-14173 (28 September 2004)

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M. Spehr, K. Schwane, J. A. Riffell, J. Barbour, R. K. Zimmer, E. M. Neuhaus, and H. Hatt
J Biol Chem 279, 40194-40203 (17 September 2004)

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M. Eisenbach, K. Schwane, J. A. Riffell, J. Barbour, R. K. Zimmer, E. M. Neuhaus, and H. Hatt
JGP 124, 105-108 (26 July 2004)

Olfactory Receptor Neuron Profiling using Sandalwood Odorants
S. Bieri, K. Monastyrskaia, and B. Schilling
Chem Senses 29, 483-487 (1 July 2004)

Control of Male Gametophyte Development
S. McCormick, K. Monastyrskaia, and B. Schilling
Plant Cell 16, S142-S153 (1 June 2004)

Paracrine regulation of mammalian oocyte maturation and male germ cell survival
K. Kawamura, J. Kumagai, S. Sudo, S.-Y. Chun, M. Pisarska, H. Morita, J. Toppari, P. Fu, J. D. Wade, R. A. D. Bathgate et al.
Proc. Natl. Acad. Sci. USA 101, 7323-7328 (11 May 2004)

Evolution and Comparative Genomics of Odorant- and Pheromone-Associated Genes in Rodents
R. D. Emes, S. A. Beatson, C. P. Ponting, and L. Goodstadt
Genome Res 14, 591-602 (1 April 2004)

The human olfactory receptor gene family
B. Malnic, P. A. Godfrey, and L. B. Buck
Proc. Natl. Acad. Sci. USA 101, 2584-2589 (24 February 2004)

The mouse olfactory receptor gene family
P. A. Godfrey, B. Malnic, and L. B. Buck
Proc. Natl. Acad. Sci. USA 101, 2156-2161 (17 February 2004)

Expression of fractalkine in the Fallopian tube and of CX3CR1 in sperm
Q. Zhang, K. Shimoya, K. Temma, T. Kimura, T. Tsujie, M. Shioji, K. Wasada, O. Fukui, S. Hayashi, T. Kanagawa et al.
Hum Reprod 19, 409-414 (1 February 2004)

Olfactory receptor antagonism between odorants
Y. Oka, M. Omura, H. Kataoka, and K. Touhara
EMBO J. 23, 120-126 (14 January 2004)

First messenger regulation of capacitation via G protein-coupled mechanisms: a tale of serendipity and discovery
L. R. Fraser, S. A. Adeoya-Osiguwa, and R. W. Baxendale
Mol Hum Reprod 9, 739-748 (1 December 2003)

Understanding the chemistry of chemical communication: Are we there yet?
J. Meinwald, S. A. Adeoya-Osiguwa, and R. W. Baxendale
Proc. Natl. Acad. Sci. USA 100, 14514-14516 (25 November 2003)

Evolution of olfactory receptor genes in the human genome
Y. Niimura, and M. Nei
Proc. Natl. Acad. Sci. USA 100, 12235-12240 (14 October 2003)

SNIFFING SPERM
H. Merzendorfer, and M. Nei
J. Exp. Biol. 206, 2528-2528 (1 August 2003)

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