Sperm-Activating Odorous Substances in Human Follicular Fluid and Vaginal Secretion: Identification by Gas Chromatography-Olfactometry and Ca2+ Imaging

• Published in: ChemPlusChem (Weinheim, Germany) Vol. 78; no. 7; pp. 695 - 702
• Main Authors: Hartmann, Constanze, Triller, Annika, Spehr, Marc, Dittrich, Ralf, Hatt, Hanns, Buettner, Andrea
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01.07.2013; WILEY‐VCH Verlag
• Subjects: biological activity; calcium signaling; gas chromatography-olfactometry; membrane proteins; receptors
• ISSN: 2192-6506; 2192-6506
• DOI: 10.1002/cplu.201300008

Human sperm chemotaxis to follicular fluid has been well established, but the molecular mechanism(s) for this phenomenon are still largely unclear. Studies indicate that odorant receptors expressed on spermatozoa could play a role in this scenario. It has recently been shown that several synthetic floral scents activate the receptors OR1D2, OR4D1, and OR7A5 in vitro and evoke distinct sperm motility patterns in vivo. However, all agonists found so far are of synthetic origin and, thus, the presence of endogenous structural analogues in female bodily fluids is subject to speculation. Therefore, the aim of the study reported herein was to investigate the occurrence of odor compounds in vaginal secretions and follicular fluid by using gas chromatography–olfactometry. Chemically identified constituents of either bodily fluid were then analyzed for activation of recombinant chemoreceptors and candidate ligands were further tested for induction of sperm Ca2+ signals. Through using this approach, two novel odorant receptor–ligand pairs are reported and human sperm Ca2+ elevations in response to both odorous substances, namely 5α‐androst‐16‐en‐3‐one and 4‐hydroxy‐2,5‐dimethyl‐3(2H)‐furanone, are shown. Find the egg: Before contact, egg and sperm communicate by chemotaxis. Chemoreceptors expressed on sperm seem to play a key role in this communication (see figure). Several odor‐active ligands for such receptors have been reported in the past, but were exclusively of synthetic origin. Herein, the first endogenous odor‐active ligands are identified in bodily fluids of the female reproductive tract.