Endocrine Abstracts

Fertilization is still one of the nature’s best-kept secrets. Despite a century of research we still lack a comprehensive understanding how mammalian sperm cells navigate inside the female body, locate, and finally fertilize the egg. More than a decade ago, the unexpected finding of olfactory receptor expression in human testicular tissue led to speculation about a potential role of these chemoreceptors in various aspects of mature sperm behavior, especially sperm chemotaxis. We could obtain first evidence in favor of this hypothesis by the identification of hOR17-4, a testicular olfactory receptor that mediates human sperm chemotaxis. We showed that in vitro activation of the receptor hOR17-4 by a variety of floral odorants (e.g. bourgeonal, cyclamal) mediates both chemotaxis and chemokinesis in human sperm cells. A detailed characterization of the receptor’s molecular receptive range as well as the first description of a potent receptor antagonist could provide the basis for future applications in fertility treatment with important consequences in contraception. Very recently we reported cloning, recombinant expression and functional characterization of another human testicular olfactory receptor (hOR17-2). Using a combination of imaging behavioral assays, we showed activation of sperm by cognate receptor ligands and described a specific receptor-mediated motility pattern. Comparative analysis of different OR-induced signaling pathways as well as cell-specific receptor expression profiles are subject of current research. Given an estimated number of up to 40 different testiculary expressed odorant receptors, an identification of the stimulatory ligands of further members of this “unconventional” group of ORs is critical to gain new insight in their role in reproduction.