Depletion of bitter taste transduction leads to massive spermatid loss in transgenic mice

Abstract

Bitter taste perception is an important sensory input warning against the ingestion of toxic and noxious substances. Bitter receptors, a family of ~30 highly divergent G-protein-coupled receptors, are exclusively expressed in taste receptor cells that contain the G-protein α-subunit gustducin, bind to α-gustducin in vitro, and respond to bitter tastes in functional expression assays. We generated a taste receptor type 2 member 5 (T2R5)-Cre/green fluorescent protein reporter transgenic mouse to investigate the tissue distribution of T2R5. Our results showed that Cre gene expression in these mice was faithful to the expression of T2R5 in taste tissue. More surprisingly, immunostaining and X-gal staining revealed T2R5 expression in the testis. Ablation of T2R5 + cells led to a smaller testis and removed the spermatid phase from most of the seminiferous tubules. The entire taste transduction cascade (α-gustducin, Ggamma13, phospholipase Cβ2) was detected in spermatogenesis, whereas transient receptor potential, cation channel subfamily M member 5 (Trpm5), was observed only in the later spermatid phase. In short, our results indicate that the taste transduction cascade may be involved in spermatogenesis.

Transient Receptor Potential Channels as Drug Targets: From the Science of Basic Research to the Art of Medicine

“…It is noteworthy that TRPM5 is expressed in taste receptor cells and other chemosensory cells of the taste signaling cascade in the vomeronasal organ, olfactory epithelium, brainstem, enterocrine cells in stomach, duodenum, large intestine, respiratory tract, and pancreatic b cells (see Nilius and Appendino, 2013). Furthermore, TRPM5 expression was reported in the testis, where it is believed to be involved in spermatogenesis (Li and Zhou, 2012).…”

Comprehensive Analysis of Mouse Bitter Taste Receptors Reveals Different Molecular Receptive Ranges for Orthologous Receptors in Mice and Humans

“…In light of findings showing that Tas2r are present in organs that are not at all or only partially accessible to xenobiotics, such as brain (86 -89), testes (61,90,91), thyroid (92), and urethra (93), we also examined whether hormones could function as Tas2r activators. We found that progesterone stimulated Tas2r114 and Tas2r110.…”

“…Mouse spermatids and spermatozoa respond to bitter compounds with calcium signaling in an ␣-gustducin-dependent manner (61). Genetic ablation of bitter receptor cells in mice causes massive spermatid loss (90). Further studies are needed to elucidate the role of this and other Tas2r in testicular function.…”

Taste Receptor Gene Expression Outside the Gustatory System

“…As all 35 mouse bitter taste receptor genes are expressed in the testis and it was shown that mouse spermatids respond to several bitter compounds with increases of intracellular calcium levels [43], it would be highly interesting to see if also bitter taste receptor agonists and antagonists may affect male fertility. The generation of a mouse line, in which all cells that express the bitter taste receptor gene Tas2r105 are genetically ablated by the expression of diphtheria toxin A, revealed a considerable reduction in testicular size [40]. However, this mouse line still produces a reduced number of spermatids including Tas1r3-positive spermatids, suggesting a heterogeneous population of sperm cells.…”

“…It was shown that α-gustducin expression occurs already in differentiating spermatids and is retained in mature spermatozoa [167]. Moreover, also other components of the gustatory signaling cascade, involved in signal transduction of taste GPCRs such as Gγ13, phospholipase Cβ2, and the transient receptor potential channel TRPM5, have been identified in mouse sperm cells [40]. Indeed, expression of all 3 Tas1r genes and all 35 putatively functional Tas2r genes has been detected in mouse testes [43].…”