Abstract
Taste receptors (TASRs) are expressed not only in the oral cavity but also throughout the body, thus suggesting that they may play different roles in organ systems beyond the tongue. Recent studies showed the expression of several TASRs in mammalian testis and sperm, indicating an involvement of these receptors in male gametogenesis and fertility. This notion is supported by an impaired reproductive phenotype of mouse carrying targeted deletion of taste receptor genes, as well as by a significant correlation between human semen parameters and specific polymorphisms of taste receptor genes. To better understand the biological and thus clinical significance of these receptors for human reproduction, we analyzed the expression of several members of the TAS2Rs family of bitter receptors in human testis and in ejaculated sperm before and after in vitro selection and capacitation. Our results provide evidence for the expression of TAS2R genes, with TAS2R14 being the most expressed bitter receptor subtype in both testis tissue and sperm cells, respectively. In addition, it was observed that in vitro capacitation significantly affects both the expression and the subcellular localization of these receptors in isolated spermatozoa. Interestingly, α-gustducin and α-transducin, two Gα subunits expressed in taste buds on the tongue, are also expressed in human spermatozoa; moreover, a subcellular redistribution of both G protein α-subunits to different sub-compartments of sperm was registered upon in vitro capacitation. Finally, we shed light on the possible downstream transduction pathway initiated upon taste receptor activation in the male reproductive system. Performing ultrasensitive droplets digital PCR assays to quantify RNA copy numbers of a distinct gene, we found a significant correlation between the expression of TAS2Rs and TRPM5 (r = 0.87), the cation channel involved in bitter but also sweet and umami taste transduction in taste buds on the tongue. Even if further studies are needed to clarify the precise functional role of taste receptors for successful reproduction, the presented findings significantly extend our knowledge of the biological role of TAS2Rs for human male fertility.
Highlights
The designation “taste receptors” (TASRs) initially derives from the first identification of TASRs in small clusters of specialized epithelial cells on the tongue, called taste buds [1]
Taste Receptor Expression in Human Sperm and Testis Tissue Droplets digital polymerase chain reaction (ddPCR) was carried out in order to determine the relative expression of selected taste genes belonging to the TAS2R family in human sperm collected from 15 normozoospermic men, whose main sperm parameters resulted within the range of normality, according to WHO criteria [31]: sperm concentration was 32.7 × 106, total sperm motility was 53%, and typical morphology was 7%
In light of these pleiotropic activities, it has been supposed that taste receptors in the male reproductive system may be involved in controlling male fertility, probably during the processes of spermatogenesis, epididymal sperm maturation, sperm’s migration through the female genital tract, and/or upon final sperm egg fusion [48]
Summary
The designation “taste receptors” (TASRs) initially derives from the first identification of TASRs in small clusters of specialized epithelial cells on the tongue, called taste buds [1]. Numerous studies published in recent years point the attention on the expression of TASRs throughout the body, both in humans and in animals [2]. Their expression has been reported, among others, in the respiratory [3] and digestive [4] systems, in brain [5], as well as in testis [6,7,8,9]. The gustatory system can discriminate five distinct taste modalities: sweet, bitter, salty, sour, and umami. Salty and sour tastes are both directly sensed by ion channels [10,11], whereas umami, sweet, and bitter taste stimuli are recognized by G protein-coupled receptors (GPCRs) [1,12,13]. TAS1Rs are responsible for perceiving sweet compounds and umami, defined as the taste of monosodium glutamate [16,17], whereas TAS2Rs are operative in detecting the vast variety of bitter molecules, both natural and synthetic [15,18,19,20]
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