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Role and Modulation of TRPV1 in Mammalian Spermatozoa: an Updated Review

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Role and Modulation of TRPV1 in Mammalian Spermatozoa: an Updated Review International Journal of Molecular Sciences Review Role and Modulation of TRPV1 in Mammalian Spermatozoa: An Updated Review Marina Ramal-Sanchez 1,*,† , Nicola Bernabò 1,2,† , Luca Valbonetti 1,2 , Costanza Cimini 1, Angela Taraschi 1,3, Giulia Capacchietti 1, Juliana Machado-Simoes 1 and Barbara Barboni 1 1 Faculty of Biosciences and Technology for Food, Agriculture and Environment, University of Teramo, 64100 Teramo, Italy; [email protected] (N.B.); [email protected] (L.V.); [email protected] (C.C.); [email protected] (A.T.); [email protected] (G.C.); [email protected] (J.M.-S.); [email protected] (B.B.) 2 Institute of Biochemistry and Cell Biology (CNR-IBBC/EMMA/Infrafrontier/IMPC), National Research Council, Monterotondo Scalo, 00015 Rome, Italy 3 Istituto Zooprofilattico Sperimentale dell’Abruzzo e del Molise “G. Caporale”, Via Campo Boario 1, 64100 Teramo, Italy * Correspondence: [email protected] † These Authors contributed equally. Abstract: Based on the abundance of scientific publications, the polymodal sensor TRPV1 is known as one of the most studied proteins within the TRP channel family. This receptor has been found in numerous cell types from different species as well as in spermatozoa. The present review is focused on analyzing the role played by this important channel in the post-ejaculatory life of spermatozoa, where it has been described to be involved in events such as capacitation, acrosome reaction, calcium Citation: Ramal-Sanchez, M.; trafficking, sperm migration, and fertilization. By performing an exhaustive bibliographic search, this Bernabò, N.; Valbonetti, L.; Cimini, C.; review gathers, for the first time, all the modulators of the TRPV1 function that, to our knowledge, Taraschi, A.; Capacchietti, G.; were described to date in different species and cell types. Moreover, all those modulators with Machado-Simoes, J.; Barboni, B. Role a relationship with the reproductive process, either found in the female tract, seminal plasma, or and Modulation of TRPV1 in spermatozoa, are presented here. Since the sperm migration through the female reproductive tract is Mammalian Spermatozoa: An one of the most intriguing and less understood events of the fertilization process, in the present work, Updated Review. Int. J. Mol. Sci. 2021, chemotaxis, thermotaxis, and rheotaxis guiding mechanisms and their relationship with TRPV1 22, 4306. https://doi.org/10.3390/ receptor are deeply analyzed, hypothesizing its (in)direct participation during the sperm migration. ijms22094306 Last, TRPV1 is presented as a pharmacological target, with a special focus on humans and some Academic Editor: Elisabeth Pinart pathologies in mammals strictly related to the male reproductive system. Received: 9 March 2021 Keywords: TRPV1; spermatozoa; thermotaxis; chemotaxis; endocannabinoid system; mammals; Accepted: 19 April 2021 human; sperm signaling; ion channel Published: 21 April 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in 1. Introduction published maps and institutional affil- Transient receptor potential vanilloid 1 (TRPV1) is one of the most studied members iations. within the big family of transient receptor potential (TRP) channels. The structure and function of this protein have been widely studied by numerous researchers in order to decipher its exact mechanism of action, although some aspects remain unknown. TRPV1 has been found in multiple cell types, organs, and tissues from different species, and a Copyright: © 2021 by the authors. great number of articles and reviews have investigated and discussed this polymodal Licensee MDPI, Basel, Switzerland. channel [1–4]. TRPV1 acts as a multimodal sensor for numerous physical, chemical, and This article is an open access article mechanical studies by being a key player in signal transduction in multiple processes. distributed under the terms and In the present review, we focused on the role of TRPV1 on spermatozoa physiology af- conditions of the Creative Commons ter ejaculation. This receptor has been shown to participate in multiple events of the sperm Attribution (CC BY) license (https:// functions, such as the acrosome reaction, calcium trafficking, and fertilization. Here, based creativecommons.org/licenses/by/ on exhaustive bibliographic research of international peer-reviewed literature (literature 4.0/). Int. J. Mol. Sci. 2021, 22, 4306. https://doi.org/10.3390/ijms22094306 https://www.mdpi.com/journal/ijms Int. J. Mol. Sci. 2021, 22, x FOR PEER REVIEW 2 of 20 Int. J. Mol. Sci. 2021, 22, 4306 2 of 20 Here, based on exhaustive bibliographic research of international peer-reviewed literature (literature found in the database Scopus), TRPV1, its subfamily vanilloid TRP, and the big TRP family are presented and discussed. The protein structure and its multiple modula- found in the database Scopus), TRPV1, its subfamily vanilloid TRP, and the big TRP family tors found in different cell types and species are reviewed as well. After examining the are presented and discussed. The protein structure and its multiple modulators found modulators of TRPV1 previously described, only the ones found in the reproductive tract, in different cell types and species are reviewed as well. After examining the modulators seminal plasma, or spermatozoa with a potential role in sperm physiology were consid- of TRPV1 previously described, only the ones found in the reproductive tract, seminal ered for further investigation in this review. plasma, or spermatozoa with a potential role in sperm physiology were considered for furtherOne investigation of the most in intriguing this review. events of the post-ejaculatory life of the spermatozoa in the migrationOne of the through most intriguing the female events tract and of thetoward post-ejaculatory the fertilization life site. of the During spermatozoa this trip, inwhich the migrationmay last from through hours the to female days (depending tract and toward on the thespecies) fertilization [5,6], spermatozoa site. During reside this trip,within which the oviduct, may last where from they hours remain to days bound (depending to the oviductal on the species)epithelium [5,6 [7]], spermatozoaor are guided resideby various within stimuli, the oviduct, such as where rheotaxis they (caused remain boundby the toperistaltic the oviductal movements epithelium of the [7 oviduct] or are guidedsmooth bymuscle various and stimuli, the fluid such production), as rheotaxis chemotaxis (caused by(promoted the peristaltic by the movements response to ofchem- the oviductical factors) smooth and muscle thermotaxis and the (induced fluid production), by the gradient chemotaxis of temperature). (promoted by These the response guiding tomechanisms chemical factors) and their and relationship thermotaxis with (induced the TRPV1 by receptor the gradient are also of temperature).examined thoroughly These guidingin this review. mechanisms For instance, and their this relationship channel protein with thehas TRPV1been recently receptor recognized are also examined as a heat- thoroughlysensing receptor in this during review. thermotaxis For instance, in thishumans channel [8]. proteinFinally, has the been use of recently TRPV1 recognized as a phar- asmacological a heat-sensing target receptor in humans during and thermotaxis the incidence in humansof pathologies [8]. Finally, related the to use the of male TRPV1 repro- as aductive pharmacological system in mammals target in humans are explored. and the incidence of pathologies related to the male reproductive system in mammals are explored. 2. TRPV1: Family and Subfamily 2. TRPV1:TRPV1 Family has been and shown Subfamily to be present in numerous tissues and cells of different spe- cies, TRPV1from the has urinary been shown bladder to be [9], present corneal in numerousfibroblasts tissues [10], brain and cells[11], of and different breast species, cancer fromcells the[12], urinary to the bladderreproductive [9], corneal system, fibroblasts as female [10 organs], brain and [11], placenta and breast [13,14]. cancer TRPV1 cells [12 be-], tolongs the reproductiveto the vanilloid system, TRP as subfamily, female organs which and also placenta comprises [13,14 TRPV2,]. TRPV1 TRPV3, belongs TRPV4, to the vanilloidTRPV5, and TRP TRPV6. subfamily, Figure which 1 shows also comprises a graphical TRPV2, phylogenetic TRPV3, TRPV4,reconstruction TRPV5, of and the TRPV6. TRPV Figuresubfamily,1 shows while a graphicalSupplementary phylogenetic Figure S reconstruction1 shows the alignment of the TRPV and phylogenetic subfamily, while recon- Supplementarystruction, performed Figure using S1 shows the function the alignment “build” and of phylogeneticETE3 v3.1.1 [15] reconstruction, as implemented performed on the usingGenomeNet the function (https://www.genome.jp/tools/ete/ “build” of ETE3 v3.1.1 [15] as; implementedaccessed on on20 theApril GenomeNet 2021). Fasta (https: se- //www.genome.jp/tools/ete/quences were obtained from Uni; accessedProtKB on (https://www.uniprot.org/ 20 April 2021). Fasta sequences; accessed were on obtained 20 April from2021) UniProtKB. The tree was (https://www.uniprot.org/ constructed using fasttree ;with accessed slow NNI on 20 and April MLACC=3 2021). The (to treemake was the constructedmaximum-likelihood using fasttree NNIs with more slow exhaustive) NNI and MLACC=3 [16]. Values (to at make nodes the are maximum-likelihood SH-like local sup- NNIsport. more exhaustive) [16]. Values at nodes are SH-like local support. FigureFigure 1.1. HumanHuman TRPVTRPV channel
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