{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T13:46:35Z","timestamp":1791812795807,"version":"4.3.4"},"reference-count":107,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2020,10,26]],"date-time":"2020-10-26T00:00:00Z","timestamp":1603670400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The renin-angiotensin system (RAS) is a peptidic system known mainly for its roles in the maintenance of blood pressure and electrolyte and fluid homeostasis. However, several tissues and cells have been described to possess an intrinsic RAS that acts locally through different paracrine and autocrine mechanisms. In the male reproductive system, several components of this system have been observed in various organs and tissues, such as the testes, spermatozoa and seminal fluid. Some functions attributed to this local RAS are maintenance of seminal plasma electrolytes, regulation of steroidogenesis and spermatogenesis, and sperm functions. However, their specific actions in these locations are not fully understood. Therefore, a deep knowledge of the functions of the RAS at both the testicular and seminal levels could clarify its roles in male infertility and sperm physiology, and the different RAS elements could be used to design tools enabling the diagnosis and\/or treatment of male infertility.<\/jats:p>","DOI":"10.3390\/ijms21217943","type":"journal-article","created":{"date-parts":[[2020,10,26]],"date-time":"2020-10-26T10:38:35Z","timestamp":1603708715000},"page":"7943","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Regulation of Male Fertility by the Renin-Angiotensin System"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2351-4955","authenticated-orcid":false,"given":"Marta","family":"Gianzo","sequence":"first","affiliation":[{"name":"Department of Physiology, Faculty of Medicine and Nursery, University of the Basque Country (UPV\/EHU), 48940 Leioa, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nerea","family":"Subir\u00e1n","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine and Nursery, University of the Basque Country (UPV\/EHU), 48940 Leioa, Spain"},{"name":"Innovation in Assisted Reproduction Group, Biocruces-Bizkaia Health Research Institute, 48903 Barakaldo, Spain"},{"name":"Research and Development Department, MEPRO Medical Reproductive Solutions, 20009 San Sebastian, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"R159","DOI":"10.1530\/REP-15-0261","article-title":"Genetics of male infertility: From research to clinic","volume":"150","author":"Krausz","year":"2015","journal-title":"Reproduction"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1111\/j.1442-2042.2010.02619.x","article-title":"New Generation of Diagnostic Tests for Infertility: Review of Specialized Semen Tests","volume":"17","author":"Samplaski","year":"2010","journal-title":"Int. J. Urol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/aja.2010.101","article-title":"Mouse Models in Male Fertility Research","volume":"13","author":"Jamsai","year":"2011","journal-title":"Asian J. Androl."},{"key":"ref_4","first-page":"259","article-title":"Regulation of Spermatogenesis by paracrine\/autocrine Testicular Factors","volume":"6","author":"Huleihel","year":"2004","journal-title":"Asian J. Androl."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Simoni, M., and Huhtaniemi, I.T. (2017). Testicular Steroidogenesis. Endocrinology of the Testis and Male Reproduction, Springer.","DOI":"10.1007\/978-3-319-44441-3"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1152\/physrev.00036.2005","article-title":"Physiology of Local Renin-Angiotensin Systems","volume":"86","author":"Paul","year":"2006","journal-title":"Physiol. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"150","DOI":"10.3389\/fendo.2013.00150","article-title":"Local Renin-Angiotensin System in the Reproductive System","volume":"4","author":"Herr","year":"2013","journal-title":"Front. Endocrinol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1677\/jme.0.0300263","article-title":"The Renin-Angiotensin System and Male Reproduction: New Functions for Old Hormones","volume":"30","author":"Leung","year":"2003","journal-title":"J. Mol. Endocrinol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1046\/j.1439-0272.2003.00535.x","article-title":"Isoforms of Angiotensin I-Converting Enzyme in the Development and Differentiation of Human Testis and Epididymis","volume":"35","author":"Pauls","year":"2003","journal-title":"Andrologia"},{"key":"ref_10","first-page":"415","article-title":"International Union of Pharmacology. XXIII. The Angiotensin II Receptors","volume":"52","author":"Catt","year":"2000","journal-title":"Pharmacol. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1038\/nrc2945","article-title":"The Renin-Angiotensin System and Cancer: Old Dog, New Tricks","volume":"10","author":"George","year":"2010","journal-title":"Nat. Rev. Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1172\/JCI0214276","article-title":"Pivotal Role of the renin\/prorenin Receptor in Angiotensin II Production and Cellular Responses to Renin","volume":"109","author":"Nguyen","year":"2002","journal-title":"J. Clin. Investig."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1111\/j.1365-2796.2008.01981.x","article-title":"Renin-Angiotensin System Revisited","volume":"264","author":"Fyhrquist","year":"2008","journal-title":"J. Intern. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1161\/01.HYP.0000082495.93495.5B","article-title":"Intracellular Renin and the Nature of Intracrine Enzymes","volume":"42","author":"Re","year":"2003","journal-title":"Hypertension"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.tem.2007.05.001","article-title":"The Intracellular Renin-Angiotensin System: A New Paradigm","volume":"18","author":"Kumar","year":"2007","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Chappell, M.C., Marshall, A.C., Alzayadneh, E.M., Shaltout, H.A., and Diz, D.I. (2014). Update on the Angiotensin Converting Enzyme 2-Angiotensin (1\u20137)-Mas Receptor Axis: Fetal Programing, Sex Differences, and Intracellular Pathways. Front. Endocrinol., 4.","DOI":"10.3389\/fendo.2013.00201"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1093\/humrep\/12.4.651","article-title":"Tissue Renin-Angiotensin Systems and Reproduction","volume":"12","author":"Vinson","year":"1997","journal-title":"Hum. Reprod."},{"key":"ref_18","unstructured":"Fontes, P.K. (2017). Renin-Angiotensin System on Reproductive Biology. Renin-Angiotensin System, IntechOpen."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1038\/hr.2009.74","article-title":"Devil and Angel in the Renin-Angiotensin System: ACE-Angiotensin II-AT1 Receptor Axis Vs. ACE2-Angiotensin-(1\u20137)-Mas Receptor Axis","volume":"32","author":"Iwai","year":"2009","journal-title":"Hypertens. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"R1","DOI":"10.1530\/JOE-12-0341","article-title":"Angiotensin-Converting Enzyme 2, Angiotensin-(1\u20137) and Mas: New Players of the Renin-Angiotensin System","volume":"216","author":"Santos","year":"2013","journal-title":"J. Endocrinol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"48623","DOI":"10.1074\/jbc.C100512200","article-title":"Evidence that the Angiotensin IV (AT(4)) Receptor is the Enzyme Insulin-Regulated Aminopeptidase","volume":"276","author":"Albiston","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1042\/CS20100432","article-title":"Renin, (Pro)Renin and Receptor: An Update","volume":"120","author":"Nguyen","year":"2011","journal-title":"Clin. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/s002329900219","article-title":"Angiotensin II Receptors: Localization of Type I and Type II in Rat Epididymides of Different Developmental Stages","volume":"157","author":"Leung","year":"1997","journal-title":"J. Membr. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S0303-7207(99)00107-0","article-title":"Angiotensinogen Expression by Rat Epididymis: Evidence for an Intrinsic, Angiotensin-Generating System","volume":"155","author":"Leung","year":"1999","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1159\/000139322","article-title":"Characterization of Contractile Response to Angiotensin in Epididymal Rat Vas Deferens","volume":"51","author":"Sum","year":"1995","journal-title":"Pharmacology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1210\/endo.142.3.8020","article-title":"Identification, Distribution, and Expression of Angiotensin II Receptors in the Normal Human Prostate and Benign Prostatic Hyperplasia","volume":"142","author":"Dinh","year":"2001","journal-title":"Endocrinology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1093\/humrep\/15.6.1345","article-title":"Angiotensin II in Human Seminal Fluid","volume":"15","author":"Djahanbahkch","year":"2000","journal-title":"Hum. Reprod."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/S0196-9781(01)00622-2","article-title":"Peptidase Activities in Human Semen","volume":"23","author":"Fernandez","year":"2002","journal-title":"Peptides"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1002\/j.1939-4640.2004.tb02848.x","article-title":"Enkephalin-Degrading Enzymes in Normal and Subfertile Human Semen","volume":"25","author":"Irazusta","year":"2004","journal-title":"J. Androl."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"29","DOI":"10.3109\/01485018808986730","article-title":"Induction of Renin-Angiotensin System in Human Testis in Vivo","volume":"21","author":"Okuyama","year":"1988","journal-title":"Arch. Androl."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1038\/aja.2010.82","article-title":"Control of APN\/CD13 and NEP\/CD10 on Sperm Motility","volume":"12","author":"Subiran","year":"2010","journal-title":"Asian J. Androl."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1007\/s10735-010-9264-8","article-title":"Angiotensin (1\u20137) and its Receptor Mas are Expressed in the Human Testis: Implications for Male Infertility","volume":"41","author":"Reis","year":"2010","journal-title":"J. Mol. Histol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1016\/j.fertnstert.2015.11.004","article-title":"Angiotensin II Type 2 Receptor is Expressed in Human Sperm Cells and is Involved in Sperm Motility","volume":"105","author":"Gianzo","year":"2016","journal-title":"Fertil. Steril."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2334","DOI":"10.1210\/endo-120-6-2334","article-title":"A Comparative Study of the Distributions of Renin and Angiotensinogen Messenger Ribonucleic Acids in Rat and Mouse Tissues","volume":"120","author":"Dzau","year":"1987","journal-title":"Endocrinology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1016\/0006-291X(84)91238-5","article-title":"Evidence for Intracellular Formation of Angiotensins: Coexistence of Renin and Angiotensin-Converting Enzyme in Leydig Cells of Rat Testis","volume":"122","author":"Pandey","year":"1984","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1016\/0006-291X(84)90590-4","article-title":"Detection of Renin mRNA in Mouse Testis by Hybridization with Renin cDNA Probe","volume":"125","author":"Pandey","year":"1984","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"7552","DOI":"10.1073\/pnas.83.19.7552","article-title":"Analysis by Immunocytochemistry and in Situ Hybridization of Renin and its mRNA in Kidney, Testis, Adrenal, and Pituitary of the Rat","volume":"83","author":"Deschepper","year":"1986","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1210\/endo-112-4-1318","article-title":"Pituitary-Dependent Renin-Like Immunoreactivity in the Rat Testis","volume":"112","author":"Parmentier","year":"1983","journal-title":"Endocrinology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"337","DOI":"10.3181\/00379727-177-41953","article-title":"Gonadotropin-Dependent Renin in the Rat Testes","volume":"177","author":"Naruse","year":"1984","journal-title":"Proc. Soc. Exp. Biol. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S0167-0115(98)00141-4","article-title":"Angiotensin II: A Reproductive Hormone Too?","volume":"79","author":"Speth","year":"1999","journal-title":"Regul. Pept."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3934","DOI":"10.1016\/S0021-9258(17)35604-1","article-title":"Regulation of Renin Angiotensins by Gonadotropic Hormones in Cultured Murine Leydig Tumor Cells. Release of Angiotensin but Not Renin","volume":"261","author":"Pandey","year":"1986","journal-title":"J. Biol. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/0005-2744(71)90142-2","article-title":"Concentrations of Angiotensin-Converting Enzyme in Tissues of the Rat","volume":"250","author":"Cushman","year":"1971","journal-title":"Biochim. Biophys. Acta Enzymol."},{"key":"ref_43","first-page":"18","article-title":"Sperm-Specific Expression of Angiotensin-Converting Enzyme (ACE) is Mediated by a 91-Base-Pair Promoter Containing a CRE-Like Element","volume":"13","author":"Howard","year":"1993","journal-title":"Mol. Cell. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"9386","DOI":"10.1073\/pnas.85.24.9386","article-title":"Two Putative Active Centers in Human Angiotensin I-Converting Enzyme Revealed by Molecular Cloning","volume":"85","author":"Soubrier","year":"1988","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"7741","DOI":"10.1073\/pnas.86.20.7741","article-title":"Molecular Cloning of Human Testicular Angiotensin-Converting Enzyme: The Testis Isozyme is Identical to the C-Terminal Half of Endothelial Angiotensin-Converting Enzyme","volume":"86","author":"Ehlers","year":"1989","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"11945","DOI":"10.1016\/S0021-9258(18)80158-2","article-title":"Mouse Angiotensin-Converting Enzyme is a Protein Composed of Two Homologous Domains","volume":"264","author":"Bernstein","year":"1989","journal-title":"J. Biol. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"15377","DOI":"10.1016\/S0021-9258(18)98626-6","article-title":"Structure of the Angiotensin I-Converting Enzyme Gene. Two Alternate Promoters Correspond to Evolutionary Steps of a Duplicated Gene","volume":"266","author":"Hubert","year":"1991","journal-title":"J. Biol. Chem."},{"key":"ref_48","first-page":"4294","article-title":"Transcription of Testicular Angiotensin-Converting Enzyme (ACE) is Initiated within the 12th Intron of the Somatic ACE Gene","volume":"10","author":"Howard","year":"1990","journal-title":"Mol. Cell. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"15559","DOI":"10.1016\/S0021-9258(18)98437-1","article-title":"Transgenic Mice Demonstrate a Testis-Specific Promoter for Angiotensin-Converting Enzyme","volume":"266","author":"Langford","year":"1991","journal-title":"J. Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1016\/0024-3205(85)90362-5","article-title":"Testicular Angiotensin I-Converting Enzyme (E.C. 3.4.15.1)","volume":"36","author":"Velletri","year":"1985","journal-title":"Life Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1095\/biolreprod.113.114827","article-title":"Human Sperm Devoid of Germinal Angiotensin-Converting Enzyme is Responsible for Total Fertilization Failure and Lower Fertilization Rates by Conventional in Vitro Fertilization","volume":"90","author":"Li","year":"2014","journal-title":"Biol. Reprod."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"21071","DOI":"10.3390\/ijms141021071","article-title":"Angiotensin-Converting Enzymes Play a Dominant Role in Fertility","volume":"14","author":"Pan","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"5070","DOI":"10.1016\/S0021-9258(18)60680-5","article-title":"Angiotensin II Receptors and Inhibitory Actions in Leydig Cells","volume":"263","author":"Khanum","year":"1988","journal-title":"J. Biol. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/0022-4731(89)90084-8","article-title":"LH Action in the Leydig Cell: Modulation by Angiotensin II and Corticotropin Releasing Hormone, and Regulation of P450(17) Alpha mRNA","volume":"34","author":"Dufau","year":"1989","journal-title":"J. Steroid Biochem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1046\/j.1365-2605.1998.00102.x","article-title":"Pituitary-Dependent Expression of the Testicular Angiotensin II Receptor and its Subtypes in Rats","volume":"21","author":"Hirai","year":"1998","journal-title":"Int. J. Androl."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1984","DOI":"10.1210\/endo-122-5-1984","article-title":"Angiotensin II Receptors in Testes","volume":"122","author":"Millan","year":"1988","journal-title":"Endocrinology"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/1357-4310(95)80018-2","article-title":"The Distribution of Angiotensin II Type 1 Receptors, and the Tissue Renin-Angiotensin Systems","volume":"1","author":"Vinson","year":"1995","journal-title":"Mol. Med. Today"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1111\/j.1365-2605.2007.00771.x","article-title":"In Vivo Administration of Doxazosin in Rats Highly Decreases Serum Circulating Levels of Testosterone through a Mechanism Involving the Testicular Renin-Angiotensin System","volume":"31","year":"2008","journal-title":"Int. J. Androl."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Wang, Z., and Xu, X. (2020). ScRNA-Seq Profiling of Human Testes Reveals the Presence of the ACE2 Receptor, A Target for SARS-CoV-2 Infection in Spermatogonia, Leydig and Sertoli Cells. Cells, 9.","DOI":"10.20944\/preprints202002.0299.v1"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"E1","DOI":"10.1161\/01.RES.87.5.e1","article-title":"A Novel Angiotensin-Converting Enzyme-Related Carboxypeptidase (ACE2) Converts Angiotensin I to Angiotensin 1\u20139","volume":"87","author":"Donoghue","year":"2000","journal-title":"Circ. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1177\/002215540205000510","article-title":"Cell Type-Specific Expression of the Mas Proto-Oncogene in Testis","volume":"50","author":"Alenina","year":"2002","journal-title":"J. Histochem. Cytochem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1038\/nature00786","article-title":"Angiotensin-Converting Enzyme 2 is an Essential Regulator of Heart Function","volume":"417","author":"Crackower","year":"2002","journal-title":"Nature"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1111\/j.1469-7580.2009.01058.x","article-title":"The Role of Angiotensin-(1\u20137) Receptor Mas in Spermatogenesis in Mice and Rats","volume":"214","author":"Leal","year":"2009","journal-title":"J. Anat."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.regpep.2006.11.017","article-title":"Alterations in Gene Expression in the Testis of Angiotensin-(1\u20137)-Receptor Mas-Deficient Mice","volume":"138","author":"Xu","year":"2007","journal-title":"Regul. Pept."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"11867","DOI":"10.1074\/jbc.273.19.11867","article-title":"Sustained Long-Term Potentiation and Anxiety in Mice Lacking the Mas Protooncogene","volume":"273","author":"Walther","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_66","first-page":"437","article-title":"Neutral Metalloendopeptidase in Human Male Genital Tract. Comparison to Angiotensin I-Converting Enzyme","volume":"52","author":"Erdos","year":"1985","journal-title":"Lab. Investig. J. Tech. Methods Pathol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1111\/j.1439-0272.1998.tb01160.x","article-title":"Possible Involvement of Proteases in the Regulation of Spermatogenesis","volume":"30","author":"Monsees","year":"1998","journal-title":"Andrologia"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"4428","DOI":"10.1128\/MCB.24.10.4428-4437.2004","article-title":"Reduced Fertility in Male Mice Deficient in the Zinc Metallopeptidase NL1","volume":"24","author":"Carpentier","year":"2004","journal-title":"Mol. Cell. Biol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1042\/bj3470419","article-title":"Molecular Cloning and Biochemical Characterization of a New Mouse Testis Soluble-Zinc-Metallopeptidase of the Neprilysin Family","volume":"347","author":"Ghaddar","year":"2000","journal-title":"Biochem. J."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1089\/104454901316976127","article-title":"Molecular Cloning, Tissue Distribution, and Chromosomal Localization of MMEL2, a Gene Coding for a Novel Human Member of the Neutral Endopeptidase-24.11 Family","volume":"20","author":"Bonvouloir","year":"2001","journal-title":"DNA Cell Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1186\/1477-7827-8-104","article-title":"Autocrine Regulation of Human Sperm Motility by Tachykinins","volume":"8","author":"Pinto","year":"2010","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1093\/oxfordjournals.jbchem.a021823","article-title":"Alanyl Aminopeptidase from Human Seminal Plasma: Purification, Characterization, and Immunohistochemical Localization in the Male Genital Tract","volume":"122","author":"Huang","year":"1997","journal-title":"J. Biochem."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1210\/mend.15.6.0643","article-title":"Male Reproductive Defects Caused by Puromycin-Sensitive Aminopeptidase Deficiency in Mice","volume":"15","author":"Osada","year":"2001","journal-title":"Mol. Endocrinol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.ygcen.2011.04.015","article-title":"Diet-Induced Hypercholesterolemia Impaired Testicular Steroidogenesis in Mice through the Renin-Angiotensin System","volume":"173","author":"Arrazola","year":"2011","journal-title":"Gen. Comp. Endocrinol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1210\/jcem-66-5-974","article-title":"Prorenin Secretion from Human Testis: No Evidence for Secretion of Active Renin or Angiotensinogen","volume":"66","author":"Sealey","year":"1988","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/0303-7207(95)03505-2","article-title":"Human Seminal Fluid Contains Significant Quantities of Prorenin: Its Correlation with the Sperm Density","volume":"109","author":"Mukhopadhyay","year":"1995","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"3446","DOI":"10.1007\/s00018-008-8230-z","article-title":"Control of Sperm Motility and Fertility: Diverse Factors and Common Mechanisms","volume":"65","author":"Yoshida","year":"2008","journal-title":"Cell Mol. Life Sci."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"63","DOI":"10.3109\/01485018109009377","article-title":"Active and Inactive Renin in Human Seminal Plasma","volume":"7","author":"Craven","year":"1981","journal-title":"Arch. Androl."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/S0015-0282(16)47614-4","article-title":"Angiotensin I Converting Enzyme in the Ejaculate of Fertile and Infertile Men","volume":"41","author":"Hohlbrugger","year":"1984","journal-title":"Fertil. Steril."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1095\/biolreprod62.2.457","article-title":"Genetic Control of Fertility and Embryonic Waste in the Mouse: A Rolefor Angiotensinogen","volume":"62","author":"Tempfer","year":"2000","journal-title":"Biol. Reprod."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1095\/biolreprod33.4.870","article-title":"Localization of the Antigotensin-Converting Enzyme Activity in Testis and Epididymis","volume":"33","author":"Mather","year":"1985","journal-title":"Biol. Reprod."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1007\/BF02118626","article-title":"Gametes Contain Angiotensin Converting Enzyme (Kininase II)","volume":"42","author":"Brentjens","year":"1986","journal-title":"Experientia"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1002\/(SICI)1098-2795(199710)48:2<251::AID-MRD13>3.0.CO;2-0","article-title":"Isolation and Characterization of a Protein with Homology to Angiotensin Converting Enzyme from the Periacrosomal Plasma Membrane of Equine Spermatozoa","volume":"48","author":"Dobrinski","year":"1997","journal-title":"Mol. Reprod. Dev."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/0149-7634(94)00056-7","article-title":"Reproduction and the Renin-Angiotensin System","volume":"19","author":"Ganong","year":"1995","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1093\/humrep\/13.3.604","article-title":"Ultrastructural Localization of Angiotensin-Converting Enzyme in Ejaculated Human Spermatozoa","volume":"13","author":"Kohn","year":"1998","journal-title":"Hum. Reprod."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1111\/j.1439-0272.1985.tb01044.x","article-title":"Angiotensin Converting Enzyme in Semen and its Possible Role in Capacitation","volume":"17","author":"Singh","year":"1985","journal-title":"Andrologia"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1016\/S0015-0282(16)59236-X","article-title":"Angiotensin-Converting Enzyme Content of Human Spermatozoa and its Release during Capacitation","volume":"47","author":"Foresta","year":"1987","journal-title":"Fertil. Steril."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1111\/j.1365-2605.1991.tb01101.x","article-title":"Evidence for the Involvement of Sperm Angiotensin Converting Enzyme in Fertilization","volume":"14","author":"Foresta","year":"1991","journal-title":"Int. J. Androl."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1002\/j.1939-4640.1995.tb00522.x","article-title":"Release of Angiotensin-Converting Enzyme (ACE) from Human Spermatozoa during Capacitation and Acrosome Reaction","volume":"16","author":"Kohn","year":"1995","journal-title":"J. Androl."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1046\/j.1365-2605.2001.00301.x","article-title":"Activity of Testis Angiotensin Converting Enzyme (ACE) in Ejaculated Human Spermatozoa","volume":"24","author":"Shibahara","year":"2001","journal-title":"Int. J. Androl."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1111\/j.1439-0272.1991.tb02533.x","article-title":"Angiotensin-Converting Enzyme and Other Peptidolytic Enzymes in Human Semen and Relations to its Spermatologic Parameters","volume":"23","author":"Siems","year":"1991","journal-title":"Andrologia"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1095\/biolreprod.106.052977","article-title":"Aberrant Distribution of ADAM3 in Sperm from both Angiotensin-Converting Enzyme (Ace)\u2014and Calmegin (Clgn)-Deficient Mice","volume":"75","author":"Yamaguchi","year":"2006","journal-title":"Biol. Reprod."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"498","DOI":"10.4103\/aja.aja_25_18","article-title":"Human Sperm Testicular Angiotensin-Converting Enzyme Helps Determine Human Embryo Quality","volume":"20","author":"Gianzo","year":"2018","journal-title":"Asian J. Androl."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1038\/375146a0","article-title":"Male-Female Differences in Fertility and Blood Pressure in ACE-Deficient Mice","volume":"375","author":"Krege","year":"1995","journal-title":"Nature"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"2552","DOI":"10.1073\/pnas.95.5.2552","article-title":"Angiotensin-Converting Enzyme and Male Fertility","volume":"95","author":"Hagaman","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Inoue, N., Kasahara, T., Ikawa, M., and Okabe, M. (2010). Identification and Disruption of Sperm-Specific Angiotensin Converting Enzyme-3 (ACE3) in Mouse. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0010301"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/S0167-0115(96)00118-8","article-title":"Angiotensin II Stimulates Sperm Motility","volume":"67","author":"Vinson","year":"1996","journal-title":"Regul. Pept."},{"key":"ref_98","first-page":"323","article-title":"Distribution and Function of Angiotensin II Receptors in Mouse Spermatozoa","volume":"31","author":"Wennemuth","year":"1999","journal-title":"Andrologia"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1530\/reprod\/120.1.135","article-title":"Effects of Angiotensin II on the Acrosome Reaction in Equine Spermatozoa","volume":"120","author":"Sabeur","year":"2000","journal-title":"J. Reprod. Fertil."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1677\/joe.0.1440369","article-title":"Type 1 Angiotensin II Receptors in Rat and Human Sperm","volume":"144","author":"Vinson","year":"1995","journal-title":"J. Endocrinol."},{"key":"ref_101","first-page":"E87","article-title":"Angiotensin II Induces Acrosomal Exocytosis in Bovine Spermatozoa","volume":"275","author":"Gur","year":"1998","journal-title":"Am. J. Physiol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1530\/REP-19-0274","article-title":"Role of Angiotensin-(1\u20137) Via MAS Receptor in Human Sperm Motility and Acrosome Reaction","volume":"159","author":"Valdivia","year":"2020","journal-title":"Reproduction"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1016\/j.fertnstert.2007.06.056","article-title":"Expression of Enkephalin-Degrading Enzymes in Human Semen and Implications for Sperm Motility","volume":"89","author":"Subiran","year":"2008","journal-title":"Fertil. Steril."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1006\/dbio.1996.8483","article-title":"Aminopeptidase-Like Protease Released from Oocytes Affects Oocyte Surfaces and Suppresses the Acrosome Reaction in Establishment of Polyspermy Block in Oocytes of the Mussel Mytilus Edulis","volume":"182","author":"Togo","year":"1997","journal-title":"Dev. Biol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1002\/mrd.20037","article-title":"GPI-Anchored Aminopeptidase is Involved in the Acrosome Reaction in Sperm of the Mussel Mytilusedulis","volume":"67","author":"Togo","year":"2004","journal-title":"Mol. Reprod. Dev."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Khatun, A., Rahman, M.S., Ryu, D.Y., Kwon, W.S., and Pang, M.G. (2017). Elevated Aminopeptidase N Affects Sperm Motility and Early Embryo Development. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0184294"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.theriogenology.2018.06.005","article-title":"Effect of Aminopeptidase N on Functions and Fertility of Mouse Spermatozoa in Vitro","volume":"118","author":"Khatun","year":"2018","journal-title":"Theriogenology"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/21\/7943\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:28:33Z","timestamp":1760178513000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/21\/7943"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,26]]},"references-count":107,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2020,11]]}},"alternative-id":["ijms21217943"],"URL":"https:\/\/doi.org\/10.3390\/ijms21217943","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,26]]}}}