{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T01:22:40Z","timestamp":1791336160846,"version":"4.3.1"},"reference-count":245,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2021,8,30]],"date-time":"2021-08-30T00:00:00Z","timestamp":1630281600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["GR-2016-02362389"],"award-info":[{"award-number":["GR-2016-02362389"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Gonadotropin releasing hormone (GnRH) neurons are hypothalamic neuroendocrine cells that control sexual reproduction. During embryonic development, GnRH neurons migrate from the nose to the hypothalamus, where they receive inputs from several afferent neurons, following the axonal scaffold patterned by nasal nerves. Each step of GnRH neuron development depends on the orchestrated action of several molecules exerting specific biological functions. Mutations in genes encoding for these essential molecules may cause Congenital Hypogonadotropic Hypogonadism (CHH), a rare disorder characterized by GnRH deficiency, delayed puberty and infertility. Depending on their action in the GnRH neuronal system, CHH causative genes can be divided into neurodevelopmental and neuroendocrine genes. The CHH genetic complexity, combined with multiple inheritance patterns, results in an extreme phenotypic variability of CHH patients. In this review, we aim at providing a comprehensive and updated description of the genes thus far associated with CHH, by dissecting their biological relevance in the GnRH system and their functional relevance underlying CHH pathogenesis.<\/jats:p>","DOI":"10.3390\/ijms22179425","type":"journal-article","created":{"date-parts":[[2021,8,30]],"date-time":"2021-08-30T11:01:37Z","timestamp":1630321297000},"page":"9425","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["The Differential Roles for Neurodevelopmental and Neuroendocrine Genes in Shaping GnRH Neuron Physiology and Deficiency"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5692-3328","authenticated-orcid":false,"given":"Roberto","family":"Oleari","sequence":"first","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences, University of Milan, 20133 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2246-9515","authenticated-orcid":false,"given":"Valentina","family":"Massa","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University of Milan, 20142 Milano, Italy"},{"name":"CRC Aldo Ravelli for Neurotechnology and Experimental Brain Therapeutics, Department of Health Sciences, University of Milan, 20142 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8630-8361","authenticated-orcid":false,"given":"Anna","family":"Cariboni","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences, University of Milan, 20133 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7750-0423","authenticated-orcid":false,"given":"Antonella","family":"Lettieri","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University of Milan, 20142 Milano, Italy"},{"name":"CRC Aldo Ravelli for Neurotechnology and Experimental Brain Therapeutics, Department of Health Sciences, University of Milan, 20142 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.metabol.2017.11.018","article-title":"The hypothalamus-pituitary-gonad axis: Tales of mice and men","volume":"86","author":"Kaprara","year":"2018","journal-title":"Metabolism"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1038\/nrendo.2015.112","article-title":"Expert consensus document: European Consensus Statement on congenital hypogonadotropic hypogonadism\u2014pathogenesis, diagnosis and treatment","volume":"11","author":"Boehm","year":"2015","journal-title":"Nat. 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