{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T01:02:33Z","timestamp":1784854953836,"version":"3.55.0"},"reference-count":54,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["222049\/Z\/20\/Z"],"award-info":[{"award-number":["222049\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015652","name":"Barts Charity","doi-asserted-by":"publisher","award":["MGU0552"],"award-info":[{"award-number":["MGU0552"]}],"id":[{"id":"10.13039\/100015652","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014669","name":"British Society for Neuroendocrinology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014669","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000382","name":"Society for Endocrinology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000382","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Neuroendocrinology"],"published-print":{"date-parts":[[2026,7]]},"abstract":"Abstract<\/jats:title>\n \n Mutations in the\n \n MECP2<\/jats:italic>\n <\/jats:styled-content>\n gene, encoding the epigenetic reader Methyl\u2010\n CpG<\/jats:styled-content>\n binding protein 2, are the main cause of Rett syndrome, a rare neurodevelopmental disorder. Besides severe symptoms such as profound intellectual disability, loss of speech and motor skills, and epilepsy, loss of function of\n \n MECP2<\/jats:italic>\n <\/jats:styled-content>\n has been associated with pubertal dysregulation, but the biological mechanisms leading to this remain unclear. Using a mouse model of Rett, in which males are hemizygous and females heterozygous for\n Mecp2<\/jats:italic>\n loss of function mutation, we assessed the onset and progression of puberty, together with increase in body weight and onset of neurological symptoms in post\u2010weaning mice until puberty. In brain samples of young adult mice, we analysed hypothalamic Gonadotropin releasing hormone (\n GnRH<\/jats:styled-content>\n ) neurons by immunofluorescent labelling, and in plasma samples we measured circulating\n GnRH<\/jats:styled-content>\n ,\n LH<\/jats:styled-content>\n , and testosterone concentrations. Finally, we analysed testosterone\u2010dependent arginine\u2010vasopressin circuits. In our mouse model we found delayed puberty in\n Mecp2<\/jats:italic>\n \n \n CD1<\/jats:italic>\n <\/jats:sup>\n <\/jats:styled-content>\n \u2010null males, associated with a reduced rate of weight gain, but with puberty onset occurring at a lower body weight than in wildtype controls. Despite later puberty onset,\n \n Mecp2<\/jats:italic>\n \n CD1<\/jats:italic>\n <\/jats:sup>\n <\/jats:styled-content>\n \u2010null male mice were found to have an increased number of\n GnRH<\/jats:styled-content>\n neurons, but displayed lower levels of circulating reproductive hormones. Consequently,\n \n Mecp2<\/jats:italic>\n \n CD1<\/jats:italic>\n <\/jats:sup>\n <\/jats:styled-content>\n \u2010null males have deficient testosterone\u2010dependent arginine\u2010vasopressin innervation. In female\n \n Mecp2<\/jats:italic>\n \n CD1<\/jats:italic>\n <\/jats:sup>\n <\/jats:styled-content>\n \u2010heterozygous mice, we found no overall significant differences in pubertal development or\n GnRH<\/jats:styled-content>\n neurons. The lack of significant alterations in females might be related to a later onset of neurological symptoms due to heterozygosity. Our data supports that\n \n MECP2<\/jats:italic>\n <\/jats:styled-content>\n is essential for typical pubertal development, with complete loss of\n Mecp2<\/jats:italic>\n in a male murine model resulting in abnormalities of pubertal timing related to lower body weight, with an observed increase in hypothalamic\n GnRH<\/jats:styled-content>\n neurons.\n <\/jats:p>","DOI":"10.1111\/jne.70221","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T23:38:56Z","timestamp":1782430736000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pubertal development and hypothalamic\u2013pituitary\u2013gonadal axis are altered in male mice lacking\n Mecp2<\/i>"],"prefix":"10.1111","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7046-8886","authenticated-orcid":false,"given":"Ana","family":"Mart\u00edn\u2010S\u00e1nchez","sequence":"first","affiliation":[{"name":"Department of Cell Biology and Functional Biology, Faculty of Biological Sciences Universitat de Val\u00e8ncia Val\u00e8ncia Spain"},{"name":"Unitat Predepartamental de Medicina Universitat Jaume I de Castell\u00f3 Castell\u00f3 de la Plana Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2811-6134","authenticated-orcid":false,"given":"Daniela","family":"Jim\u00e9nez\u2010D\u00edaz","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Functional Biology, Faculty of Biological Sciences Universitat de Val\u00e8ncia Val\u00e8ncia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6462-1604","authenticated-orcid":false,"given":"Rafael","family":"Esteve\u2010P\u00e9rez","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Functional Biology, Faculty of Biological Sciences Universitat de Val\u00e8ncia Val\u00e8ncia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandru","family":"Vasile\u2010Tudorache","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Functional Biology, Faculty of Biological Sciences Universitat de Val\u00e8ncia Val\u00e8ncia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6731-4440","authenticated-orcid":false,"given":"Jordan E.","family":"Read","sequence":"additional","affiliation":[{"name":"Centre for Endocrinology, William Harvey Research Institute Queen Mary University of London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6698-903X","authenticated-orcid":false,"given":"Sasha R.","family":"Howard","sequence":"additional","affiliation":[{"name":"Centre for Endocrinology, William Harvey Research Institute Queen Mary University of London London UK"},{"name":"Department of Paediatric Endocrinology Royal London 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