{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T13:07:31Z","timestamp":1793020051352,"version":"4.5.0"},"reference-count":112,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,12,22]],"date-time":"2022-12-22T00:00:00Z","timestamp":1671667200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>\n                    The pubertal development onset is controlled by a network of genes that regulate the gonadotropin releasing hormone (GnRH) pulsatile release and the subsequent increase of the circulating levels of pituitary gonadotropins that activate the gonadal function. Although the transition from pre-pubertal condition to puberty occurs physiologically in a delimited age-range, the inception of pubertal development can be anticipated or delayed due to genetic and epigenetic changes or environmental conditions. Most of the genetic and epigenetic alterations concern genes which encode for kisspeptin, GnRH, LH, FSH and their receptor, which represent crucial factors of the hypothalamic-pituitary-gonadal (HPG) axis. Recent data indicate a central role of the epigenome in the regulation of genes in the hypothalamus and pituitary that could mediate the flexibility of pubertal timing. Identification of epigenetically regulated genes, such as Makorin ring finger 3 (\n                    <jats:italic>MKRN3<\/jats:italic>\n                    ) and Delta-like 1 homologue (\n                    <jats:italic>DLK1<\/jats:italic>\n                    ), respectively responsible for the repression and the activation of pubertal development, provides additional evidence of how epigenetic variations affect pubertal timing. This review aims to investigate genetic, epigenetic, and environmental factors responsible for the regulation of precocious and delayed puberty.\n                  <\/jats:p>","DOI":"10.3389\/fendo.2022.1019468","type":"journal-article","created":{"date-parts":[[2022,12,22]],"date-time":"2022-12-22T00:18:26Z","timestamp":1671668306000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":46,"title":["Genetic, epigenetic and enviromental influencing factors on the regulation of precocious and delayed puberty"],"prefix":"10.3389","volume":"13","author":[{"given":"Maria Felicia","family":"Faienza","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavia","family":"Urbano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi Antonio","family":"Moscogiuri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariangela","family":"Chiarito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"De Santis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Giordano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,12,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"101265","DOI":"10.1016\/j.beem.2019.03.001","article-title":"Puberty: normal physiology","volume":"33","author":"Wood","year":"2019","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(15)00418-0","article-title":"Pubertal development and regulation","volume":"4","author":"Abreu","year":"2016","journal-title":"Lancet Diabetes Endocrinol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1111\/ppe.12507","article-title":"Timing of puberty in boys and girls: A population-based study","volume":"33","author":"Brix","year":"2019","journal-title":"Paediatr Perinat Epidemiol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.mce.2010.03.011","article-title":"Trends in puberty timing in humans and environmental modifiers","volume":"324","author":"Toppari","year":"2010","journal-title":"Mol Cell Endocrinol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1007\/s11113-017-9441-5","article-title":"Race disparities in pubertal timing: Implications for cardiovascular disease risk among African American women","volume":"36","author":"Bleil","year":"2017","journal-title":"Popul Res Policy Rev"},{"key":"B6","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1159\/000353759","article-title":"Puberty in children born small for gestational age","volume":"80","author":"Verkauskiene","year":"2013","journal-title":"Horm Res Paediatr"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3390\/nu13020419","article-title":"The role of fetal, infant, and childhood nutrition in the timing of sexual maturation","volume":"13","author":"Calcaterra","year":"2021","journal-title":"Nutrients"},{"key":"B8","doi-asserted-by":"publisher","first-page":"E1269","DOI":"10.3390\/ijerph14101266","article-title":"Association between obesity and puberty timing: A systematic review and meta-analysis","volume":"14","author":"Li","year":"2017","journal-title":"Int J Environ Res Public Health"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2009-2636","article-title":"Role of prenatal characteristics and early growth on pubertal attainment of British girls","volume":"126","author":"Maisonet","year":"2010","journal-title":"Pediatr"},{"key":"B10","doi-asserted-by":"publisher","first-page":"999","DOI":"10.1016\/j.chemosphere.2008.05.053","article-title":"Delayed initiation of breast development in girls with higher prenatal dioxin exposure; 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