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Fragile X mental retardation 1 (<jats:italic>FMR1<\/jats:italic>) regulates folliculogenesis and it is variably expressed in patients with Premature Ovary Insufficiency. <jats:italic>FMR1<\/jats:italic> expression is supposed to be linked to AKT\/mTOR signaling in an ovarian response dependent manner as demonstrated in recent <jats:italic>in<\/jats:italic><jats:italic>vitro<\/jats:italic> and <jats:italic>in<\/jats:italic><jats:italic>vivo<\/jats:italic> studies in the female germline <jats:italic>in<\/jats:italic><jats:italic>vitro<\/jats:italic> and <jats:italic>in<\/jats:italic><jats:italic>vivo<\/jats:italic>.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We evaluated changes in the expression of AKT\/mTOR signaling pathway genes by real time PCR in the peripheral blood of 74 patients with Premature Ovarian Insufficiency and 56 fertile controls and correlated their expression with <jats:italic>FMR1<\/jats:italic> expression.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Expression of the genes <jats:italic>AKT1<\/jats:italic>, <jats:italic>TSC2, mTOR<\/jats:italic>, and <jats:italic>S6K<\/jats:italic> was significantly more abundant in patients with POI than in the controls. For <jats:italic>AKT1<\/jats:italic>, <jats:italic>TSC2<\/jats:italic> and <jats:italic>mTOR,<\/jats:italic> gene expression was not affected by <jats:italic>FMR1<\/jats:italic>-CGG repeat number in the 5\u00b4-untranslated region. <jats:italic>FMR1<\/jats:italic> and <jats:italic>S6K<\/jats:italic> expression levels<jats:italic>,<\/jats:italic> however, were significantly upregulated in patients with POI and an <jats:italic>FMR1<\/jats:italic> premutation. Independent of a premutation, expression of <jats:italic>mTOR<\/jats:italic>, <jats:italic>S6K<\/jats:italic>, and <jats:italic>TSC2<\/jats:italic> was significantly correlated with that of <jats:italic>FMR1<\/jats:italic> in all patients. Furthermore, when grouped according to ovarian reserve, this effect remained significant only for <jats:italic>mTOR<\/jats:italic> and <jats:italic>S6K<\/jats:italic>, with higher significance note in patients with Premature Ovarian Insufficiency than in the controls.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>In Premature ovarian insufficiency patients, activation of AKT\/mTOR signaling pathway is remarkable and putatively pathognomonic. Additionally, it seems to be triggered by an <jats:italic>FMR1<\/jats:italic>\/<jats:italic>mTOR<\/jats:italic>\/<jats:italic>S6K<\/jats:italic> linkage mechanism, most relevant in premutation carriers.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12958-022-00919-0","type":"journal-article","created":{"date-parts":[[2022,3,5]],"date-time":"2022-03-05T13:02:43Z","timestamp":1646485363000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Activation of AKT\/mammalian target of rapamycin signaling in the peripheral blood of women with premature ovarian insufficiency and its correlation with FMR1 expression"],"prefix":"10.1186","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4409-4697","authenticated-orcid":false,"given":"Julia","family":"Rehnitz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgitta","family":"Messmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike","family":"Bender","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan Phuoc","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariane","family":"Germeyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrin","family":"Hinderhofer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Strowitzki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edison","family":"Capp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,3,5]]},"reference":[{"key":"919_CR1","doi-asserted-by":"publisher","first-page":"1397","DOI":"10.2174\/092986706776872943","volume":"13","author":"W Fassnacht","year":"2006","unstructured":"Fassnacht W, Mempel A, Strowitzki T, Vogt PH. 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