Activation of AKT/mammalian target of rapamycin signaling in the peripheral blood of women with premature ovarian insufficiency and its correlation with FMR1 expression

Detalhes bibliográficos
Autor(a) principal: Rehnitz, Julia
Data de Publicação: 2022
Outros Autores: Messmer, Birgitta, Bender, Ulrike, Xuan, Phuoc Nguyen, Germeyer, Ariane, Hinderhofer, Katrin, Strowitzki, Thomas, Capp, Edison
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UFRGS
Texto Completo: http://hdl.handle.net/10183/237099
Resumo: Background: The protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway regulates early follicular activation and follicular pool maintenance in female germline cells. Fragile X mental retardation 1 (FMR1) regulates folliculogenesis and it is variably expressed in patients with Premature Ovary Insufficiency. FMR1 expression is supposed to be linked to AKT/mTOR signaling in an ovarian response dependent manner as demonstrated in recent in vitro and in vivo studies in the female germline in vitro and in vivo. Methods: 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 FMR1 expression. Results: Expression of the genes AKT1, TSC2, mTOR, and S6K was significantly more abundant in patients with POI than in the controls. For AKT1, TSC2 and mTOR, gene expression was not affected by FMR1-CGG repeat number in the 5´-untranslated region. FMR1 and S6K expression levels, however, were significantly upregulated in patients with POI and an FMR1 premutation. Independent of a premutation, expression of mTOR, S6K, and TSC2 was significantly correlated with that of FMR1 in all patients. Furthermore, when grouped according to ovarian reserve, this effect remained significant only for mTOR and S6K, with higher significance note in patients with Premature Ovarian Insufficiency than in the controls. Conclusions: In Premature ovarian insufficiency patients, activation of AKT/mTOR signaling pathway is remarkable and putatively pathognomonic. Additionally, it seems to be triggered by an FMR1/mTOR/S6K linkage mechanism, most relevant in premutation carriers.
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spelling Rehnitz, JuliaMessmer, BirgittaBender, UlrikeXuan, Phuoc NguyenGermeyer, ArianeHinderhofer, KatrinStrowitzki, ThomasCapp, Edison2022-04-13T04:50:54Z20221477-7827http://hdl.handle.net/10183/237099001138438Background: The protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway regulates early follicular activation and follicular pool maintenance in female germline cells. Fragile X mental retardation 1 (FMR1) regulates folliculogenesis and it is variably expressed in patients with Premature Ovary Insufficiency. FMR1 expression is supposed to be linked to AKT/mTOR signaling in an ovarian response dependent manner as demonstrated in recent in vitro and in vivo studies in the female germline in vitro and in vivo. Methods: 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 FMR1 expression. Results: Expression of the genes AKT1, TSC2, mTOR, and S6K was significantly more abundant in patients with POI than in the controls. For AKT1, TSC2 and mTOR, gene expression was not affected by FMR1-CGG repeat number in the 5´-untranslated region. FMR1 and S6K expression levels, however, were significantly upregulated in patients with POI and an FMR1 premutation. Independent of a premutation, expression of mTOR, S6K, and TSC2 was significantly correlated with that of FMR1 in all patients. Furthermore, when grouped according to ovarian reserve, this effect remained significant only for mTOR and S6K, with higher significance note in patients with Premature Ovarian Insufficiency than in the controls. Conclusions: In Premature ovarian insufficiency patients, activation of AKT/mTOR signaling pathway is remarkable and putatively pathognomonic. Additionally, it seems to be triggered by an FMR1/mTOR/S6K linkage mechanism, most relevant in premutation carriers.application/pdfengReproductive biology and endocrinology. London. Vol. 20 (2022), 44, 7 p.Proteínas proto-oncogênicas c-aktDeficiência intelectualInsuficiência ovariana primáriaProteína 2 do complexo esclerose tuberosaAKTFragile X mental retardation 1 geneMammalian target of rapamycinPremature ovarian insufficiencyS6 kinaseTuberous sclerosis complex 2Activation of AKT/mammalian target of rapamycin signaling in the peripheral blood of women with premature ovarian insufficiency and its correlation with FMR1 expressionEstrangeiroinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFRGSinstname:Universidade Federal do Rio Grande do Sul (UFRGS)instacron:UFRGSTEXT001138438.pdf.txt001138438.pdf.txtExtracted Texttext/plain33472http://www.lume.ufrgs.br/bitstream/10183/237099/2/001138438.pdf.txt90886a556922c16607e371be591620dcMD52ORIGINAL001138438.pdfTexto completo (inglês)application/pdf951556http://www.lume.ufrgs.br/bitstream/10183/237099/1/001138438.pdf0d5573b131e3cd076823f2a717733879MD5110183/2370992022-04-20 04:48:23.577547oai:www.lume.ufrgs.br:10183/237099Repositório de PublicaçõesPUBhttps://lume.ufrgs.br/oai/requestopendoar:2022-04-20T07:48:23Repositório Institucional da UFRGS - Universidade Federal do Rio Grande do Sul (UFRGS)false
dc.title.pt_BR.fl_str_mv Activation of AKT/mammalian target of rapamycin signaling in the peripheral blood of women with premature ovarian insufficiency and its correlation with FMR1 expression
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
spellingShingle Activation of AKT/mammalian target of rapamycin signaling in the peripheral blood of women with premature ovarian insufficiency and its correlation with FMR1 expression
Rehnitz, Julia
Proteínas proto-oncogênicas c-akt
Deficiência intelectual
Insuficiência ovariana primária
Proteína 2 do complexo esclerose tuberosa
AKT
Fragile X mental retardation 1 gene
Mammalian target of rapamycin
Premature ovarian insufficiency
S6 kinase
Tuberous sclerosis complex 2
title_short Activation of AKT/mammalian target of rapamycin signaling in the peripheral blood of women with premature ovarian insufficiency and its correlation with FMR1 expression
title_full Activation of AKT/mammalian target of rapamycin signaling in the peripheral blood of women with premature ovarian insufficiency and its correlation with FMR1 expression
title_fullStr Activation of AKT/mammalian target of rapamycin signaling in the peripheral blood of women with premature ovarian insufficiency and its correlation with FMR1 expression
title_full_unstemmed Activation of AKT/mammalian target of rapamycin signaling in the peripheral blood of women with premature ovarian insufficiency and its correlation with FMR1 expression
title_sort Activation of AKT/mammalian target of rapamycin signaling in the peripheral blood of women with premature ovarian insufficiency and its correlation with FMR1 expression
author Rehnitz, Julia
author_facet Rehnitz, Julia
Messmer, Birgitta
Bender, Ulrike
Xuan, Phuoc Nguyen
Germeyer, Ariane
Hinderhofer, Katrin
Strowitzki, Thomas
Capp, Edison
author_role author
author2 Messmer, Birgitta
Bender, Ulrike
Xuan, Phuoc Nguyen
Germeyer, Ariane
Hinderhofer, Katrin
Strowitzki, Thomas
Capp, Edison
author2_role author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Rehnitz, Julia
Messmer, Birgitta
Bender, Ulrike
Xuan, Phuoc Nguyen
Germeyer, Ariane
Hinderhofer, Katrin
Strowitzki, Thomas
Capp, Edison
dc.subject.por.fl_str_mv Proteínas proto-oncogênicas c-akt
Deficiência intelectual
Insuficiência ovariana primária
Proteína 2 do complexo esclerose tuberosa
topic Proteínas proto-oncogênicas c-akt
Deficiência intelectual
Insuficiência ovariana primária
Proteína 2 do complexo esclerose tuberosa
AKT
Fragile X mental retardation 1 gene
Mammalian target of rapamycin
Premature ovarian insufficiency
S6 kinase
Tuberous sclerosis complex 2
dc.subject.eng.fl_str_mv AKT
Fragile X mental retardation 1 gene
Mammalian target of rapamycin
Premature ovarian insufficiency
S6 kinase
Tuberous sclerosis complex 2
description Background: The protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway regulates early follicular activation and follicular pool maintenance in female germline cells. Fragile X mental retardation 1 (FMR1) regulates folliculogenesis and it is variably expressed in patients with Premature Ovary Insufficiency. FMR1 expression is supposed to be linked to AKT/mTOR signaling in an ovarian response dependent manner as demonstrated in recent in vitro and in vivo studies in the female germline in vitro and in vivo. Methods: 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 FMR1 expression. Results: Expression of the genes AKT1, TSC2, mTOR, and S6K was significantly more abundant in patients with POI than in the controls. For AKT1, TSC2 and mTOR, gene expression was not affected by FMR1-CGG repeat number in the 5´-untranslated region. FMR1 and S6K expression levels, however, were significantly upregulated in patients with POI and an FMR1 premutation. Independent of a premutation, expression of mTOR, S6K, and TSC2 was significantly correlated with that of FMR1 in all patients. Furthermore, when grouped according to ovarian reserve, this effect remained significant only for mTOR and S6K, with higher significance note in patients with Premature Ovarian Insufficiency than in the controls. Conclusions: In Premature ovarian insufficiency patients, activation of AKT/mTOR signaling pathway is remarkable and putatively pathognomonic. Additionally, it seems to be triggered by an FMR1/mTOR/S6K linkage mechanism, most relevant in premutation carriers.
publishDate 2022
dc.date.accessioned.fl_str_mv 2022-04-13T04:50:54Z
dc.date.issued.fl_str_mv 2022
dc.type.driver.fl_str_mv Estrangeiro
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dc.identifier.issn.pt_BR.fl_str_mv 1477-7827
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dc.language.iso.fl_str_mv eng
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dc.relation.ispartof.pt_BR.fl_str_mv Reproductive biology and endocrinology. London. Vol. 20 (2022), 44, 7 p.
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