Activation of AKT/mammalian target of rapamycin signaling in the peripheral blood of women with premature ovarian insufficiency and its correlation with FMR1 expression
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , , , |
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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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 info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10183/237099 |
dc.identifier.issn.pt_BR.fl_str_mv |
1477-7827 |
dc.identifier.nrb.pt_BR.fl_str_mv |
001138438 |
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1477-7827 001138438 |
url |
http://hdl.handle.net/10183/237099 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartof.pt_BR.fl_str_mv |
Reproductive biology and endocrinology. London. Vol. 20 (2022), 44, 7 p. |
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info:eu-repo/semantics/openAccess |
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openAccess |
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