PMID- 35248053
OWN - NLM
STAT- MEDLINE
DCOM- 20220322
LR  - 20220722
IS  - 1477-7827 (Electronic)
IS  - 1477-7827 (Linking)
VI  - 20
IP  - 1
DP  - 2022 Mar 5
TI  - Activation of AKT/mammalian target of rapamycin signaling in the peripheral blood 
      of women with premature ovarian insufficiency and its correlation with FMR1 
      expression.
PG  - 44
LID - 10.1186/s12958-022-00919-0 [doi]
LID - 44
AB  - 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.
CI  - (c) 2022. The Author(s).
FAU - Rehnitz, Julia
AU  - Rehnitz J
AUID- ORCID: 0000-0003-4409-4697
AD  - University Women's Hospital Heidelberg, Department of Gynecological Endocrinology 
      and Fertility Disorders, Heidelberg, Germany. 
      Julia.Rehnitz@med.uni-heidelberg.de.
FAU - Messmer, Birgitta
AU  - Messmer B
AD  - University Women's Hospital Heidelberg, Department of Gynecological Endocrinology 
      and Fertility Disorders, Heidelberg, Germany.
FAU - Bender, Ulrike
AU  - Bender U
AD  - University Women's Hospital Heidelberg, Department of Gynecological Endocrinology 
      and Fertility Disorders, Heidelberg, Germany.
FAU - Nguyen, Xuan Phuoc
AU  - Nguyen XP
AD  - University Women's Hospital Heidelberg, Department of Gynecological Endocrinology 
      and Fertility Disorders, Heidelberg, Germany.
FAU - Germeyer, Ariane
AU  - Germeyer A
AD  - University Women's Hospital Heidelberg, Department of Gynecological Endocrinology 
      and Fertility Disorders, Heidelberg, Germany.
FAU - Hinderhofer, Katrin
AU  - Hinderhofer K
AD  - Institute of Human Genetics, University Heidelberg, Laboratory of Molecular 
      Genetics, Heidelberg, Germany.
FAU - Strowitzki, Thomas
AU  - Strowitzki T
AD  - University Women's Hospital Heidelberg, Department of Gynecological Endocrinology 
      and Fertility Disorders, Heidelberg, Germany.
FAU - Capp, Edison
AU  - Capp E
AD  - University Women's Hospital Heidelberg, Department of Gynecological Endocrinology 
      and Fertility Disorders, Heidelberg, Germany.
AD  - Department of Obstetrics and Gynecology, Medicine School, Universidade Federal Do 
      Rio Grande Do Sul, Porto Alegre, Brazil.
LA  - eng
GR  - RE 3647-1-2 to JR/Deutsche Forschungsgemeinschaft/
GR  - scholarship/Conselho Nacional de Desenvolvimento Cientifico e Tecnologico/
PT  - Journal Article
PT  - Observational Study
DEP - 20220305
PL  - England
TA  - Reprod Biol Endocrinol
JT  - Reproductive biology and endocrinology : RB&E
JID - 101153627
RN  - 0 (FMR1 protein, human)
RN  - 139135-51-6 (Fragile X Mental Retardation Protein)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (AKT1 protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Adult
MH  - Case-Control Studies
MH  - Female
MH  - Fragile X Mental Retardation Protein/*genetics/metabolism
MH  - Gene Expression Regulation
MH  - Humans
MH  - Ovarian Reserve/genetics
MH  - *Primary Ovarian Insufficiency/blood/genetics
MH  - *Proto-Oncogene Proteins c-akt/blood/genetics
MH  - Signal Transduction/physiology
MH  - *TOR Serine-Threonine Kinases/blood/genetics
MH  - Up-Regulation/physiology
PMC - PMC8898473
OTO - NOTNLM
OT  - AKT
OT  - Fragile X mental retardation 1 gene
OT  - Mammalian target of rapamycin
OT  - Premature ovarian insufficiency
OT  - S6 kinase
OT  - Tuberous sclerosis complex 2
COIS- The authors declare no conflicts of interest.
EDAT- 2022/03/07 06:00
MHDA- 2022/03/23 06:00
PMCR- 2022/03/05
CRDT- 2022/03/06 20:24
PHST- 2021/11/14 00:00 [received]
PHST- 2022/02/27 00:00 [accepted]
PHST- 2022/03/06 20:24 [entrez]
PHST- 2022/03/07 06:00 [pubmed]
PHST- 2022/03/23 06:00 [medline]
PHST- 2022/03/05 00:00 [pmc-release]
AID - 10.1186/s12958-022-00919-0 [pii]
AID - 919 [pii]
AID - 10.1186/s12958-022-00919-0 [doi]
PST - epublish
SO  - Reprod Biol Endocrinol. 2022 Mar 5;20(1):44. doi: 10.1186/s12958-022-00919-0.