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Reduced Foxo3a, FoxL2, and p27 mRNA expression in human ovarian tissue in premature ovarian insufficiency

  • Nikolaos ThanatsisEmail author
  • Apostolos Kaponis
  • Vasiliki Koika
  • Neoklis A. Georgopoulos
  • George O. Decavalas
Original Article



Previous studies have suggested that deletion of Foxo3a, FoxL2, PTEN, p27, and AMH leads to early exhaustion of the primordial follicle pool and premature ovarian insufficiency (POI) in transgenic mice. Our aim was to assess for the first time, to our knowledge, messenger RNA (mRNA) expression of these genes and AMHR2 in human ovarian tissue from women with POI. We hypothesized that these genes would be underexpressed in POI women compared with healthy controls.


mRNA levels were evaluated by quantitative reverse transcription-polymerase chain reaction and real-time polymerase chain reaction in cortical ovarian tissue obtained by laparoscopy from Caucasian Greek women with POI (n = 5) and healthy women with normal menstruation (n = 6). Morphological analysis of the ovarian biopsies was also performed to assess the presence of primordial or other types of growing follicles.


Ovarian tissue from POI patients showed lower Foxo3a, FoxL2, and p27 mRNA expression compared with controls (p = 0.017, p = 0.017, and p = 0.030, respectively). mRNA expression of AMH, PTEN, and AMHR2 was reduced in ovarian biopsies from POI patients as well. However, these differences were not statistically significant (p = 0.143, p = 0.247, and p = 0.662, respectively). Morphological analysis showed complete lack of follicular structures in all POI biopsies.


Our findings suggest a possible role of Foxo3a, FoxL2, and p27 in the pathogenesis of human POI, which may prove to be of great diagnostic-therapeutic value. Further larger studies are needed to identify a similar pattern for AMH, PTEN, and AMHR2 and to investigate gene expression at a protein level.


Premature ovarian insufficiency Primordial follicles Foxo3a FoxL2 AMH 


Funding information

This work was supported by research grants from the Basic Research Program “Κ. Κaratheodori” 2013 of the Research Committee of the University of Patras, Greece (grant number E050).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee (Institutional Ethics Research Committee and Scientific Board of Patras University Hospital) and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.


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Copyright information

© Hellenic Endocrine Society 2019

Authors and Affiliations

  1. 1.Department of Obstetrics and GynecologyPatras University School of MedicinePatrasGreece
  2. 2.Division of Reproductive Endocrinology, Department of Obstetrics & GynecologyPatras University School of MedicinePatrasGreece

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