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Reduced Foxo3a, FoxL2, and p27 mRNA expression in human ovarian tissue in premature ovarian insufficiency
Nikolaos Thanatsis1, Apostolos Kaponis2, Vasiliki Koika3
1Department of Obstetrics and Gynecology, Patras University School of Medicine, 26504, Patras, Greece. nikolaos.thanatsis@nhs.net.
Purpose:
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.
Methods:
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.
Results:
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.
Conclusions:
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.
Insights
Reduced expression of Foxo3a, FoxL2, and p27 genes in ovarian tissue is linked to premature ovarian insufficiency (POI). This finding may aid in diagnosing and treating POI. Further research is needed for other genes.
Area of Science:
- Reproductive Biology
- Genetics
- Endocrinology
Background:
- Premature ovarian insufficiency (POI) is characterized by the depletion of the primordial follicle pool.
- Previous studies in mice suggest gene deletions (Foxo3a, FoxL2, PTEN, p27, AMH) contribute to POI.
- The role of these genes in human POI remains largely uncharacterized.
Purpose of the Study:
- To investigate messenger RNA (mRNA) expression of Foxo3a, FoxL2, PTEN, p27, AMH, and AMHR2 in human ovarian tissue from women with POI.
- To compare gene expression levels between women with POI and healthy controls.
- To explore the potential role of these genes in the pathogenesis of human POI.
Main Methods:
- Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and real-time polymerase chain reaction (qPCR) were used to evaluate mRNA levels.
- Ovarian cortical tissue samples were obtained laparoscopically from Caucasian Greek women diagnosed with POI (n=5) and healthy controls (n=6).
- Morphological analysis of ovarian biopsies was conducted to assess the presence and type of ovarian follicles.
Main Results:
- Significantly lower mRNA expression of Foxo3a, FoxL2, and p27 was observed in ovarian tissue from POI patients compared to controls (p<0.05).
- Reduced mRNA levels of AMH, PTEN, and AMHR2 were also noted in POI patients, but these differences did not reach statistical significance.
- All POI biopsies exhibited a complete absence of primordial or growing follicular structures.
Conclusions:
- The findings suggest a potential role for Foxo3a, FoxL2, and p27 in the development of human POI.
- These genes may hold diagnostic and therapeutic significance for POI.
- Larger studies are warranted to confirm findings for AMH, PTEN, and AMHR2 and to investigate gene expression at the protein level.
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