Abstract
Purpose
The objective of this study was to analyse the expression and cellular localization of FOXO3, pFOXO3 and PTEN throughout human ovary development both before and after birth.
Methods
Foetal, pubertal and adult paraffin-embedded ovarian samples were analysed by immunohistochemistry for cellular localization of FOXO3, pFOXO3 and PTEN proteins. Protein and mRNA expression were analysed by western blot and real time PCR, respectively, from fresh biopsies.
Results
PTEN was not detected by immunohistochemistry in germ cells and follicles of foetal, pubertal and adult ovaries. Occasional PTEN immunoreactive granulosa cells were found in atretic antral follicles in the adult ovary. Western blot analysis showed low levels of PTEN protein. Nuclear FOXO3-expressing primordial follicles represented a variable proportion of the ovarian reserve. The presence of FOXO3-expressing primordial follicles was very low in foetal ovary; although always represented in a low proportion, prevalence increased during pubertal and adult life.
Conclusion
Our results seem to indicate that two subpopulations of primordial follicles, i.e. nuclear FOXO3-expressing and no FOXO3-expressing primordial follicles are found in the postnatal human ovary. This scenario suggests that FOXO3 could be acting as in the mouse model, preventing primordial follicle activation. However, the strategy would not be an “all or nothing” system as in mouse ovary but rather a selected subpopulation of primordial follicles preserved to ensure long-term fertility.
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Acknowledgements
The authors would like to thank Ms. María Sol Clausi-Schettini for histology technical assistance, and the participating hospitals and patients who contributed samples to this study.
Funding source
This work was supported by intramural grant from Fundación Científica Felipe Fiorellino-Universidad Maimónides, Buenos Aires, Argentina.
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All procedures in the study carried out with human samples were approved by the Institutional Research Ethics Committee from Universidad Maimónides and collaborating Hospitals Research Ethics Board.
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Albamonte, M.I., Calabró, L.Y., Albamonte, M.S. et al. PTEN and FOXO3 expression in the prenatal and postnatal human ovary. J Assist Reprod Genet 37, 1613–1622 (2020). https://doi.org/10.1007/s10815-020-01790-x
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DOI: https://doi.org/10.1007/s10815-020-01790-x