María Itatí Albamonte1, Lara Y Calabró1, Mirta S Albamonte1, Luis Zuccardi2, Inés Stella1,3, Julia Halperin1, Alfredo Daniel Vitullo4. 1. Centro de Estudios Biomédicos Básicos, Aplicados y Desarrollo -CEBBAD, Universidad Maimónides, C1405BCK, Buenos Aires, Argentina. 2. Servicio de Ginecología Infantil, Hospital de Niños "Dr. Ricardo Gutiérrez", C1425EFD, Buenos Aires, Argentina. 3. Servicio de Anatomía Patológica, Hospital Rivadavia, C1425ASQ, Buenos Aires, Argentina. 4. Centro de Estudios Biomédicos Básicos, Aplicados y Desarrollo -CEBBAD, Universidad Maimónides, C1405BCK, Buenos Aires, Argentina. vitullo.alfredo@maimonides.edu.
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.
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.
Entities:
Keywords:
FOXO3; Foetal human ovary; PTEN; Primordial follicle activation; Pubertal and adult human ovary; pFOXO3
Authors: Zhilin Liu; Yi A Ren; Stephanie A Pangas; Jaye Adams; Wei Zhou; Diego H Castrillon; Dagmar Wilhelm; JoAnne S Richards Journal: Mol Endocrinol Date: 2015-06-10
Authors: Pradeep Reddy; Lijun Shen; Chong Ren; Karin Boman; Eva Lundin; Ulrika Ottander; Peter Lindgren; Yi-Xun Liu; Qing-Yuan Sun; Kui Liu Journal: Dev Biol Date: 2005-05-15 Impact factor: 3.582