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Crosstalk between PTEN/PI3K/Akt Signalling and DNA Damage in the Oocyte: Implications for Primordial Follicle Activation, Oocyte Quality and Ageing

1
MRC Centre for Reproductive Health, Queens Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK
2
Institute of Cell Biology, University of Edinburgh, Edinburgh EH9 3FF, UK
3
Obstetrics and Gynaecology Department, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia
*
Author to whom correspondence should be addressed.
Cells 2020, 9(1), 200; https://doi.org/10.3390/cells9010200
Received: 31 October 2019 / Revised: 6 January 2020 / Accepted: 13 January 2020 / Published: 14 January 2020
(This article belongs to the Special Issue Double-Strand DNA Break Repair and Human Disease)
The preservation of genome integrity in the mammalian female germline from primordial follicle arrest to activation of growth to oocyte maturation is fundamental to ensure reproductive success. As oocytes are formed before birth and may remain dormant for many years, it is essential that defence mechanisms are monitored and well maintained. The phosphatase and tensin homolog of chromosome 10 (PTEN)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB, Akt) is a major signalling pathway governing primordial follicle recruitment and growth. This pathway also contributes to cell growth, survival and metabolism, and to the maintenance of genomic integrity. Accelerated primordial follicle activation through this pathway may result in a compromised DNA damage response (DDR). Additionally, the distinct DDR mechanisms in oocytes may become less efficient with ageing. This review considers DNA damage surveillance mechanisms and their links to the PTEN/PI3K/Akt signalling pathway, impacting on the DDR during growth activation of primordial follicles, and in ovarian ageing. Targeting DDR mechanisms within oocytes may be of value in developing techniques to protect ovaries against chemotherapy and in advancing clinical approaches to regulate primordial follicle activation.
Keywords: PTEN/PI3K/Akt; follicle activation; DNA damage response (DDR); ageing PTEN/PI3K/Akt; follicle activation; DNA damage response (DDR); ageing
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Maidarti, M.; Anderson, R.A.; Telfer, E.E. Crosstalk between PTEN/PI3K/Akt Signalling and DNA Damage in the Oocyte: Implications for Primordial Follicle Activation, Oocyte Quality and Ageing. Cells 2020, 9, 200.

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