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

Abstract

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.

Human umbilical cord mesenchymal stem cells restore the ovarian metabolome and rescue premature ovarian insufficiency in mice

“…As reported by Maidarti and colleagues, the PI3K/Akt pathway is critical for ovarian development, follicular growth, and the proliferation and differentiation of granulosa cells [ 46 ]. Sphingosine (such as S1P, Fig.…”

Primordial follicle survival of goat ovarian tissue after vitrification and transplantation on chorioallanthoic membrane

“…ROS activation induce PTEN inhibition which increase Akt phosphorylation (p-Akt). An increase in p-Akt lead to disruption of DNA damage response resulting in BAX accumulation in cell mitochondria and initiates apoptosis process [31].…”

What Is the Best Regimen for Ovarian Stimulation of Poor Responders in ART/IVF?

“…The IVA approach promotes growth of residual ovarian follicles following ovarian tissue fragmentation leading to Hippo signaling disruption, together with in-vitro incubation with follicle activating stimulators (114)(115)(116)(117). However, the IVA method has been considered equivocal regarding its efficacy and safety whereas in vitro studies have suggested that activation by pharmacological methods may negatively affect oocytes' quality (118)(119)(120)(121). Indeed, it has been suggested that IVA combined with PI3K/Akt and Hippo signaling pathways before ovarian slices auto-transplantation may bear major negative consequences on follicle health (118,(122)(123)(124)(125).…”

“…However, the IVA method has been considered equivocal regarding its efficacy and safety whereas in vitro studies have suggested that activation by pharmacological methods may negatively affect oocytes' quality (118)(119)(120)(121). Indeed, it has been suggested that IVA combined with PI3K/Akt and Hippo signaling pathways before ovarian slices auto-transplantation may bear major negative consequences on follicle health (118,(122)(123)(124)(125).…”