TY - JOUR
T1 - Molecular mechanisms responsible for increased vulnerability of the ageing oocyte to oxidative damage
AU - Mihalas, Bettina P.
AU - Redgrove, Kate A.
AU - McLaughlin, Eileen A.
AU - Nixon, Brett
N1 - Funding Information:
This work was supported by the University of Newcastle’s Priority Research Centre for Reproductive Science and the Hunter Medical Research Institute’s Pregnancy and Reproduction Program. Bettina P. Mihalas is a recipient of a Research Training Program Scholarship and an Emlyn and Jennie Thomas Postgraduate Medical Research Scholarship.
Publisher Copyright:
© 2017 Bettina P. Mihalas et al.
PY - 2017/10/18
Y1 - 2017/10/18
N2 - In their midthirties, women experience a decline in fertility, coupled to a pronounced increase in the risk of aneuploidy, miscarriage, and birth defects. Although the aetiology of such pathologies are complex, a causative relationship between the age-related decline in oocyte quality and oxidative stress (OS) is now well established. What remains less certain are the molecular mechanisms governing the increased vulnerability of the aged oocyte to oxidative damage. In this review, we explore the reduced capacity of the ageing oocyte to mitigate macromolecular damage arising from oxidative insults and highlight the dramatic consequences for oocyte quality and female fertility. Indeed, while oocytes are typically endowed with a comprehensive suite of molecular mechanisms to moderate oxidative damage and thus ensure the fidelity of the germline, there is increasing recognition that the efficacy of such protective mechanisms undergoes an age-related decline. For instance, impaired reactive oxygen species metabolism, decreased DNA repair, reduced sensitivity of the spindle assembly checkpoint, and decreased capacity for protein repair and degradation collectively render the aged oocyte acutely vulnerable to OS and limits their capacity to recover from exposure to such insults. We also highlight the inadequacies of our current armoury of assisted reproductive technologies to combat age-related female infertility, emphasising the need for further research into mechanisms underpinning the functional deterioration of the ageing oocyte.
AB - In their midthirties, women experience a decline in fertility, coupled to a pronounced increase in the risk of aneuploidy, miscarriage, and birth defects. Although the aetiology of such pathologies are complex, a causative relationship between the age-related decline in oocyte quality and oxidative stress (OS) is now well established. What remains less certain are the molecular mechanisms governing the increased vulnerability of the aged oocyte to oxidative damage. In this review, we explore the reduced capacity of the ageing oocyte to mitigate macromolecular damage arising from oxidative insults and highlight the dramatic consequences for oocyte quality and female fertility. Indeed, while oocytes are typically endowed with a comprehensive suite of molecular mechanisms to moderate oxidative damage and thus ensure the fidelity of the germline, there is increasing recognition that the efficacy of such protective mechanisms undergoes an age-related decline. For instance, impaired reactive oxygen species metabolism, decreased DNA repair, reduced sensitivity of the spindle assembly checkpoint, and decreased capacity for protein repair and degradation collectively render the aged oocyte acutely vulnerable to OS and limits their capacity to recover from exposure to such insults. We also highlight the inadequacies of our current armoury of assisted reproductive technologies to combat age-related female infertility, emphasising the need for further research into mechanisms underpinning the functional deterioration of the ageing oocyte.
KW - Oxidative stress
KW - Follicular Fluid
KW - Antioxidants
UR - http://www.scopus.com/inward/record.url?scp=85042602979&partnerID=8YFLogxK
UR - http://www.mendeley.com/research/molecular-mechanisms-responsible-increased-vulnerability-ageing-oocyte-oxidative-damage
U2 - 10.1155/2017/4015874
DO - 10.1155/2017/4015874
M3 - Review article
C2 - 29312475
AN - SCOPUS:85042602979
SN - 1942-0900
VL - 2017
SP - 1
EP - 22
JO - Oxidative Medicine and Cellular Longevity
JF - Oxidative Medicine and Cellular Longevity
M1 - 4015874
ER -