scholarly journals Sirt1 sustains female fertility by slowing age‐related decline in oocyte quality required for post‐fertilization embryo development

Aging Cell ◽  
2020 ◽  
Vol 19 (9) ◽  
Author(s):  
Juvita D. Iljas ◽  
Zhe Wei ◽  
Hayden A. Homer
Keyword(s):  
Embryo Development ◽  
Oocyte Quality ◽  
Female Fertility ◽  
Age Related

Impact of endoplasmic reticulum stress on oocyte aging mechanisms

2020 ◽  
Vol 26 (8) ◽  
pp. 567-575
Author(s):  
Isao Takehara ◽  
Hideki Igarashi ◽  
Jun Kawagoe ◽  
Koki Matsuo ◽  
Kyoko Takahashi ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Embryo Development ◽  
Oocyte Quality ◽  
Initiation Factor ◽  
Aged Mouse ◽  
Age Related ◽  
Initiation Factor 2 ◽  
Aging Mechanisms

Abstract Endoplasmic reticulum (ER) stress is associated with several aging-related diseases; however, the mechanism underlying age-related deterioration of oocyte quality is unclear. Here, we used post-ovulatory, in vivo aged mouse oocytes as a model. Super-ovulated oocytes harvested from the oviduct at 14 h and 20 h post-hCG injection were designated as ‘fresh’ and ‘aged’, respectively. Embryo development following IVF was compared between fresh, aged and ER stress-induced oocytes. Expression of the ER stress marker GRP78 was examined at each stage. To evaluate the effect of salubrinal, an ER stress suppressor, on embryo development following IVF, expression levels of GRP78 and phospho-eukaryotic initiation factor 2 alpha were compared between aged and salubrinal-treated aged oocytes. Embryo transfer of salubrinal-treated aged oocytes was performed to examine the safety of salubrinal. Similar to aged oocytes, ER stress-induced oocytes showed lower fertilization rates and poor embryo development. Following IVF, expression of GRP78 decreased with embryo development. GRP78 expression was significantly higher in aged oocytes than in fresh oocytes. Salubrinal lowered GRP78 levels and improved embryo development. No adverse effect of salubrinal treatment was found on the birth weight of pups or on organogenesis in mice. The limitation of this study was that protein kinase-like ER kinase was the only ER stress pathway examined; the role of IRE1 and ATF6 pathways was not considered. Nevertheless, salubrinal can significantly improve embryo development in in vivo aged oocytes undergoing ER stress. Hence, regulation of ER stress might represent a promising therapeutic strategy to overcome poor oocyte quality.

scholarly journals Ovarian ageing and the impact on female fertility

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1835 ◽  
Author(s):  
Beverley Vollenhoven ◽  
Sarah Hunt
Keyword(s):  
Predictive Models ◽  
Current Knowledge ◽  
Threshold Level ◽  
Oocyte Quality ◽  
Female Fertility ◽  
Menopausal Transition ◽  
Oocyte Number ◽  
Age Related ◽  
The Impact

Female fertility decreases with increasing age, a reflection of declining oocyte quantity and quality. The menopausal transition occurs when the oocyte quantity falls below a threshold level. The pattern of follicular depletion as well as the factors, timing and mechanisms surrounding both declining oocyte number and oocyte quality remain incompletely understood. Further studies are needed to examine the factors involved and develop predictive models and biomarkers to assist in the management of age-related subfertility. This review summarises the current knowledge addressing the ageing ovary and its impact on fertility.

126 Subcortical maternal complex (SCMC) expression during folliculogenesis is affected by oocyte donor age in sheep

2020 ◽  
Vol 32 (2) ◽  
pp. 190
Author(s):  
D. Bebbere ◽  
A. Abazari-Kia ◽  
F. Ariu ◽  
L. Bogliolo ◽  
S. Ledda
Keyword(s):  
Molecular Mechanisms ◽  
Oocyte Quality ◽  
Arginine Deiminase ◽  
Female Fertility ◽  
Developmental Competence ◽  
Donor Age ◽  
Oocyte Growth ◽  
Aberrant Expression ◽  
Pyrin Domain ◽  
Age Related

Age-associated decline in female fertility is largely attributable to decrease in oocyte quality. However, the molecular mechanisms that shape oocyte developmental competence, and that may be involved in reproductive aging, are yet to be elucidated. The subcortical maternal complex (SCMC) is a multiprotein complex located in the subcortex of oocytes that is essential for early embryogenesis and female fertility. It appears to be functionally conserved across mammals; aberrant expression of its members was observed in several animal models of differential competence, and mutations in human SCMC genes were associated with certain human reproductive disorders. At least seven proteins contribute to the complex: KH domain-containing 3 like (KHDC3/FILIA), NLR family pyrin domain-containing 2 (NLRP2), NLRP5 (MATER), oocyte expressed protein (OOEP), peptidyl arginine deiminase 6 (PADI6), transducin-like enhancer of split 6 (TLE6), and zinc finger BED-type-containing 3 (ZBED3), all encoded by maternal effect genes (MEGs). The aim of the present work was to evaluate expression dynamics of the SCMC components during folliculogenesis in relation to maternal age in sheep. Total RNA was isolated and reverse-transcribed from pools of denuded growing oocytes (GO) of different diameters (70-90μm (small, S), 90-110μm (medium, M), or 110-130μm (large, L)) derived from nonhormonally treated prepubertal (Pr, age 40 days), adult (Ad, age <4 years), or aged (Aged, age >6 years) animals (5 pools of 30 oocytes per experimental group). The SCMC expression was assessed by real-time PCR (PCR efficiency of 90-110% and correlation coefficient r2>0.99). Data were normalized against oocyte number and an exogenous spike-in mRNA, Luciferase, as reference gene. Expression dynamics were analyzed within each age group (general linear model ANOVA). Strikingly, patterns specifically associated with donor age were observed during folliculogenesis for six of the seven SCMC components. The Pr group showed active transcription of all mRNA, except ZBED3, during the entire window of oocyte growth (P<0.05). On the contrary, the similar abundance of NLRP2, NLRP5, PADI6, and ZBED3 in Ad S, M, and L GO suggests earlier storage during folliculogenesis; FILIA, OOEP, and TLE6 showed an increase between Ad S and M GO (P<0.05), indicating that the synthesis of these transcripts is complete at this stage (M GOs). Notably, oocytes derived from Aged donors showed a completely inverse expression pattern, with a decrease in abundance of NLRP2, TLE6, FILIA, and PADI6 mRNAs during the last stage of oocyte growth (L GO; P<0.05). Interestingly, MATER showed very high variability in expression (standard error (SE) ranging from 0.79 to 1.13 quantitation cycles (Cq)) in Aged GO, compared to Ad GO (SE 0.16-0.24 Cq) or Pr GO (SE 0.16-0.26 Cq), suggesting large inter-oocyte differences. In conclusion, age affects the storage of the MEGs encoding the SCMC during folliculogenesis. The observed depletion in SCMC transcripts in GO of aged donors is likely to be involved in the age-related decline in oocyte quality.

Poor oocyte quality rather than implantation failure as a cause of age-related decline in female fertility

The Lancet ◽  
1991 ◽  
Vol 337 (8754) ◽  
pp. 1375-1377 ◽  
Author(s):  
D. Navot ◽  
R.A. Bergh ◽  
M.A. Williams ◽  
G.J. Garrisi ◽  
I. Guzman ◽  
...  
Keyword(s):  
Oocyte Quality ◽  
Female Fertility ◽  
Implantation Failure ◽  
Age Related

Poor Oocyte Quality Rather Than Implantation Failure as a Cause of Age-Related Decline in Female Fertility

1991 ◽  
Vol 46 (10) ◽  
pp. 717-718
Author(s):  
DANIEL NAVOT ◽  
PAUL A. BERGH ◽  
MARY ANNE WILLIAMS ◽  
G. JOHN GARRISI ◽  
IDA GUZMAN ◽  
...  
Keyword(s):  
Oocyte Quality ◽  
Female Fertility ◽  
Implantation Failure ◽  
Age Related

Poor oocyte quality rather than implantation failure as a cause of age-related decline in female fertility

1992 ◽  
Vol 38 (1) ◽  
pp. 72-72
Author(s):  
D Navot ◽  
PA Bergh ◽  
MA Williams ◽  
GJ Garrisi ◽  
L Guzman ◽  
...  
Keyword(s):  
Oocyte Quality ◽  
Female Fertility ◽  
Implantation Failure ◽  
Age Related

scholarly journals Constitutive Expression of TERT Enhances β-Klotho Expression and Improves Age-Related Deterioration in Early Bovine Embryos

2021 ◽  
Vol 22 (10) ◽  
pp. 5327
Author(s):  
Lianguang Xu ◽  
Muhammad Idrees ◽  
Myeong-Don Joo ◽  
Tabinda Sidrat ◽  
Yiran Wei ◽  
...  
Keyword(s):  
Granulosa Cells ◽  
Constitutive Expression ◽  
Growth Factor Receptor ◽  
Oocyte Quality ◽  
Low Fertility ◽  
Treatment Groups ◽  
Age Related ◽  
Early Embryos ◽  
Plasmid Injection ◽  
Telomere Lengthening

Age-associated decline in oocyte quality is one of the dominant factors of low fertility. Aging alters several key processes, such as telomere lengthening, cell senescence, and cellular longevity of granulosa cells surrounding oocyte. To investigate the age-dependent molecular changes, we examined the expression, localization, and correlation of telomerase reverse transcriptase (TERT) and β-Klotho (KLB) in bovine granulosa cells, oocytes, and early embryos during the aging process. Herein, cumulus-oocyte complexes (COCs) obtained from aged cows (>120 months) via ovum pick-up (OPU) showed reduced expression of β-Klotho and its co-receptor fibroblast growth factor receptor 1 (FGFR1). TERT plasmid injection into pronuclear zygotes not only markedly enhanced day-8 blastocysts’ development competence (39.1 ± 0.8%) compared to the control (31.1 ± 0.5%) and D-galactose (17.9 ± 1.0%) treatment groups but also enhanced KLB and FGFR1 expression. In addition, plasmid-injected zygotes displayed a considerable enhancement in blastocyst quality and implantation potential. Cycloastragenol (CAG), an extract of saponins, stimulates telomerase enzymes and enhances KLB expression and alleviates age-related deterioration in cultured primary bovine granulosa cells. In conclusion, telomerase activation or constitutive expression will increase KLB expression and activate the FGFR1/β-Klotho pathway in bovine granulosa cells and early embryos, inhibiting age-related malfunctioning.

scholarly journals Molecular Mechanisms Responsible for Increased Vulnerability of the Ageing Oocyte to Oxidative Damage

2017 ◽  
Vol 2017 ◽  
pp. 1-22 ◽  
Author(s):  
Bettina P. Mihalas ◽  
Kate A. Redgrove ◽  
Eileen A. McLaughlin ◽  
Brett Nixon
Keyword(s):  
Oxidative Damage ◽  
Molecular Mechanisms ◽  
Spindle Assembly Checkpoint ◽  
Assisted Reproductive Technologies ◽  
Reproductive Technologies ◽  
Oocyte Quality ◽  
Protein Repair ◽  
Protective Mechanisms ◽  
Pronounced Increase ◽  
Age Related

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.

scholarly journals Telomere Dysfunction in Oocytes and Embryos From Obese Mice

2021 ◽  
Vol 9 ◽  
Author(s):  
Juan Ge ◽  
Congyang Li ◽  
Hongzheng Sun ◽  
Yongan Xin ◽  
Shuai Zhu ◽  
...  
Keyword(s):  
Embryo Development ◽  
High Frequency ◽  
High Fat Diet ◽  
Maternal Obesity ◽  
Oocyte Quality ◽  
Telomere Dysfunction ◽  
Obese Mice ◽  
High Fat ◽  
Telomere Shortening ◽  
Early Embryos

Maternal obesity impairs oocyte quality and embryo development. However, the potential molecular pathways remain to be explored. In the present study, we examined the effects of obesity on telomere status in oocytes and embryos obtained from mice fed with high-fat diet (HFD). Of note, telomere shortening was observed in both oocytes and early embryos from obese mice, as evidenced by the reduced expression of telomerase reverse transcriptase and activity of telomerase. Moreover, quantitative analysis of telomere dysfunction-induced foci (TIFs) revealed that maternal obesity induces the defective telomeres in oocytes and embryos. Meanwhile, the high frequency of aneuploidy was detected in HFD oocytes and embryos as compared to controls, accompanying with the increased incidence of apoptotic blastocysts. In conclusion, these results indicate that telomere dysfunction might be a molecular pathway mediating the effects of maternal obesity on oocyte quality and embryo development.

scholarly journals Effect of Follicular Fluid Oxidative Stress on Subsequent Oocyte Quality and Embryo Development

2016 ◽  
Vol 26 (1) ◽  
pp. 1-6
Author(s):  
Özgür BİGE ◽  
Bülent GÜLEKLİ ◽  
Ahmet DEMİR ◽  
Funda GÖDE ◽  
Semra KOÇTÜRK ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Embryo Development ◽  
Follicular Fluid ◽  
Oocyte Quality
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