Direct Single-Cell Analysis of Human Polar Bodies and Cleavage-Stage Embryos Reveals No Evidence of the Telomere Theory of Reproductive Ageing in Relation to Aneuploidy Generation

Turner, Kara; Lynch, Colleen; Rouse, Hannah; Vasu, Vimal; Griffin, Darren K.

doi:10.3390/cells8020163

Cited by 10 publications

(4 citation statements)

References 59 publications

(88 reference statements)

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“…In reproductively aged mouse oocytes, Q-PCR and quantitative fluorescence in situ hybridization analyses show significant increase of OS and shortening of telomere lengths (6, 87). Human oocytes with shorter telomeres develop into more fragmented and more aneuploid preimplantation embryos with lower implantation rates (88, 89), whereas relative telomere length was comparable in aneuploid and euploid first polar bodies and blastomeres (90). Further, SIRT6, associated with oxidative homeostasis, has been identified as an important modulator of telomeres in age-related deterioration of mouse oocytes (91, 92).…”

Section: Introductionmentioning

confidence: 99%

Impact of Oxidative Stress on Age-Associated Decline in Oocyte Developmental Competence

et al. 2019

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Reproductive capacity in women starts to decline beyond their mid-30s and pregnancies in older women result in higher rates of miscarriage with aneuploidy. Age-related decline in fertility is strongly attributed to ovarian aging, diminished ovarian reserves, and decreased developmental competence of oocytes. In this review, we discuss the underlying mechanisms of age-related decline in oocyte quality, focusing on oxidative stress (OS) in oocytes. The primary cause is the accumulation of spontaneous damage to the mitochondria arising from increased reactive oxygen species (ROS) in oocytes, generated by the mitochondria themselves during daily biological metabolism. Mitochondrial dysfunction reduces ATP synthesis and influences the meiotic spindle assembly responsible for chromosomal segregation. Moreover, reproductively aged oocytes produce a decline in the fidelity of the protective mechanisms against ROS, namely the ROS-scavenging metabolism, repair of ROS-damaged DNA, and the proteasome and autophagy system for ROS-damaged proteins. Accordingly, increased ROS and increased vulnerability of oocytes to ROS lead to spindle instability, chromosomal abnormalities, telomere shortening, and reduced developmental competence of aged oocytes.

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Section: Introductionmentioning

confidence: 99%

Impact of Oxidative Stress on Age-Associated Decline in Oocyte Developmental Competence

et al. 2019

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“…Indeed, cumulus cell telomeres are significantly longer than leukocyte telomeres [Lara-Molina et al, 2020] which may be a result of a unique "coping strategy" in follicles to protect against telomere shortening. Finally, embryo polar body and blastomere biopsies have shown no correlation between TL and female age, or between embryo aneuploid status and age [Turner et al, 2019]. As such, the ovarian germ cell microenvironment may employ other means of protecting and preserving telomeres than what is established in somatic tissues.…”

Section: Telomere Shorteningmentioning

confidence: 99%

The Aging Ovary and the Tales Learned Since Fetal Development

Lopez,

Hohensee,

Liang

et al. 2023

Sex Dev

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Background: While the term “aging” implies a process typically associated with later life, the consequences of ovarian aging are evident by the time a woman reaches her forties, and sometimes earlier. This is due to a gradual decline in the quantity and quality of oocytes which occurs over a woman’s reproductive lifespan. Indeed, the reproductive potential of the ovary is established even before birth, as the proper formation and assembly of the ovarian germ cell population during fetal life determines the lifetime endowment of oocytes and follicles. In the ovary, sophisticated molecular processes have been identified that regulate the timing of ovarian aging and these are critical to ensuring follicular maintenance. Summary: The mechanisms thought to contribute to overall aging have been summarized under the term the “hallmarks of aging” and include such processes as DNA damage, mitochondrial dysfunction, telomere attrition, genomic instability, and stem cell exhaustion, among others. Similarly, in the ovary, molecular processes have been identified that regulate the timing of ovarian aging and these are critical to ensuring follicular maintenance. In this review, we outline critical processes involved in ovarian aging, highlight major achievements for treatment of ovarian aging, and discuss ongoing questions and areas of debate. Key Messages: Ovarian aging is recognized as what may be a complex process in which age, genetics, environment, and many other factors contribute to the size and depletion of the follicle pool. The putative hallmarks of reproductive aging outlined herein include a diversity of plausible processes contributing to the depletion of the ovarian reserve. More research is needed to clarify if and to what extent these putative regulators do in fact govern follicle and oocyte behavior, and how these signals might be integrated in order to control the overall pattern of ovarian aging.

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“…There was no difference in relative telomere length between aneuploid and haploid first polar bodies and the oogonium, indicating that telomere shortening is unrelated to chromosome segregation errors in oogenesis-stage embryos. This study's conclusion that telomere shortening is unrelated to ovarian aging in women may be attributable to the limited age range of its sample mothers (most were concentrated in the 30–40 years) [120].…”

Section: The Findings Of Single-cell Studies In Physiology Of Follicu...mentioning

confidence: 99%

Follicular development and ovary aging: single-cell studies

Zhao

Wang

Yang

2023

Biology of Reproduction

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Follicular development is a critical process in reproductive biology that determines the number of oocytes and interacts with various cells within the follicle (such as oocytes, granulosa cells, cumulus cells and theca cells, etc.), and plays a vital role in fertility and reproductive health due to the dogma of a limited number of oogonia. Dysregulation of follicular development can lead to infertility problems and other reproductive disorders. To explore the physiological and pathological mechanisms of follicular development, immunology-based methods, microarrays, and next-generation sequencing have traditionally been used for characterization at the tissue level. However, with the proliferation of single-cell sequencing techniques, research has uncovered unique molecular mechanisms in individual cells that have been masked by previous holistic analyses. In this review, we briefly summarize the achievements and limitations of traditional methods in the study of follicular development. Simultaneously, we focus on how to understand the physiological process of follicular development at the single-cell level and reveal the relevant mechanisms leading to the pathology of follicular development and intervention targets. Moreover, we also summarize the limitations and application prospects of single cell sequencing in follicular development research.

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Direct Single-Cell Analysis of Human Polar Bodies and Cleavage-Stage Embryos Reveals No Evidence of the Telomere Theory of Reproductive Ageing in Relation to Aneuploidy Generation

Cited by 10 publications

References 59 publications

Impact of Oxidative Stress on Age-Associated Decline in Oocyte Developmental Competence

Impact of Oxidative Stress on Age-Associated Decline in Oocyte Developmental Competence

The Aging Ovary and the Tales Learned Since Fetal Development

Follicular development and ovary aging: single-cell studies

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