scholarly journals The role of mitophagy during oocyte aging in human, mouse and Drosophila; implications for oocyte quality and mitochondrial disease

2021 ◽  
Author(s):  
Rachel T. Cox ◽  
Joanna Poulton ◽  
Suzannah Alice Williams
Keyword(s):  
Molecular Mechanisms ◽  
Assisted Reproductive Technologies ◽  
Reproductive Technologies ◽  
Oocyte Quality ◽  
Model Systems ◽  
Cellular Mechanisms ◽  
Older Mothers ◽  
Mtdna Mutations ◽  
Age Related ◽  
Maternal Aging

There is a worldwide trend for women to have their first pregnancy later in life. However, as oocyte quality declines with maternal aging, this trend leads to an increase in subfertility. The cellular mechanisms underlying this decline in oocyte competence are poorly understood. Oocyte mitochondria are the subcellular organelles that supply the energy that drives early embryogenesis, and thus their quality is critical for successful conception. Mitochondria contain their own DNA (mtDNA) and mutations in mtDNA cause mitochondrial diseases with severe symptoms, such as neurodegeneration and heart disease. Since mitochondrial function declines in tissues as humans age accompanied by an accumulation of mtDNA mutations, mtDNA is implicated as a cause of declining oocyte quality in older mothers. While this mutation load could be caused by declining accuracy of the mitochondrial replisome, age-related decline in mitochondrial quality control likely contributes however knowledge is lacking. Mitophagy, a cellular process which specifically targets and recycles damaged mitochondria, may be involved, but studies are scarce. And although assisted reproductive technologies (ART) can help older mothers, how these techniques affect the mechanisms that regulate mitochondrial and oocyte quality have not been studied. With the long-term goal of understanding the molecular mechanisms that control mitochondrial quality in the oocyte, model systems including Drosophila and mouse as well as human oocytes have been used. In this review we explore the contribution of mitophagy to oocyte quality and the need for further systematic investigation in oocytes during maternal aging using different systems.

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 TERRA: A Novel Biomarker of Embryo Quality and Art Outcome

Genes ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 475
Author(s):  
Maria Santa Rocca ◽  
Ludovica Dusi ◽  
Andrea Di Nisio ◽  
Erminia Alviggi ◽  
Benedetta Iussig ◽  
...  
Keyword(s):  
Telomere Length ◽  
Dna Sequences ◽  
Male Fertility ◽  
Embryo Quality ◽  
Assisted Reproductive Technologies ◽  
Biological Clock ◽  
Reproductive Technologies ◽  
Age Related ◽  
Non Coding Rna ◽  
First Time

Telomeres are considered to be an internal biological clock, and their progressive shortening has been associated with the risk of age-related diseases and reproductive alterations. Over recent years, an increasing number of studies have focused on the association between telomere length and fertility, identifying sperm telomere length (STL) as a novel biomarker of male fertility. Although typically considered to be repeated DNA sequences, telomeres have recently been shown to also include a long non-coding RNA (lncRNA) known as TERRA (telomeric repeat-containing RNAs). Interestingly, males with idiopathic infertility show reduced testicular TERRA expression, suggesting a link between TERRA and male fertility. The aim of this study was to investigate the role of seminal TERRA expression in embryo quality. To this end, STL and TERRA expression were quantified by Real Time qPCR in the semen of 35 men who underwent assisted reproductive technologies (ART) and 30 fertile men. We found that TERRA expression in semen and STL was reduced in patients that underwent ART (both p < 0.001). Interestingly, TERRA and STL expressions were positively correlated (p = 0.010), and TERRA expression was positively associated with embryo quality (p < 0.001). These preliminary findings suggest a role for TERRA in the maintenance of sperm telomere integrity during gametogenesis, and for the first time, TERRA expression was found as a predictive factor for embryo quality in the setting of assisted reproduction.

Changes in Twinning Rates in South Korea: 1981–2002

2005 ◽  
Vol 8 (1) ◽  
pp. 76-79 ◽  
Author(s):  
Yoon-Mi Hur ◽  
Jun Soo Kwon
Keyword(s):  
South Korea ◽  
Assisted Reproductive Technologies ◽  
Reproductive Technologies ◽  
Rapid Rise ◽  
The South ◽  
Older Mothers ◽  
South Korean ◽  
Record Data ◽  
Birth Data ◽  
National Statistical Office

AbstractThe present study investigates the twinning rate trends in South Korea for the years 1981 to 2002 utilizing the birth record data from the South Korea National Statistical Office. The twinning rates between 1981 and 1991 remained nearly constant and were slightly less than 10 twin individuals, that is, approximately five pairs per thousand births. Since the early 1990s, however, the twinning rate has increased sharply and reached 19.30 twin individuals, that is, around 10 pairs per thousand births in the year 2002. Application of the Weinberg method to birth data for the years 2000 to 2002 revealed that the dizygotic twin rate in South Korea increased almost threefold between 1981 to 1991 and 2002. In the 1980s the effect of maternal age on twinning rates appeared to be minimal. In the 1990s, however, increases in twinning rates occurred more markedly among older mothers than among younger mothers. We speculate that the rapid rise in twinning rates in South Korea in the 1990s is probably attributable to the spread of Assisted Reproductive Technologies among older mothers who seek treatments for infertility. The present study also examined whether residing in industrial areas is associated with multiple births in the South Korean population. The results did not support the recent finding of higher twinning incidence in industrialized regions.

scholarly journals Endometrial receptivity: the molecularmechanisms regulation of implantation

2013 ◽  
Vol 62 (2) ◽  
pp. 63-74 ◽  
Author(s):  
Yuliya Sergeyevna Krylova ◽  
Igor Moiseyevich Kvetnoy ◽  
Eduard Karpovich Aylamazyan
Keyword(s):  
Parameter Estimation ◽  
Molecular Mechanisms ◽  
Assisted Reproductive Technologies ◽  
Reproductive Technologies ◽  
Signaling Molecules ◽  
Endometrial Receptivity

Presents current views on endometrial receptivity and the molecular mechanisms regulation of implantation. Examines the signaling molecules as potential markers of parameter estimation window of implantation in assisted reproductive technologies.

scholarly journals How to Achieve High-Quality Oocytes? The Key Role of Myo-Inositol and Melatonin

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Salvatore Giovanni Vitale ◽  
Paola Rossetti ◽  
Francesco Corrado ◽  
Agnese Maria Chiara Rapisarda ◽  
Sandro La Vignera ◽  
...  
Keyword(s):  
Assisted Reproductive Technologies ◽  
Reproductive Technologies ◽  
Oocyte Quality ◽  
Fertilization Rate ◽  
In Vitro Models ◽  
The One ◽  
High Level

Assisted reproductive technologies (ART) have experienced growing interest from infertile patients seeking to become pregnant. The quality of oocytes plays a pivotal role in determining ART outcomes. Although many authors have studied how supplementation therapy may affect this important parameter for both in vivo and in vitro models, data are not yet robust enough to support firm conclusions. Regarding this last point, in this review our objective has been to evaluate the state of the art regarding supplementation with melatonin and myo-inositol in order to improve oocyte quality during ART. On the one hand, the antioxidant effect of melatonin is well known as being useful during ovulation and oocyte incubation, two occasions with a high level of oxidative stress. On the other hand, myo-inositol is important in cellular structure and in cellular signaling pathways. Our analysis suggests that the use of these two molecules may significantly improve the quality of oocytes and the quality of embryos: melatonin seems to raise the fertilization rate, and myo-inositol improves the pregnancy rate, although all published studies do not fully agree with these conclusions. However, previous studies have demonstrated that cotreatment improves these results compared with melatonin alone or myo-inositol alone. We recommend that further studies be performed in order to confirm these positive outcomes in routine ART treatment.

scholarly journals Cellular and molecular mechanisms underlying muscular dystrophy

2013 ◽  
Vol 201 (4) ◽  
pp. 499-510 ◽  
Author(s):  
Fedik Rahimov ◽  
Louis M. Kunkel
Keyword(s):  
Muscular Dystrophy ◽  
Molecular Mechanisms ◽  
Muscle Wasting ◽  
Neuromuscular Disorders ◽  
Genetic Diseases ◽  
Model Systems ◽  
Cellular Mechanisms ◽  
Gene Encoding ◽  
Progressive Degeneration ◽  
Molecular Pathomechanisms

The muscular dystrophies are a group of heterogeneous genetic diseases characterized by progressive degeneration and weakness of skeletal muscle. Since the discovery of the first muscular dystrophy gene encoding dystrophin, a large number of genes have been identified that are involved in various muscle-wasting and neuromuscular disorders. Human genetic studies complemented by animal model systems have substantially contributed to our understanding of the molecular pathomechanisms underlying muscle degeneration. Moreover, these studies have revealed distinct molecular and cellular mechanisms that link genetic mutations to diverse muscle wasting phenotypes.

scholarly journals Sperm oxidative stress: clinical significance and management

2021 ◽  
pp. 19-27
Author(s):  
S. I. Gamidov ◽  
T. V. Shatylko ◽  
A. Yu. Popova ◽  
N. G. Gasanov ◽  
R. S. Gamidov
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Reproductive System ◽  
Molecular Mechanisms ◽  
Assisted Reproductive Technologies ◽  
Reactive Oxygen ◽  
Reproductive Technologies ◽  
Male Reproductive System ◽  
Antioxidant Systems ◽  
Oxygen Species

Oxidative stress is one of the leading causes of sperm dysfunction. Excessive amounts of reactive oxygen species can damage sperm membranes and disrupt their DNA integrity, which affects not only the likelihood of getting pregnant naturally, but also the clinical outcomes of assisted reproductive technologies and the risk of miscarriage. Sperm cells are extremely vulnerable to oxidative stress, given the limited functional reserve of their antioxidant systems and the DNA repair apparatus. Lifestyle factors, most of which are modifiable, often trigger generation of reactive oxygen species.  Both the lifestyle modification and use of antioxidant dietary supplements are adequate and compatible ways to combat male oxidative stress-associated infertility. The search for other internal and external sources of reactive oxygen species, the identification of the etiology of oxidative stress and treatment of respective diseases are necessary for the successful regulation of redox processes in the male reproductive system in clinical practice, which is required not only to overcome infertility, but also to prevent induced epigenetic disorders in subsequent generations. The article presents the analysis of the molecular mechanisms of male idiopathic infertility. The authors provide an overview of how to prevent oxidative stress as one of the causes of subfebrile fever. The article provides an overview of modern therapeutics, as well as the options for eliminating the consequences of the effect of reactive oxygen species on spermatogenesis and male reproductive system in general.

scholarly journals Reproductive technologies, female infertility, and the risk of imprinting-related disorders

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Patricia Fauque ◽  
Jacques De Mouzon ◽  
Aviva Devaux ◽  
Sylvie Epelboin ◽  
Marie-José Gervoise-Boyer ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Assisted Reproductive Technologies ◽  
Intrauterine Insemination ◽  
Reproductive Technologies ◽  
Female Infertility ◽  
Global Risk ◽  
Vitro Fertilization ◽  
Increased Risk ◽  
Genomic Imprints

Abstract Background Epidemiological studies suggest that singletons born from assisted reproductive technologies (ART) have a high risk of adverse perinatal outcomes, specifically for imprinting disorders. Because ART processes take place at times when epigenetic reprogramming/imprinting are occurring, there is concern that ART can affect genomic imprints. However, little is currently known about the risk of imprinting defects according to the type of ART or the type of underlying female infertility. From the French national health database, a cohort of 3,501,495 singletons born over a 5-year period (2013–2017) following fresh embryo or frozen embryo transfers (fresh-ET or FET from in vitro fertilization), intrauterine insemination, or natural conception was followed up to early childhood. Based on clinical features, several syndromes/diseases involving imprinted genes were monitored. The effects of ART conception and the underlying cause of female infertility were assessed. Results Compared with infants conceived naturally, children born after fresh-ET had a higher prevalence of imprinting-related diseases, with an aOR of 1.43 [95% CI 1.13–1.81, p = 0.003]. Namely, we observed an increased risk of neonatal diabetes mellitus (1.96 aOR [95% CI 1.43–2.70], p < 0.001). There was an overall independent increase in risk of imprinting diseases for children with mothers diagnosed with endometriosis (1.38 aOR [95% CI 1.06–1.80], p = 0.02). Young and advanced maternal age, primiparity, obesity, smoking, and history of high blood pressure or diabetes were also associated with high global risk. Conclusions This prospective epidemiological study showed that the risk of clinically diagnosed imprinting-related diseases is increased in children conceived after fresh embryo transfers or from mothers with endometriosis. The increased perturbations in genomic imprinting could be caused by controlled ovarian hyperstimulation and potentially endometriosis through the impairment of endometrial receptivity and placentation, leading to epigenetic feto-placental changes. Further studies are now needed to improve understanding of the underlying molecular mechanisms (i.e. genetic or epigenetic causes).

scholarly journals Quercetin promotes in vitro maturation of oocytes from humans and aged mice

2020 ◽  
Vol 11 (11) ◽  
Author(s):  
Yongzhi Cao ◽  
Haibin Zhao ◽  
Zhao Wang ◽  
Changming Zhang ◽  
Yuehong Bian ◽  
...  
Keyword(s):  
In Vitro Maturation ◽  
Formation Rate ◽  
Reproductive Technologies ◽  
Oocyte Quality ◽  
Chromosome Morphology ◽  
Cortical Granule ◽  
Success Rates ◽  
Aged Mice ◽  
Age Related

Abstract Maternal fertility declines irreversibly with aging, and advanced maternal age is mostly related to impaired oocyte quality. The flavonol compound quercetin is considered to be an anti-aging agent due to its cytoprotective actions as an antioxidant. However, its role and mechanisms on aged oocytes are unclear. In this study, the quercetin promotes in vitro maturation (IVM) and early embryonic development of oocytes from aged mice. It is extended these findings in human oocytes, showing that quercetin promotes the IVM rate by 19.6% and increases the blastocyst formation rate by 15.5% compared to untreated controls. The overall oocyte quality of aged mice is improved by quercetin treatment, assessed as spindle/chromosome morphology and cortical granule distribution. Mitochondria is the primary endogenous source of age-related oxidative stress, and an RNA-seq analysis of quercetin-treated oocytes reveals molecular insights including scavenged mitochondrial-ROS, reduced apoptosis, and improved autophagy. Further, this study demonstrates that quercetin reduces ROS via SIRT3-mediated acetylation of SOD2’s K68 residue. Thus, beyond demonstrating that quercetin confers beneficial mitochondria-related impacts in aged oocytes, this study illustrates a potential strategy to prevent or delay oocyte aging and to improve success rates of assisted human reproductive technologies (ART).

Anti-Mullerian hormone and its predictive value for assessing oocyte quality

GYNECOLOGY ◽  
2020 ◽  
Vol 22 (6) ◽  
pp. 21-26
Author(s):  
Natalia V. Aleksandrova
Keyword(s):  
Ovarian Reserve ◽  
Predictive Value ◽  
Assisted Reproductive Technologies ◽  
Reproductive Technologies ◽  
Oocyte Quality ◽  
Laboratory Markers ◽  
Diagnostic Capabilities ◽  
First Time

The article systematizes information on the diagnostic capabilities of modern clinical and laboratory markers of ovarian reserve. The diagnostic capabilities of anti-Mllerian hormone (AMH) as a marker of ovarian reserve are discussed, which make it possible to adjust the dose of hormonal drugs and predict the response of the ovary to stimulation in programs of assisted reproductive technologies. This paper discusses for the first time the role of AMH in assessing the quality of oocytes and subsequent embryos. Despite insufficient literature data, further study of AMH, as well as full-scale research in this direction, seems to be extremely promising.

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