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).

scholarly journals Influence of leptin on in vitro maturation and steroidogenic secretion of cumulus–oocyte complexes through JAK2/STAT3 and MEK 1/2 pathways in the rabbit model

Reproduction ◽  
2010 ◽  
Vol 139 (3) ◽  
pp. 523-532 ◽  
Author(s):  
M Arias-Álvarez ◽  
R M García-García ◽  
L Torres-Rovira ◽  
A González-Bulnes ◽  
P G Rebollar ◽  
...  
Keyword(s):  
Oocyte Maturation ◽  
Leptin Receptor ◽  
Assisted Reproductive Technologies ◽  
Rabbit Model ◽  
Reproductive Technologies ◽  
Oocyte Quality ◽  
Cortical Granule ◽  
Steroid Secretion ◽  
Ovulatory Period

Extreme body mass indexes may impair reproductive outcome in assisted reproductive technologies. Leptin reflects the amount of body fat and could act as a modulator of oocyte quality through activation of specific transcription factors. The aim of this work was to establish whether: 1) leptin influences meiotic and cytoplasmic oocyte maturation; 2) STAT3 and MAPK mediate the effects of leptin and 3) leptin modulates steroid secretion by cumulus–oocyte complexes (COC) duringin vitromaturation (IVM). We confirmed immunolocalisation of leptin receptor in oocytes, cumulus/granulosa cells during the peri-ovulatory period. The confocal study showed that COC supplemented with 1, 10 and 100 ng/ml leptin had a significantly higher metaphase II (MII) percentage than those IVM without leptin (P<0.05) and a similar MII index compared to the group supplemented with 10% FCS. Leptin did not increase the percentage of cytoplasmically matured oocytes in terms of cortical granule migration rate, whereas a significantly higher index was found in the FCS group (P<0.001). Oestradiol concentrations in spent media were higher in the FCS group compared to other treatments (P<0.001). Leptin-stimulated nuclear oocyte maturation was significantly impaired when leptin-induced JAK2/STAT3 and MEK 1/2 activation was suppressed by the inhibitors (P<0.001). Steroid secretion of COC was not affected by leptin activation of JAK2/STAT3 or MEK 1/2 pathways. In conclusion, JAK2/STAT3 and MEK 1/2 pathways mediate the enhancement of nuclear oocyte maturation by leptin; however, neither cytoplasmic oocyte maturation nor steroidogenic response of COC were improved in the present rabbit model.

027. In vitro growth and maturation: how does this technology fit for clinical application?

2005 ◽  
Vol 17 (9) ◽  
pp. 69
Author(s):  
M. Lane ◽  
C. Yeo ◽  
K. S. Cashman ◽  
H. M. Hamilton
Keyword(s):  
In Vitro Maturation ◽  
Polycystic Ovary ◽  
Oocyte Quality ◽  
Attractive Alternative ◽  
Success Rates ◽  
Human Oocytes ◽  
Vein Thrombosis

Superovulation protocols used in IVF result in multiple eggs that can be fertilized and grown in the laboratory to allow for selection of the best embryo for return to the mother, thereby increasing the chances for a successful pregnancy. However, there are many side effects of these superovulation drug protocols, such as deep vein thrombosis and hyperstimulation. The latter is of particular concern for women with polycystic ovary syndrome. Furthermore, the use of gonadotrophins has been reported to compromise both oocyte quality and the uterine environment and may contribute to the low success rates of IVF. Therefore the ability to collect large numbers of oocytes from women and mature them in vitro is an attractive alternative. However, although there are reports in the literature on extended maturation/culture periods of human oocytes the pregnancy rates are significantly lower than that observed after in vivo maturation. The ability to offer such technology is currently limited by the lack of understanding of how the conditions for in vitro maturation affect the quality of the oocyte and the resulting embryo. Our research is concentrated on establishing the role of metabolic balance in the oocyte for the maintenance of subsequent viability. We have determined that disruptions to the balance between mitochondrial and cytoplasmic metabolism in animal oocytes have significant adverse consequences for the resultant embryo. Changing conditions for in vitro maturation were also found to alter the establishment of the metabolic settings of the oocyte. The ability to determine the role of such parameters in maturing human oocytes will be important for the prospect of adoption of this technology for routine clinical practice.

scholarly journals Dill Extract Induces Elastic Fiber Neosynthesis and Functional Improvement in the Ascending Aorta of Aged Mice with Reversal of Age-Dependent Cardiac Hypertrophy and Involvement of Lysyl Oxidase-Like-1

Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 173 ◽  
Author(s):  
Wassim Fhayli ◽  
Quentin Boëté ◽  
Nadjib Kihal ◽  
Valérie Cenizo ◽  
Pascal Sommer ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Lysyl Oxidase ◽  
Elastic Fiber ◽  
Ascending Aorta ◽  
Functional Improvement ◽  
Elastic Fibers ◽  
Aged Mice ◽  
Age Related ◽  
And Function

Elastic fibers (90% elastin, 10% fibrillin-rich microfibrils) are synthesized only in early life and adolescence mainly by the vascular smooth muscle cells through the cross-linking of its soluble precursor, tropoelastin. Elastic fibers endow the large elastic arteries with resilience and elasticity. Normal vascular aging is associated with arterial remodeling and stiffening, especially due to the end of production and degradation of elastic fibers, leading to altered cardiovascular function. Several pharmacological treatments stimulate the production of elastin and elastic fibers. In particular, dill extract (DE) has been demonstrated to stimulate elastin production in vitro in dermal equivalent models and in skin fibroblasts to increase lysyl oxidase–like-1 (LOXL-1) gene expression, an enzyme contributing to tropoelastin crosslinking and elastin formation. Here, we have investigated the effects of a chronic treatment (three months) of aged male mice with DE (5% or 10% v/v, in drinking water) on the structure and function of the ascending aorta. DE treatment, especially at 10%, of aged mice protected pre-existing elastic lamellae, reactivated tropoelastin and LOXL-1 expressions, induced elastic fiber neo-synthesis, and decreased the stiffness of the aging aortic wall, probably explaining the reversal of the age-related cardiac hypertrophy also observed following the treatment. DE could thus be considered as an anti-aging product for the cardiovascular system.

scholarly journals Effect of D-Glucuronic Acid and N-acetyl-D-Glucosamine Treatment during In Vitro Maturation on Embryonic Development after Parthenogenesis and Somatic Cell Nuclear Transfer in Pigs

Animals ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 1034
Author(s):  
Joohyeong Lee ◽  
Eunhye Kim ◽  
Seon-Ung Hwang ◽  
Lian Cai ◽  
Mirae Kim ◽  
...  
Keyword(s):  
Embryonic Development ◽  
Somatic Cell ◽  
Somatic Cell Nuclear Transfer ◽  
Nuclear Transfer ◽  
In Vitro Maturation ◽  
Glucuronic Acid ◽  
Cumulus Cell ◽  
Cortical Granule ◽  
Oocyte Diameter

This study aimed to examine the effects of treatment with glucuronic acid (GA) and N-acetyl-D-glucosamine (AG), which are components of hyaluronic acid (HA), during porcine oocyte in vitro maturation (IVM). We measured the diameter of the oocyte, the thickness of the perivitelline space (PVS), the reactive oxygen species (ROS) level, and the expression of cumulus cell expansion and ROS-related genes and examined the cortical granule (CG) reaction of oocytes. The addition of 0.05 mM GA and 0.05 mM AG during the first 22 h of oocyte IVM significantly increased oocyte diameter and PVS size compared with the control (non-treatment). The addition of GA and AG reduced the intra-oocyte ROS content and improved the CG of the oocyte. GA and AG treatment increased the expression of CD44 and CX43 in cumulus cells and PRDX1 and TXN2 in oocytes. In both the chemically defined and the complex medium (Medium-199 + porcine follicular fluid), oocytes derived from the GA and AG treatments presented significantly higher blastocyst rates than the control after parthenogenesis (PA) and somatic cell nuclear transfer (SCNT). In conclusion, the addition of GA and AG during IVM in pig oocytes has beneficial effects on oocyte IVM and early embryonic development after PA and SCNT.

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.

P–219 mtDNA content in bovine cumulus cells does not predict oocytés developmental competence

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Á Martíne. Moro ◽  
I Lamas-Toranzo ◽  
L González-Brusi ◽  
A Pérez-Gómez ◽  
P Bermejo-Álvarez
Keyword(s):  
Cumulus Cell ◽  
Cumulus Cells ◽  
Oocyte Quality ◽  
Blastocyst Stage ◽  
Early Embryo ◽  
Developmental Competence ◽  
Success Rates ◽  
Developmental Potential ◽  
Mtdna Sequence

Abstract Study question Does cumulus cell mtDNA content correlate with oocyte developmental potential in the bovine model? Summary answer The relative amount of mtDNA content did not vary significantly in oocytes showing different developmental outcomes following IVF What is known already Cumulus cells are closely connected to the oocyte through transzonal projections, serving essential metabolic functions during folliculogenesis. These oocyte-supporting cells are removed and discarded prior to ICSI, thereby constituting an interesting biological material on which to perform molecular analysis aimed to predict oocyte developmental competence. Previous studies have positively associated oocytés mtDNA content with developmental potential in both animal models and women. However, it remains debatable whether mtDNA content in cumulus cells could be used as a proxy to infer oocyte developmental potential. Study design, size, duration Bovine cumulus cells were allocated into three groups according to the developmental potential of the oocyte: 1) oocytes developing to blastocysts following IVF (Bl+Cl+), 2) oocytes cleaving following IVF but arresting their development prior to the blastocyst stage (Bl-Cl+), and 3) oocytes not cleaving following IVF (Bl-Cl-). Relative mtDNA content was analysed in 40 samples/group, each composed by the cumulus cells from one cumulus-oocyte complex (COC). Participants/materials, setting, methods Bovine cumulus-oocyte complexes were obtained from slaughtered cattle and individually matured in vitro (IVM). Following IVM, cumulus cells were removed by hyaluronidase treatment, pelleted, snap frozen in liquid nitrogen and stored at –80 ºC until analysis. Cumulus-free oocytes were fertilized and cultured in vitro individually and development was recorded for each oocyte. Relative mtDNA abundance was determined by qPCR, amplifying a mtDNA sequence (COX1) and a chromosomal sequence (PPIA). Statistical differences were tested by ANOVA. Main results and the role of chance Relative mtDNA abundance did not differ significantly (ANOVA p &gt; 0.05) between the three groups exhibiting different developmental potential (1±0.06 vs. 1.19±0.05 vs. 1.11±0.05, for Bl+Cl+ vs. Bl-Cl+ vs. Bl-Cl-, mean±s.e.m.). Limitations, reasons for caution Experiments were conducted in the bovine model. Although bovine folliculogenesis, monoovulatory ovulation and early embryo development exhibit considerable similarities with that of humans, caution should be taken when extrapolating these data to humans. Wider implications of the findings: The use of molecular markers for oocyte developmental potential in cumulus cells could be used to enhance success rates following single-embryo transfer. Unfortunately, mtDNA in cumulus cells was not found to be a good proxy for oocyte quality. Trial registration number Not applicable

P–431 Human oocytes in-vitro maturation efficacy from infancy to adulthood – is there an optimal age?

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
G Karavani ◽  
P Wasserzug-Pash ◽  
T Mordechai-Daniel ◽  
M Klutstein ◽  
T Imbar
Keyword(s):  
Fertility Preservation ◽  
In Vitro Maturation ◽  
Ovarian Tissue ◽  
Age Groups ◽  
Ovarian Tissue Cryopreservation ◽  
Success Rates ◽  
Human Oocytes ◽  
Tertiary Center ◽  
Significant Difference

Abstract Study question Does human oocytes in-vitro maturation (IVM) effectiveness change throughout childhood, adolescence and adulthood in girls and women undergoing fertility preservation via ovarian tissue cryopreservation (OTC) prior to chemo-radiotherapy exposure? Summary answer The optimal age for IVM is from menarche to 25 years, while pre-menarche girls and women older than 30 years have extremely low maturation rates. What is known already In vitro maturation of oocytes from antral follicles seen during tissue harvesting is a fertility preservation technique with potential advantages over OTC, as mature frozen and later thawed oocyte used for fertilization poses decreased risk of malignant cells re-seeding, as compared to ovarian tissue implantation. We previously demonstrated that IVM performed following OTC in fertility preservation patients, even in pre-menarche girls, yields a fair amount of oocytes available for IVM and freezing for future use. Study design, size, duration A retrospective cohort study, evaluating IVM outcomes in chemotherapy naïve patients referred for fertility preservation by OTC that had oocyte collected from the medium with attempted IVM between 2003 and 2020 in a university affiliated tertiary center. Participants/materials, setting, methods A total of 133 chemotherapy naïve patients aged 1–35 years with attempted IVM were included in the study. The primary outcome was IVM rate in the different age groups – pre-menarche (1–5 years and ≥6 years), post-menarche (menarche–17 years), young adults (18–24 years) and adults (25–29 and 30–35 years). Comparison between paired groups for significant difference in the IVM rate parameter was done using the Tukey’s Studentized Range (HSD) Test. Main results and the role of chance A gradual increase in mean IVM rate was demonstrated in the age groups over 1 to 25 years (4.6% (1–5 years), 23.8% (6 years to menarche) and 28.4% (menarche to 17 years), with a peak of 38.3% in the 18–24 years group, followed by a decrease in the 25–29 years group (19.3%), down to a very low IVM rate (8.9%) in the 30–35 years group. A significant difference in IVM rates was noted between the age extremes – the very young (1–5 years) and the oldest (30–35 years) groups, as compared with the 18–24-year group (p &lt; 0.001). Number of oocytes matured, percent of patients with matured oocytes and overall maturation rate differed significantly (p &lt; 0.001). Limitations, reasons for caution Data regarding ovarian reserve evaluation was not available for most of the patients, due to our pre-op OTC procedures protocol. None of our patients have used their frozen in-vitro matured oocytes, as such further implications of age on in-vitro matured oocytes quality and implantation potential has yet to be evaluated. Wider implications of the findings: Our finding of extremely low success rates in those very young (under 6 years) and older (≥30 years) patients suggest that IVM of oocyte retrieved during OTC prior to chemotherapy should not be attempted in these age group. Trial registration number N/A

scholarly journals Effects of BMP15 and GDF9 on Ovine Oocytes in an In Vitro Maturation System

2021 ◽  
Author(s):  
◽  
Aanchal Singh
Keyword(s):  
Cell Death ◽  
Litter Size ◽  
In Vitro Maturation ◽  
Cumulus Cell ◽  
Oocyte Quality ◽  
Mature Oocyte ◽  
High Ratio ◽  
High Fecundity ◽  
Species Specific

<p>Oocyte developmental competency is the intrinsic measure of oocyte quality and the capacity for a mature oocyte to support the early stages of embryo development and implantation. Oocyte-secreted factors (OSFs), such as growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15), play a pivotal role in regulating the synchrony of various complex maturation events within the cumulus-oocyte complex (COC) through the induction of paracrine and endocrine signalling. These proteins act synergistically to influence the proliferation and differentiation of granulosa cells (GCs), cumulus cell (CC) expansion, promote survival, ovulation, the attainment of developmental competency and fertility. Species-specific ratios suggest that poly-ovulatory mammals have increased fecundity due to high ratios of GDF9:BMP15, which is directly reflected in their large litter size. Interestingly, it has also been found that higher ratios of GDF9:BMP15 also increased blastocyst rate in sheep implying that these embryos develop from oocytes that are more developmentally competent.  In this study, I investigated the hypothesis that supplementing a commercial in vitro maturation (IVM) system with a high ratio of GDF9:BMP15 would increase the developmental competency sheep oocytes; a species with low-moderate litter size. To test this hypothesis, ovine oocytes were matured in a biphasic IVM system containing GDF9 and BMP15 at three divergent ratios (1:6, 1:1, 6:1). The results herein show that the 6:1 ratio resulted in higher levels of reagent transfer to the ovine oocyte through gap junctions (GJs) after 24 hours of incubation. Similarly, it was also observed that at the higher ratio, glutathione (GSH) levels were higher at 7.5 hours of incubation. The high GDF9:BMP15 ratio also facilitated the increased consumption of pyruvate by the COC consistently throughout the culture period. Importantly, the high GDF9:BMP15 ratio showed higher expression of the gene that encodes GJ (CX43) at 24 hours relative to the control. It was also demonstrated through decreased apoptotic factor (BAX:BCL2) ratios, that the addition of OSFs, regardless of ratio, protected against cell death. In summary, this study provides novel results that support the notion that a high GDF9:BMP15 ratio improves oocyte quality by delaying the timing of meiotic resumption. This subsequently improves the transport of key metabolites and antioxidants to protect against oxidative stress and cell death and aid in the completion of maturation, ultimately resulting in the increased developmental competency observed in high fecundity poly-ovulatory species.</p>

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.

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