scholarly journals Female Aging Alters Expression of Human Cumulus Cells Genes that Are Essential for Oocyte Quality

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Tamadir Al-Edani ◽  
Said Assou ◽  
Alice Ferrières ◽  
Sophie Bringer Deutsch ◽  
Anna Gala ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Age Groups ◽  
Cumulus Cells ◽  
Bioinformatic Analysis ◽  
Oocyte Quality ◽  
Human Reproduction ◽  
Transcriptome Profile ◽  
Developmental Potential ◽  
Female Aging ◽  
Angiogenic Genes

Impact of female aging is an important issue in human reproduction. There was a need for an extensive analysis of age impact on transcriptome profile of cumulus cells (CCs) to link oocyte quality and developmental potential with patient’s age. CCs from patients of three age groups were analyzed individually using microarrays. RT-qPCR validation was performed on independent CC cohorts. We focused here on pathways affected by aging in CCs that may explain the decline of oocyte quality with age. In CCs collected from patients >37 years, angiogenic genes includingANGPTL4,LEPR,TGFBR3, andFGF2were significantly overexpressed compared to patients of the two younger groups. In contrast genes implicated in TGF-βsignaling pathway such asAMH,TGFB1, inhibin, and activin receptor were underexpressed. CCs from patients whose ages are between 31 and 36 years showed an overexpression of genes related to insulin signaling pathway such asIGFBP3,PIK3R1, andIGFBP5. A bioinformatic analysis was performed to identify the microRNAs that are potential regulators of the differentially expressed genes of the study. It revealed that the pathways impacted by age were potential targets of specific miRNAs previously identified in our CCs small RNAs sequencing.

Maternal age affects oocyte developmental potential at both ends of the age spectrum

2019 ◽  
Vol 31 (1) ◽  
pp. 1 ◽  
Author(s):  
Rebecca L. Krisher
Keyword(s):  
Metabolic Pathways ◽  
Maternal Age ◽  
Age Groups ◽  
Cumulus Cells ◽  
Oocyte Quality ◽  
Developmental Competence ◽  
Cellular Mechanisms ◽  
Developmental Potential ◽  
Oocyte Developmental Competence ◽  
Maternal Mrnas

Maternal age has a significant effect on oocyte developmental competence. Overall, evidence suggests that oocytes from both prepubertal females and reproductively aged females are inherently less competent. Reduced oocyte quality in both age groups is problematic for human medicine and agriculture. Some of the cellular mechanisms implicated in poor oocyte quality associated with maternal age are mitochondrial function and location, reduction of oxygen radicals, balance of metabolic pathways, regulation of maternal mRNAs and appropriate communication between the oocyte and cumulus cells. However, additional knowledge must be gained about the deficiencies present in prepubertal and reproductively aged oocytes that result in poor developmental potential before significant improvement can be achieved. This review discusses the evidence currently available regarding oocyte quality at both ends of the maternal age spectrum, what we know, or hypothesise, about the mechanisms involved and current thoughts regarding potential treatment for improvement.

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 > 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

Equine maternal aging affects oocyte lipid content, metabolic function and developmental potential

Reproduction ◽  
2021 ◽  
Vol 161 (4) ◽  
pp. 399-409
Author(s):  
Giovana D Catandi ◽  
Yusra M Obeidat ◽  
Corey D Broeckling ◽  
Thomas W Chen ◽  
Adam J Chicco ◽  
...  
Keyword(s):  
Relative Abundance ◽  
Mammalian Species ◽  
Age Groups ◽  
Cumulus Cells ◽  
Developmental Competence ◽  
Metabolic Function ◽  
Mtdna Copy Number ◽  
Developmental Potential ◽  
Maternal Aging

Advanced maternal age is associated with a decline in fertility and oocyte quality. We used novel metabolic microsensors to assess effects of mare age on single oocyte and embryo metabolic function, which has not yet been similarly investigated in mammalian species. We hypothesized that equine maternal aging affects the metabolic function of oocytes and in vitro-produced early embryos, oocyte mitochondrial DNA (mtDNA) copy number, and relative abundance of metabolites involved in energy metabolism in oocytes and cumulus cells. Samples were collected from preovulatory follicles from young (≤14 years) and old (≥20 years) mares. Relative abundance of metabolites in metaphase II oocytes (MII) and their respective cumulus cells, detected by liquid and gas chromatography coupled to mass spectrometry, revealed that free fatty acids were less abundant in oocytes and more abundant in cumulus cells from old vs young mares. Quantification of aerobic and anaerobic metabolism, respectively measured as oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) in a microchamber containing oxygen and pH microsensors, demonstrated reduced metabolic function and capacity in oocytes and day-2 embryos originating from oocytes of old when compared to young mares. In mature oocytes, mtDNA was quantified by real-time PCR and was not different between the age groups and not indicative of mitochondrial function. Significantly more sperm-injected oocytes from young than old mares resulted in blastocysts. Our results demonstrate a decline in oocyte and embryo metabolic activity that potentially contributes to the impaired developmental competence and fertility in aged females.

065. THE MAMMALIAN OOCYTE: FROM BENCH TO CLINIC

2009 ◽  
Vol 21 (9) ◽  
pp. 18
Author(s):  
R. B. Gilchrist
Keyword(s):  
Somatic Cells ◽  
Cumulus Cells ◽  
Reproductive Technologies ◽  
Oocyte Quality ◽  
Female Fertility ◽  
Widespread Application ◽  
Developmental Potential ◽  
Mammalian Oocyte ◽  
Wide Range

The mature mammalian oocyte is the central link between generations. It is not only responsible for the transfer of the female genome between generations, but also largely determines embryo and early fetal developmental potential. For any female, oocytes are in limited supply and are easily damaged, such that the availability of high quality or developmentally competent oocytes is a fundamental rate-limiting factor in female fertility. This is particularly relevant in Australian society today with the steadily rising age to first conception which adversely affects oocyte quality and female fertility. Yet despite years of research and clinical IVF we still have a poor understanding of the molecular and cellular processes that control oocyte quality. It is clear that oocytes acquire developmental competence in the ovarian follicle. The acquisition of competence necessitates communication between the oocyte and maternal systems, a process which endows developmental potential as the oocyte grows and matures inside the follicle. At the cellular level this is achieved by bi-directional communication between oocytes and their companion somatic cells [1]. Over the past 10 years my laboratory has focused heavily on the nature of these oocyte-somatic communication axes and their impact on oocyte quality. Over this period, our work and that of others has shaped a new paradigm in ovarian biology, which is that the oocyte is not passive in the follicle, but rather that it actively directs the differentiation of its neighbouring somatic cells into cumulus cells through the secretion of GDF9 and BMP15 growth factors [2]. In doing so, oocytes dictate the function of their neighboring cumulus cells, directing them to perform functions needed for the appropriate growth and development of the oocyte. For example, cumulus cells supply oocytes with an array of nutrients, substrates and regulatory molecules such as cAMP, many directly through gap-junctions. These communication axes establish and maintain an elaborate and intricate local oocyte-cumulus auto regulatory loop that is required to enable post-fertilisation development. A clear clinical application of this new knowledge is in Artificial Reproductive Technologies, in particular oocyte in vitro maturation (IVM) [3]. IVM biotechnologies have the capacity to capture the vast supply of oocytes in the mammalian ovary and generate mature oocytes in vitro. Generating offspring using IVM is already a clinically and commercially viable biotechnology in livestock breeding programs, particularly in cattle. IVM is a particularly attractive technology for the treatment of human infertility, as it removes the need for expensive and potentially harmful ovarian hyperstimulation protocols used in clinical IVF. However, widespread application of IVM in humans requires an increase in efficiency and further examination of safety of the technology. Recent work from my laboratory has increased IVM success rates in animals by using GDF9 and BMP15 in IVM [2, 3] and by developing a new system of “Induced-IVM” that more closely resembles the mechanisms of oocyte maturation in vivo. Most recently, the latter approach has led to substantial increases in embryo yield and pregnancy outcomes to levels equivalent to hormone-stimulated IVF [4]. The next challenge is to adapt these new approaches to clinical/field conditions to provide new opportunities for infertile women and for the development of a wide range of reproductive biotechnologies.

scholarly journals Female ageing affects the DNA repair capacity of oocytes in IVF using a controlled model of sperm DNA damage in mice

2020 ◽  
Vol 35 (3) ◽  
pp. 529-544 ◽  
Author(s):  
F Horta ◽  
S Catt ◽  
P Ramachandran ◽  
B Vollenhoven ◽  
P Temple-Smith
Keyword(s):  
Gene Expression ◽  
Dna Damage ◽  
Dna Repair ◽  
Age Groups ◽  
Oocyte Quality ◽  
Repair Capacity ◽  
Sperm Dna Damage ◽  
Dna Repair Capacity ◽  
Sperm Dna ◽  
Damage Response

Abstract STUDY QUESTION Does female ageing have a negative effect on the DNA repair capacity of oocytes fertilised by spermatozoa with controlled levels of DNA damage? SUMMARY ANSWER Compared to oocytes from younger females, oocytes from older females have a reduced capacity to repair damaged DNA introduced by spermatozoa. WHAT IS KNOWN ALREADY The reproductive lifespan in women declines with age predominantly due to poor oocyte quality. This leads to decreased reproductive outcomes for older women undergoing assisted reproductive technology (ART) treatments, compared to young women. Ageing and oocyte quality have been clearly associated with aneuploidy, but the range of factors that influence this change in oocyte quality with age remains unclear. The DNA repair activity prior to embryonic genomic activation is considered to be of maternal origin, with maternal transcripts and proteins controlling DNA integrity. With increasing maternal age, the number of mRNAs stored in oocytes decreases. This could result in diminished efficiency of DNA repair and/or negative effects on embryo development, especially in the presence of DNA damage. STUDY DESIGN, SIZE, DURATION Oocytes from two age groups of 30 super-ovulated female mice (young: 5–8 weeks old, n = 15; old: 42–45 weeks old, n = 15) were inseminated with sperm from five males with three different controlled DNA damage levels; control: ≤10%, 1 Gray (Gy): 11–30%, and 30 Gy: >30%. Inseminated oocytes (young: 125, old: 78) were assessed for the formation of zygotes (per oocyte) and blastocysts (per zygote). Five replicates of five germinal vesicles (GVs) and five MII oocytes from each age group were analysed for gene expression. The DNA damage response (DDR) was assessed in a minimum of three IVF replicates in control and 1 Gy zygotes and two-cell embryos using γH2AX labelling. PARTICIPANTS/MATERIALS, SETTING, METHODS Swim-up sperm samples from the cauda epididymidis of C57BL6 mice were divided into control (no irradiation) and 1- and 30-Gy groups. Treated spermatozoa were irradiated at 1 and 30 Gy, respectively, using a linear accelerator Varian 21iX. Following irradiation, samples were used for DNA damage assessment (Halomax) and for insemination. Presumed zygotes were cultured in a time-lapse incubator (MIRI, ESCO). Gene expression of 91 DNA repair genes was assessed using the Fluidigm Biomark HD system. The DNA damage response in zygotes (6–8 h post-fertilisation) and two-cell embryos (22–24 h post-fertilisation) was assessed by immunocytochemical analysis of γH2AX using confocal microscopy (Olympus FV1200) and 3D volumetric analysis using IMARIS software. MAIN RESULTS AND THE ROLE OF CHANCE The average sperm DNA damage for the three groups was statistically different (control: 6.1%, 1 Gy: 16.1%, 30 Gy: 53.1%, P < 0.0001), but there were no significant differences in fertilisation rates after IVF within or between the two age groups [(young; control: 86.79%, 1 Gy: 82.75%, 30 Gy: 76.74%) (old; control: 93.1%, 1 Gy: 70.37%, 30 Gy: 68.18%) Fisher’s exact]. However, blastocyst rates were significantly different (P < 0.0001) among the groups [(young; control: 86.95%, 1 Gy: 33.33%, 30 Gy: 0.0%) (old; control: 70.37%, 1 Gy: 0.0%, 30 Gy: 0.0%)]. Between the age groups, 1-Gy samples showed a significant decrease in the blastocyst rate in old females compared to young females (P = 0.0166). Gene expression analysis revealed a decrease in relative expression of 21 DNA repair genes in old GV oocytes compared to young GV oocytes (P < 0.05), and similarly, old MII oocytes showed 23 genes with reduced expression compared to young MII oocytes (P < 0.05). The number of genes with decreased expression in older GV and MII oocytes significantly affected pathways such as double strand break (GV: 5; MII: 6), nucleotide excision repair (GV: 8; MII: 5) and DNA damage response (GV: 4; MII: 8). There was a decreased DDR in zygotes and in two-cell embryos from old females compared to young regardless of sperm treatment (P < 0.05). The decrease in DNA repair gene expression of oocytes and decreased DDR in embryos derived from older females suggests that ageing results in a diminished DNA repair capacity. LARGE-SCALE DATA N/A LIMITATIONS, REASONS FOR CAUTION Ionising radiation was used only for experimental purposes, aiming at controlled levels of sperm DNA damage; however, it can also damage spermatozoa proteins. The female age groups selected in mice were intended to model effects in young and old women, but clinical studies are required to demonstrate a similar effect. WIDER IMPLICATIONS OF THE FINDINGS Fertilisation can occur with sperm populations with medium and high DNA damage, but subsequent embryo growth is affected to a greater extent with aging females, supporting the theory that oocyte DNA repair capacity decreases with age. Assessment of the oocyte DNA repair capacity may be a useful diagnostic tool for infertile couples. STUDY FUNDING/COMPETING INTEREST(S) Funded by the Education Program in Reproduction and Development, Department of Obstetrics and Gynaecology, Monash University. None of the authors has any conflict of interest to report.

scholarly journals DEVELOPMENT OF DIAMONOLOGICAL COMPETENCE OF FUTURE PRIMARY SCHOOL TEACHERS IN THE PROCESS OF PROFESSIONAL TRAINING

2021 ◽  
Vol 1 ◽  
pp. 395-405
Author(s):  
Iryna Lapshyna ◽  
Lyudmila Lyubchak ◽  
Nataliia Franchuk ◽  
Alla Vasylyuk ◽  
Nadiia Komarivska
Keyword(s):  
Primary School ◽  
Personal Growth ◽  
Professional Training ◽  
Large Scale ◽  
Group Discussion ◽  
Age Groups ◽  
Educational Process ◽  
School Teachers ◽  
Developmental Potential ◽  
Primary School Teachers

The implementation of active forms and methods of group interaction in the educational process is recognized as a perspective means of developing future teachers’ communication. From the authors’ standpoint, it is necessary to re-evaluate the developmental potential of such specific methods as discussion methods (group discussion, analysis and commentary of situations); play methods (role-, director-, and counterplays) and play psychotherapy, trainings of interpersonal sensitivity, personal growth, techniques of non-verbal interaction and others. The topicality of such re-evaluation is caused not only by the reform processes in the education system of Ukraine, but also by the modern challenge to the whole system of world education - the need for large-scale implementation of distance forms of the educational process organization in connection with the pandemic situation. The survey of future primary school teachers conducted by the authors, indicates a low readiness of modern teachers to use active teaching methods for training schoolchildren of different age groups, to organize speech interaction with students based on emotional involvement in work, critical re-evaluating of self-position, frank and reasoned expression of thoughts and feelings. In this regard, the issues of the development of diamonological competence of the higher education institutions students acquire additional relevance in the pedagogical discussion. 

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