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.

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 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.

scholarly journals Embryotropic actions of follistatin: paracrine and autocrine mediators of oocyte competence and embryo developmental progression

2014 ◽  
Vol 26 (1) ◽  
pp. 37 ◽  
Author(s):  
Sandeep K. Rajput ◽  
KyungBon Lee ◽  
Guo Zhenhua ◽  
Liu Di ◽  
Joseph K. Folger ◽  
...  
Keyword(s):  
Somatic Cell ◽  
Molecular Mechanisms ◽  
Assisted Reproductive Technologies ◽  
Reproductive Technologies ◽  
Developmental Competence ◽  
Family Impact ◽  
Oocyte Growth ◽  
Oocyte Competence ◽  
Developmental Progression

Despite several decades since the birth of the first test tube baby and the first calf derived from an in vitro-fertilised embryo, the efficiency of assisted reproductive technologies remains less than ideal. Poor oocyte competence is a major factor limiting the efficiency of in vitro embryo production. Developmental competence obtained during oocyte growth and maturation establishes the foundation for successful fertilisation and preimplantation embryonic development. Regulation of molecular and cellular events during fertilisation and embryo development is mediated, in part, by oocyte-derived factors acquired during oocyte growth and maturation and programmed by factors of follicular somatic cell origin. The available evidence supports an important intrinsic role for oocyte-derived follistatin and JY-1 proteins in mediating embryo developmental progression after fertilisation, and suggests that the paracrine and autocrine actions of oocyte-derived growth differentiation factor 9, bone morphogenetic protein 15 and follicular somatic cell-derived members of the fibroblast growth factor family impact oocyte competence and subsequent embryo developmental progression after fertilisation. An increased understanding of the molecular mechanisms mediating oocyte competence and stage-specific developmental events during early embryogenesis is crucial for further improvements in assisted reproductive technologies.

scholarly journals Cyclophosphamide Exposure Causes Long-Term Detrimental Effect of Oocytes Developmental Competence Through Affecting the Epigenetic Modification and Maternal Factors’ Transcription During Oocyte Growth

2021 ◽  
Vol 9 ◽  
Author(s):  
Weijie Yang ◽  
Yerong Ma ◽  
Jiamin Jin ◽  
Peipei Ren ◽  
Hanjing Zhou ◽  
...  
Keyword(s):  
Dna Damage ◽  
Culture Media ◽  
Epigenetic Modification ◽  
Primordial Follicle ◽  
Oocyte Quality ◽  
Mature Oocyte ◽  
Developmental Competence ◽  
Oocyte Growth ◽  
Primordial Follicles

Cyclophosphamide (CTX) is widely used in various cancer therapies and in immunosuppression, and patients can still have babies after CTX chemotherapy. CTX directly causes primordial follicle loss with overactivation and DNA damage-induced apoptosis. Previous studies have shown that maternal exposure to CTX before conception increases the incidence of birth abnormalities and alters the methylation of genes in the oocytes of offspring. Mice were treated with a single dose of CTX (100 mg/kg) at post-natal day 21 and sacrificed 47 days later when primordial follicles surviving chemotherapy developed to the antral stage. Acute DNA damage and acceleration of the activation of primordial follicles after CTX treatment were repaired within several days, but the remaining follicle numbers remarkably decrease. Although partial surviving primordial follicle were developed to mature oocyte, oocyte quality hemostasis was impaired exhibiting aberrant meiosis progression, abnormal spindle and aneuploidy, mitochondrial dysfunction and increased endoplasmic reticulum stress. Thereafter, embryo development competency significantly decreased with fewer blastocyst formation after CTX exposure. CTX treatment resulted in alteration of DNA methylations and histone modifications in fully grown GV oocytes. Single-cell RNA-seq revealed CTX treatment suppressed multiple maternal genes’ transcription including many methyltransferases and maternal factor YAP1, which probably accounts for low quality of CTX-repaired oocyte. In vitro addition of lysophosphatidic acid (LPA) to embryo culture media to promote YAP1 nuclear localization improved CTX-repaired embryo developmental competence. This study provides evidence for the consistent toxic effect of CTX exposure during follicle development, and provide a new mechanism and new insights into future clinical interventions for fertility preservation.

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 Increased WIP1 Expression With Aging Suppresses the Capacity of Oocytes to Respond to and Repair DNA Damage

2021 ◽  
Vol 9 ◽  
Author(s):  
Jiyeon Leem ◽  
Guang-Yu Bai ◽  
Jae-Sung Kim ◽  
Jeong Su Oh
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Oocyte Quality ◽  
Developmental Competence ◽  
Repair Capacity ◽  
Dna Repair Capacity ◽  
Age Related ◽  
Postovulatory Aging

If fertilization does not occur for a prolonged time after ovulation, oocytes undergo a time-dependent deterioration in quality in vivo and in vitro, referred to as postovulatory aging. The DNA damage response is thought to decline with aging, but little is known about how mammalian oocytes respond to the DNA damage during in vitro postovulatory aging. Here we show that increased WIP1 during in vitro postovulatory aging suppresses the capacity of oocytes to respond to and repair DNA damage. During in vitro aging, oocytes progressively lost their capacity to respond to DNA double-strand breaks, which corresponded with an increase in WIP1 expression. Increased WIP1 impaired the amplification of γ-H2AX signaling, which reduced the DNA repair capacity. WIP1 inhibition restored the DNA repair capacity, which prevented deterioration in oocyte quality and improved the fertilization and developmental competence of aged oocytes. Importantly, WIP1 was also found to be high in maternally aged oocytes, and WIP1 inhibition enhanced the DNA repair capacity of maternally aged oocytes. Therefore, our results demonstrate that increased WIP1 is responsible for the age-related decline in DNA repair capacity in oocytes, and WIP1 inhibition could restore DNA repair capacity in aged oocytes.

scholarly journals Interplay between Cellular and Molecular Mechanisms Underlying Inflammatory Bowel Diseases Development—A Focus on Ulcerative Colitis

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1647
Author(s):  
Iuliana Samoilă ◽  
Sorina Dinescu ◽  
Marieta Costache
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Diseases ◽  
Molecular Mechanisms ◽  
Inflammasome Activation ◽  
Intestinal Epithelial ◽  
Aberrant Expression ◽  
Unfolded Protein ◽  
Pyrin Domain ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Inflammatory bowel diseases (IBD) are defined by the continuous inflammation of the gastrointestinal tract. During inflammation, the number of pathogens in the intestinal epithelium increases, leading to inflammasome assembly. Inflammasome activation is meant to protect the intestinal epithelial barrier from further damage by maintaining homeostasis. Although its purpose is to protect the cells, excessive nucleotide-binding oligomerization domain-like receptor and pyrin domain-containing protein 3 (NLRP3) inflammasome assembly is responsible for the synthesis of a high number of pro-inflammatory cytokines. The activation of two crucial pathways, autophagy process, and unfolded protein response, is initiated for restoring homeostasis. Aberrant expression of miRNAs and lncRNAs also interfere with the pathogenic mechanisms of IBD, as these non-coding transcripts play key roles in regulation of biological processes, such as inflammation and immunity. This review thoroughly describes the cellular and molecular mechanism that trigger and perpetuate inflammation in ulcerative colitis (UC) patients.

scholarly journals The Function of Cumulus Cells in Oocyte Growth and Maturation and in Subsequent Ovulation and Fertilization

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2292
Author(s):  
Bongkoch Turathum ◽  
Er-Meng Gao ◽  
Ri-Cheng Chian
Keyword(s):  
Granulosa Cells ◽  
Follicular Development ◽  
Cumulus Cells ◽  
Oocyte Quality ◽  
Early Embryo ◽  
Developmental Competence ◽  
Meiotic Maturation ◽  
Supporting Cells ◽  
Oocyte Growth ◽  
Oocyte Meiotic Maturation

Cumulus cells (CCs) originating from undifferentiated granulosa cells (GCs) differentiate in mural granulosa cells (MGCs) and CCs during antrum formation in the follicle by the distribution of location. CCs are supporting cells of the oocyte that protect the oocyte from the microenvironment, which helps oocyte growth and maturation in the follicles. Bi-directional communications between an oocyte and CCs are necessary for the oocyte for the acquisition of maturation and early embryonic developmental competence following fertilization. Follicle-stimulation hormone (FSH) and luteinizing hormone (LH) surges lead to the synthesis of an extracellular matrix in CCs, and CCs undergo expansion to assist meiotic resumption of the oocyte. The function of CCs is involved in the completion of oocyte meiotic maturation and ovulation, fertilization, and subsequent early embryo development. Therefore, understanding the function of CCs during follicular development may be helpful for predicting oocyte quality and subsequent embryonic development competence, as well as pregnancy outcomes in the field of reproductive medicine and assisted reproductive technology (ART) for infertility treatment.

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
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