RAB7 activity is required for the regulation of mitophagy in oocyte meiosis and oocyte quality control during ovarian aging

Autophagy ◽  
2021 ◽  
pp. 1-18
Author(s):  
Xin Jin ◽  
Kehan Wang ◽  
Lu Wang ◽  
Wenwen Liu ◽  
Chi Zhang ◽  
...  
Keyword(s):  
Quality Control ◽  
Oocyte Quality ◽  
Ovarian Aging ◽  
Oocyte Meiosis

scholarly journals Establishment of a Mouse Model of Premature Ovarian Failure Using Consecutive Superovulation

2018 ◽  
Vol 51 (5) ◽  
pp. 2341-2358 ◽  
Author(s):  
Xiaowei Nie ◽  
Youjin Dai ◽  
Yuan Zheng ◽  
Dan Bao ◽  
Qin Chen ◽  
...  
Keyword(s):  
Mouse Model ◽  
Premature Ovarian Failure ◽  
Cell Apoptosis ◽  
Quantitative Polymerase Chain Reaction ◽  
Oocyte Quality ◽  
Ovarian Failure ◽  
Control Group ◽  
Mrna Levels ◽  
Primordial Follicles ◽  
Ovarian Aging

Background/Aims: This study investigated the effect of consecutive superovulation on the ovaries and established a premature ovarian failure (POF) model in mice. Methods: The mouse POF model was induced by 5-15 consecutive superovulation treatments with pregnant mare serum gonadotropin (PMSG), human chorionic gonadotropin (HCG) and prostaglandin F2α (PGF2α). Normal adult mice were compared with mice displaying natural ovarian aging. The following serum biochemical parameters were measured: including follicle-stimulating hormone (FSH), luteinizing hormone (LH), progesterone (P), estradiol (E2), inhibin B (INH B), malondialdehyde (MDA), total superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels. Follicles were counted using H&E staining. Levels of 8-hydroxyguanosine (8-OhdG), 4-hydroxynonenal (4-HNE), nitrotyrosine (NTY), anti-Mullerian hormone (AMH) and CDKN2A/ p16 (p16) were detected using immunohistochemical staining. Reactive oxygen species (ROS) levels were measured using dihydroethidium (DHE) staining. Cell apoptosis was detected using an in situ TUNEL fluorescence staining assay. Levels of proteins involved in ROS-related pathways and the p16 protein were detected using Western blotting. Sod1, Sod2 and Sod3 mRNA levels were detected using quantitative polymerase chain reaction (Q-PCR). Oocyte quality was evaluated using in vitro fertilization (IVF) and zygote culture. Results: Consecutive superovulation groups presented lower P, E2, SOD, GSH-Px and INH B levels, significantly higher FSH, LH, MDA and ROS levels, and significantly fewer primordial follicles compared with the control group. Consecutive superovulation groups presented significantly increased levels of Sod2, 8-OhdG, 4-HNE, NTY, significantly increased levels of the SIRT1 and FOXO1 proteins, significantly increased levels of the senescence-associated protein p16, as well as decreased AMH, Sod1 and Sod3 levels and increased granulosa cell apoptosis compared with the control group. Conclusion: Consecutive superovulation significantly decreased ovarian function and oocyte quality and increased oxidative stress and apoptosis in the ovary via a mechanism involving the p16 and SIRT1/FOXO1 signaling pathways. These findings suggest that consecutive superovulation may be used to establish a mouse model of ovarian aging.

scholarly journals Drosophila p53 isoforms have overlapping and distinct functions in germline genome integrity and oocyte quality control

eLife ◽  
2022 ◽  
Vol 11 ◽  
Author(s):  
Ananya Chakravarti ◽  
Heshani N Thirimanne ◽  
Savanna Brown ◽  
Brian R Calvi
Keyword(s):  
Quality Control ◽  
Family Members ◽  
P53 Gene ◽  
Genotoxic Stress ◽  
Oocyte Quality ◽  
Protein Isoforms ◽  
Dna Breaks ◽  
P53 Family ◽  
Dna Lesion ◽  
P53 Isoforms

p53 gene family members in humans and other organisms encode a large number of protein isoforms whose functions are largely undefined. Using Drosophila as a model, we find that a p53B isoform is expressed predominantly in the germline where it colocalizes with p53A into subnuclear bodies. It is only p53A, however, that mediates the apoptotic response to ionizing radiation in the germline and soma. In contrast, p53A and p53B are both required for the normal repair of meiotic DNA breaks, an activity that is more crucial when meiotic recombination is defective. We find that in oocytes with persistent DNA breaks p53A is also required to activate a meiotic pachytene checkpoint. Our findings indicate that Drosophila p53 isoforms have DNA lesion and cell type-specific functions, with parallels to the functions of mammalian p53 family members in the genotoxic stress response and oocyte quality control.

scholarly journals BRCA-related ATM-mediated DNA double-strand break repair and ovarian aging

2019 ◽  
Vol 26 (1) ◽  
pp. 43-57 ◽  
Author(s):  
Volkan Turan ◽  
Kutluk Oktay
Keyword(s):  
Clinical Evidence ◽  
Strand Break ◽  
Oocyte Quality ◽  
Repair Pathway ◽  
Dsb Repair ◽  
Ovarian Aging ◽  
Age Related ◽  
Dna Double Strand Break ◽  
Targeted Treatments ◽  
Oocyte Aging

Abstract BACKGROUND Oocyte aging has significant clinical consequences, and yet no treatment exists to address the age-related decline in oocyte quality. The lack of progress in the treatment of oocyte aging is due to the fact that the underlying molecular mechanisms are not sufficiently understood. BRCA1 and 2 are involved in homologous DNA recombination and play essential roles in ataxia telangiectasia mutated (ATM)-mediated DNA double-strand break (DSB) repair. A growing body of laboratory, translational and clinical evidence has emerged within the past decade indicating a role for BRCA function and ATM-mediated DNA DSB repair in ovarian aging. OBJECTIVE AND RATIONALE Although there are several competing or complementary theories, given the growing evidence tying BRCA function and ATM-mediated DNA DSB repair mechanisms in general to ovarian aging, we performed this review encompassing basic, translational and clinical work to assess the current state of knowledge on the topic. A clear understanding of the mechanisms underlying oocyte aging may result in targeted treatments to preserve ovarian reserve and improve oocyte quality. SEARCH METHODS We searched for published articles in the PubMed database containing key words, BRCA, BRCA1, BRCA2, Mutations, Fertility, Ovarian Reserve, Infertility, Mechanisms of Ovarian Aging, Oocyte or Oocyte DNA Repair, in the English-language literature until May 2019. We did not include abstracts or conference proceedings, with the exception of our own. OUTCOMES Laboratory studies provided robust and reproducible evidence that BRCA1 function and ATM-mediated DNA DSB repair, in general, weakens with age in oocytes of multiple species including human. In both women with BRCA mutations and BRCA-mutant mice, primordial follicle numbers are reduced and there is accelerated accumulation of DNA DSBs in oocytes. In general, women with BRCA1 mutations have lower ovarian reserves and experience earlier menopause. Laboratory evidence also supports critical role for BRCA1 and other ATM-mediated DNA DSB repair pathway members in meiotic function. When laboratory, translational and clinical evidence is considered together, BRCA-related ATM-mediated DNA DSB repair function emerges as a likely regulator of ovarian aging. Moreover, DNA damage and repair appear to be key features in chemotherapy-induced ovarian aging. WIDER IMPLICATIONS The existing data suggest that the BRCA-related ATM-mediated DNA repair pathway is a strong candidate to be a regulator of oocyte aging, and the age-related decline of this pathway likely impairs oocyte health. This knowledge may create an opportunity to develop targeted treatments to reverse or prevent physiological or chemotherapy-induced oocyte aging. On the immediate practical side, women with BRCA or similar mutations may need to be specially counselled for fertility preservation.

scholarly journals Oocyte maturation and quality: role of cyclic nucleotides

Reproduction ◽  
2016 ◽  
Vol 152 (5) ◽  
pp. R143-R157 ◽  
Author(s):  
R B Gilchrist ◽  
A M Luciano ◽  
D Richani ◽  
H T Zeng ◽  
X Wang ◽  
...  
Keyword(s):  
Cyclic Nucleotides ◽  
Treatment Options ◽  
Oocyte Quality ◽  
Fertility Treatment ◽  
Lower Efficiency ◽  
Oocyte Meiosis ◽  
Developmental Capacity ◽  
Oocyte Meiotic Maturation

The cyclic nucleotides, cAMP and cGMP, are the key molecules controlling mammalian oocyte meiosis. Their roles in oocyte biology have been at the forefront of oocyte research for decades, and many of the long-standing controversies in relation to the regulation of oocyte meiotic maturation are now resolved. It is now clear that the follicle prevents meiotic resumption through the actions of natriuretic peptides and cGMP – inhibiting the hydrolysis of intra-oocyte cAMP – and that the pre-ovulatory gonadotrophin surge reverses these processes. The gonadotrophin surge also leads to a transient spike in cAMP in the somatic compartment of the follicle. Research over the past two decades has conclusively demonstrated that this surge in cAMP is important for the subsequent developmental capacity of the oocyte. This is important, as oocyte in vitro maturation (IVM) systems practised clinically do not recapitulate this cAMP surge in vitro, possibly accounting for the lower efficiency of IVM compared with clinical IVF. This review particularly focuses on this latter aspect – the role of cAMP/cGMP in the regulation of oocyte quality. We conclude that clinical practice of IVM should reflect this new understanding of the role of cyclic nucleotides, thereby creating a new generation of ART and fertility treatment options.

scholarly journals Gm364 coordinates MIB2/DLL3/Notch2 to regulate female fertility through AKT activation

2021 ◽  
Author(s):  
Liang-Jian Chen ◽  
Na-Na Zhang ◽  
Chun-Xiang Zhou ◽  
Zhi-Xia Yang ◽  
Yan-Ru Li ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
Mitochondrial Membrane ◽  
Transmembrane Protein ◽  
Oocyte Quality ◽  
Female Fertility ◽  
Integral Membrane Proteins ◽  
Normal Operation ◽  
Primordial Follicles ◽  
Akt Activation ◽  
Oocyte Meiosis

AbstractMany integral membrane proteins might act as indispensable coordinators in specific functional microdomains to maintain the normal operation of known receptors, such as Notch. Gm364 is a multi-pass transmembrane protein that has been screened as a potential female fertility factor. However, there have been no reports to date about its function in female fertility. Here, we found that global knockout of Gm364 decreased the numbers of primordial follicles and growing follicles, impaired oocyte quality as indicated by increased ROS and γ-H2AX, decreased mitochondrial membrane potential, decreased oocyte maturation, and increased aneuploidy. Mechanistically, Gm364 directly binds and anchors MIB2, a ubiquitin ligase, on the membrane. Subsequently, membrane MIB2 ubiquitinates and activates DLL3. Next, the activated DLL3 binds and activates Notch2, which is subsequently cleaved within the cytoplasm to produce NICD2, the intracellular active domain of Notch2. Finally, NICD2 can directly activate AKT within the cytoplasm to regulate oocyte meiosis and quality.

scholarly journals A Nuclear and Cytoplasmic Characterization of Bovine Oocytes Reveals That Cysteamine Partially Rescues the Embryo Development in a Model of Low Ovarian Reserve

Animals ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1936
Author(s):  
Valentina Lodde ◽  
Alberto Maria Luciano ◽  
Giulia Musmeci ◽  
Ileana Miclea ◽  
Irene Tessaro ◽  
...  
Keyword(s):  
Embryo Development ◽  
Positive Impact ◽  
Antral Follicle ◽  
Oocyte Quality ◽  
Antral Follicle Count ◽  
Culture Conditions ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
Ovarian Aging

Decreased oocyte quality is a major determinant of age-associated fertility decline. Similarly, individuals affected by early ovarian aging carry low-quality oocytes. Using an established bovine model of early ovarian aging, we investigated key features of ‘quality’ oocyte maturation, associated with the onset of egg aneuploidy and reproductive aging, such as histone modifications, mitochondria distribution and activity, reduced glutathione (GSH) content, and gap junction functionality. Bovine ovaries were classified according to the antral follicle count (AFC), and the retrieved oocytes were processed immediately or matured in vitro. We observed alterations in several cellular processes, suggesting a multifactorial etiology of the reduced oocyte quality. Furthermore, we performed a rescue experiment for one of the parameters considered. By adding cysteamine to the maturation medium, we experimentally increased the free radical scavenger ability of the ‘low competence’ oocytes and obtained a higher embryo development. Our findings show that adopting culture conditions that counteract the free radicals has a positive impact on the quality of ‘compromised’ oocytes. Specifically, cysteamine treatment seems to be a promising option for treating aging-related deficiencies in embryo development.

scholarly journals CHK2 sets the stage for CK1 in oocyte quality control

2018 ◽  
Vol 25 (6) ◽  
pp. 1007-1009 ◽  
Author(s):  
Sebastian Kehrloesser ◽  
Marcel Tuppi ◽  
Volker Dötsch
Keyword(s):  
Quality Control ◽  
Oocyte Quality

scholarly journals Comparison of the toxic effects of different mycotoxins on porcine and mouse oocyte meiosis

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5111 ◽  
Author(s):  
Yujie Lu ◽  
Yue Zhang ◽  
Jia-Qian Liu ◽  
Peng Zou ◽  
Lu Jia ◽  
...  
Keyword(s):  
Oocyte Maturation ◽  
Animal Feed ◽  
Polar Body ◽  
Oocyte Quality ◽  
Mouse Oocyte ◽  
Toxic Effects ◽  
Mouse Oocytes ◽  
Oocyte Meiosis ◽  
Porcine Oocyte ◽  
Polar Body Extrusion

Background Aflatoxin B1 (AFB1), deoxynivalenol (DON), HT-2, ochratoxin A (OTA), zearalenone (ZEA) are the most common mycotoxins that are found in corn-based animal feed which have multiple toxic effects on animals and humans. Previous studies reported that these mycotoxins impaired mammalian oocyte quality. However, the effective concentrations of mycotoxins to animal oocytes were different. Methods In this study we aimed to compare the sensitivity of mouse and porcine oocytes to AFB1, DON, HT-2, OTA, and ZEA for mycotoxin research. We adopted the polar body extrusion rate of mouse and porcine oocyte as the standard for the effects of mycotoxins on oocyte maturation. Results and Discussion Our results showed that 10 μM AFB1 and 1 μM DON significantly affected porcine oocyte maturation compared with 50 μM AFB1 and 2 μM DON on mouse oocytes. However, 10 nM HT-2 significantly affected mouse oocyte maturation compared with 50 nM HT-2 on porcine oocytes. Moreover, 5 μM OTA and 10 μM ZEA significantly affected porcine oocyte maturation compared with 300 μM OTA and 50 μM ZEA on mouse oocytes. In summary, our results showed that porcine oocytes were more sensitive to AFB1, DON, OTA, and ZEA than mouse oocytes except HT-2 toxin.

scholarly journals Maternal control of early embryogenesis in mammals

2015 ◽  
Vol 27 (6) ◽  
pp. 880 ◽  
Author(s):  
Kun Zhang ◽  
George W. Smith
Keyword(s):  
Maternal Effect ◽  
Oocyte Quality ◽  
Farm Animals ◽  
Maternal Control ◽  
Close Link ◽  
Embryonic Genome Activation ◽  
Ovarian Aging ◽  
Embryonic Genome ◽  
Maternal Effect Genes ◽  
Genome Activation

Oocyte quality is a critical factor limiting the efficiency of assisted reproductive technologies (ART) and pregnancy success in farm animals and humans. ART success is diminished with increased maternal age, suggesting a close link between poor oocyte quality and ovarian aging. However, the regulation of oocyte quality remains poorly understood. Oocyte quality is functionally linked to ART success because the maternal-to-embryonic transition (MET) is dependent on stored maternal factors, which are accumulated in oocytes during oocyte development and growth. The MET consists of critical developmental processes, including maternal RNA depletion and embryonic genome activation. In recent years, key maternal proteins encoded by maternal-effect genes have been determined, primarily using genetically modified mouse models. These proteins are implicated in various aspects of early embryonic development, including maternal mRNA degradation, epigenetic reprogramming, signal transduction, protein translation and initiation of embryonic genome activation. Species differences exist in the number of cell divisions encompassing the MET and maternal-effect genes controlling this developmental window. Perturbations of maternal control, some of which are associated with ovarian aging, result in decreased oocyte quality.

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