• This unusual maturation unravels atypical spindle formation but is rescued by inhibiting integrin ß1 or Grb7 binding to the EGFR. (bvsalud.org)
  • These oocytes are protected from abnormal meiotic spindle formation through the recruitment of O-GlcNAcylated Grb7, and OGT (O-GlcNAc transferase), the enzyme responsible for O-GlcNAcylation processes, in the integrin ß1-EGFR complex. (bvsalud.org)
  • Furthermore, an O-GlcNAcylation increase (by inhibition of O-GlcNAcase), the glycosidase that removes O-GlcNAc moieties, or decrease (by inhibition of OGT) amplifies oocyte spindle defects when follicular cells are absent highlighting a control of the meiotic spindle by the OGT-O-GlcNAcase duo. (bvsalud.org)
  • Works in various organisms have revealed that the kinase is involved in centrosome separation, duplication and maturation as well as in bipolar spindle assembly and stability. (lookformedical.com)
  • Once the kinetochores of chromosomes are correctly attached to bipolar spindles and the SAC is satisfied, the MAD2L1BP, best known as p31comet, binds mitosis arrest deficient 2 (MAD2) and recruits the AAA+-ATPase TRIP13 to disassemble the mitotic checkpoint complex (MCC), leading to the cell-cycle progression. (bvsalud.org)
  • Human oocyte maturation arrest represents one of the severe conditions for female patients with primary infertility. (bvsalud.org)
  • Together, our studies identified and characterized novel biallelic variants in MAD2L1BP responsible for human oocyte maturation arrest at MI, and thus prompted new therapeutic avenues for curing female primary infertility. (bvsalud.org)
  • The oocyte (eggs, ova, ovum) is arrested at an early stage of the first {{meiosis))(first meiotic) division as a primary oocyte (primordial follicle) within the ovary . (edu.au)
  • The breakdown of the germinal vesicle indicates a resumption of meiosis and the extrusion of the first polar body (1 PB) indicates completion of the first meiotic division in human oocytes. (edu.au)
  • In the reproductive system, despite Gsα being associated with oocyte meiotic arrest in vitro, the exact role of Gsα in female fertility in vivo remains largely unknown. (edu.au)
  • meiosis in Gsα-deficient oocytes precociously resumed in only 43% of antral follicles from mutant mice, indicating that alteration of meiotic pause was not the key factor in infertility. (edu.au)
  • Although poor oocyte quality accounts for most female fertility problems, little is known about how oocytes maintain cellular fitness, or why their quality eventually declines with age2. (bvsalud.org)
  • In this study, by whole-exome sequencing (WES), we identified homozygous and compound heterozygous MAD2L1BP variants in three families with female patients diagnosed with primary infertility owing to oocyte metaphase I (MI) arrest. (bvsalud.org)
  • Here we show that conditional knockout (cKO) of Mtor in either primordial or growing oocytes caused infertility but differentially affected oocyte quality, granulosa cell fate, and follicular development. (edu.au)
  • Once the kinetochores of chromosomes are correctly attached to bipolar spindles and the SAC is satisfied, the MAD2L1BP, best known as p31comet, binds mitosis arrest deficient 2 (MAD2) and recruits the AAA+-ATPase TRIP13 to disassemble the mitotic checkpoint complex (MCC), leading to the cell-cycle progression. (bvsalud.org)
  • Yet, how healthy oocytes balance essential mitochondrial activity with the production of ROS is unknown. (bvsalud.org)
  • Here we show that oocytes evade ROS by remodelling the mitochondrial electron transport chain through elimination of complex I. Combining live-cell imaging and proteomics in human and Xenopus oocytes, we find that early oocytes exhibit greatly reduced levels of complex I. This is accompanied by a highly active mitochondrial unfolded protein response, which is indicative of an imbalanced electron transport chain. (bvsalud.org)
  • Furthermore, the level of ROS (reactive oxygen species) and the mitochondrial aggregation increased, and antioxidant glutathione (GSH) content, ATP level, mtDNA copy number, and mitochondrial membrane potential decreased in Gsα-deficient oocytes. (edu.au)
  • RESULTS: Oocytes from reproductively old mice were smaller than young counterparts in terms of GV area (446.42 ± 4.15 vs. 416.79 ± 5.24 µm2, p (bvsalud.org)
  • There were no differences in the morphokinetic parameters of oocyte maturation between oocytes from reproductively young and old mice with respect to time to germinal vesicle breakdown (GVBD) (1.03 ± 0.03 vs. 1.01 ± 0.04 h), polar body extrusion (PBE) (8.56 ± 0.11 vs. 8.52 ± 0.15 h), duration of meiosis I (7.58 ± 0.10 vs. 7.48 ± 0.11 h), and kinetics of cumulus expansion (0.093 ± 0.002 vs. 0.089 ± 0.003 µm/min). (bvsalud.org)
  • Oocyte-specific deletion of Gsα induces oxidative stress and deteriorates oocyte quality in mice [1] "The stimulatory heterotrimeric Gs protein alpha subunit (Gsα) is a ubiquitous guanine nucleotide-binding protein that regulates the intracellular cAMP signaling pathway and consequently participates in a wide range of biological events. (edu.au)
  • Here, we generated oocyte-specific Gsα knockout mice by using the Cre/LoxP system. (edu.au)
  • GV oocytes from mutant mice showed early-stage apoptosis. (edu.au)
  • Oocyte stage-specific effects of MTOR determine granulosa cell fate and oocyte quality in mice [2] "MTOR (mechanistic target of rapamycin) is a widely recognized integrator of signals and pathways key for cellular metabolism, proliferation, and differentiation. (edu.au)
  • Early oocytes are also classified as immature (germinal vesicle (GV) or metaphase I (MI) stage). (edu.au)
  • Therefore, MTOR-dependent pathways in primordial or growing oocytes differentially affected downstream processes including follicular development, sex-specific identity of early granulosa cells, maintenance of oocyte genome integrity, oocyte gene expression, meiosis, and preimplantation developmental competence. (edu.au)
  • Meanwhile, the Gsα knockout-induced decline in oocyte quality and low developmental potential was partially rescued by antioxidant supplementation. (edu.au)
  • However, to recapitulate mammalian oogenesis and produce fertilizable oocytes in vitro is a complex process involving several different cell types, precise follicular cell-oocyte reciprocal interactions, a variety of nutrients and combinations of cytokines, and precise growth factors and hormones depending on the developmental stage. (edu.au)
  • Complete in vitro oogenesis: retrospects and prospects [3] "In reality the vast majority of oocytes formed from primordial germ cells (PGCs) will undergo apoptosis, or other forms of cell death. (edu.au)
  • reported in vitro procedures that appear to reproduce efficiently these conditions allowing for the production, completely in a dish, of a relatively large number of oocytes that are fertilizable and capable of giving rise to viable offspring in the mouse. (edu.au)