title: The nuclear mitotic apparatus (NuMA) protein: localization and dynamics in human oocytes, fertilization and early embryos.
abstract: The oocyte's meiotic spindle is a dynamic structure that relies on microtubule organization and regulation by centrosomes. Disorganization of centrosomal proteins, including the nuclear mitotic apparatus (NuMA) protein and the molecular motor complex dynein/dynactin, can lead to chromosomal instability and developmental abnormalities. The present study reports the distribution and function of these proteins in human oocytes, zygotes and early embryos. A total of 239 oocytes, 90 zygotes and discarded embryos were fixed and analyzed with confocal microscopy for NuMA and dynactin distribution together with microtubules and chromatin. Microtubule-associated dynein-dependent transport functions were explored by inhibiting phosphatase and ATPase activity with sodium-orthovanadate (SOV). At germinal vesicle (GV) stages, NuMA was dispersed across the nucleoplasm. After GV breaks down, NuMA became cytoplasmic before localizing at the spindle poles in metaphase I and II oocytes. Aberrant NuMA localization patterns were found during oocyte in vitro maturation. After fertilization, normal and abnormal pronuclear stage zygotes and embryos displayed translocation of NuMA to interphase nuclei. SOV treatment for up to 2 h induced lower maturation rates with chromosomal scattering and ectopic localization of NuMA. Accurate distribution of NuMA is important for oocyte maturation, zygote and embryo development in humans. Proper assembly of NuMA is likely necessary for bipolar spindle organization and human oocyte developmental competence.
authors.affiliation: Centro de Estudios en Ginecología y Reproducción (CEGyR), Buenos Aires, Argentina.
authors.forename: Cristian
authors.initials: C
authors.lastname: Alvarez Sedó
authors.forename: Heide
authors.initials: H
authors.lastname: Schatten
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Combelles
authors.forename: Vanesa Y
authors.initials: VY
authors.lastname: Rawe
mesh_terms: D037881:Aborted Fetus; D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000328:Adult; D034961:Antigens, Nuclear / Q000502:physiology; D018797:Cell Cycle Proteins; D002467:Cell Nucleus / Q000378:metabolism / Q000648:ultrastructure; D018385:Centrosome / Q000378:metabolism / Q000648:ultrastructure; D002875:Chromosomes; D000072159:Dynactin Complex; D004398:Dyneins / Q000502:physiology; D004622:Embryo, Mammalian / Q000196:embryology / Q000378:metabolism* / Q000648:ultrastructure; D047108:Embryonic Development; D005260:Female; D005306:Fertilization; D006801:Humans; D008677:Metaphase; D018613:Microscopy, Confocal; D008869:Microtubule-Associated Proteins / Q000502:physiology; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D034521:Nuclear Matrix-Associated Proteins / Q000502:physiology; D009865:Oocytes / Q000254:growth & development / Q000378:metabolism* / Q000648:ultrastructure; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011247:Pregnancy; D008941:Spindle Apparatus / Q000378:metabolism* / Q000648:ultrastructure; D014404:Tubulin / Q000502:physiology; D014638:Vanadates / Q000494:pharmacology; D015053:Zygote
chemical_list: D034961:Antigens, Nuclear; D018797:Cell Cycle Proteins; D000072159:Dynactin Complex; D008869:Microtubule-Associated Proteins; C050045:NUMA1 protein, human; D034521:Nuclear Matrix-Associated Proteins; D014404:Tubulin; D014638:Vanadates; D010744:Phosphoric Monoester Hydrolases; D000251:Adenosine Triphosphatases; D004398:Dyneins