The root of reduced fertility in aged women and possible therapentic options: Current status and future perspects

Qiao, Jie; Wang, Zhenbo; Feng, Haoran; Miao, Yi‐Liang; Wang, Qiang; Yu, Yang; Wei, Yanchang; Yan, Jie; Wang, Weihua; Shen, Wei; Sun, Shao‐Chen; Schatten, Heide; Sun, Qing‐Yuan

doi:10.1016/j.mam.2013.06.001

Cited by 130 publications

(107 citation statements)

References 362 publications

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“…It is estimated that 20% of human oocytes are aneuploid, and mistakes in meiotic chromosome segregation account for one third of all pregnancy losses (Hassold and Hunt, 2001;Qiao et al, 2014;Wang et al, 2011). Both MI and MII exits are key events in maintaining the euploidy of oocytes.…”

Section: Discussionmentioning

confidence: 99%

Loss of protein phosphatase 6 in oocytes causes failure of meiosis II exit and impaired female fertility

Wang

Teng³

et al. 2015

Journal of Cell Science

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Dynamic protein phosphorylation and dephosphorylation, mediated by a conserved cohort of protein kinases and phosphatases, regulate cell cycle progression. Among the well-known PP2A-like protein phosphatases, protein phosphatase 6 (PP6) has been analyzed in mammalian mitosis, and Aurora A has recently been identified as its key substrate. However, the functions of PP6 in meiosis are still entirely unknown. To identify the physiological role of PP6 in female gametogenesis, Ppp6c F/F mice were first generated and crossed with Zp3-Cre mice to selectively disrupt Ppp6c expression in oocytes. Here, we report for the first time that PP6c is dispensable for oocyte meiotic maturation but essential for exit from meiosis II (MII) after fertilization. Depletion of PP6c caused an abnormal MII spindle and disrupted MII cytokinesis, resulting in zygotes with high risk of aneuploidy and defective early embryonic development, and thus severe subfertility. We also reveal that PP6 inactivation interferes with MII spindle formation and MII exit owing to increased Aurora A activity, and that Aurora A inhibition with MLN8237 can rescue the PP6c depletion phenotype. In conclusion, our findings uncover a hitherto unknown role for PP6 as an indispensable regulator of oocyte meiosis and female fertility.

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Section: Discussionmentioning

confidence: 99%

Loss of protein phosphatase 6 in oocytes causes failure of meiosis II exit and impaired female fertility

Wang

Teng³

et al. 2015

Journal of Cell Science

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“…The variation in quantity of mitochondria, even if recorded in some studies, is controversial [9,52], and likely not indicative of a specific damage, being more relevant the metabolic changes. The bioenergetic deficit is one of the most accountable and intriguing factors thought responsible for age-related reproductive failure [6].…”

Section: Ooplasmic Aggregatesmentioning

confidence: 99%

“…At present, ART cannot fully compensate this natural decline of fertility [4,2]. Thirty-five years is considered as a watershed in terms of fertility; indeed, women in the late of third decade or early of fourth decade may be reasonably considered in an advanced reproductive stage, but also in a borderline aging [5,6].…”

Section: Introductionmentioning

confidence: 99%

“…Oocyte quality profoundly affects fertilization, survival of early embryo, maintenance of pregnancy, and fetal development as well [6]. The specific morphological features of oocytes observed by phase contrast microscopy (PCM) are important and irreplaceable predictive markers of ART success, but a low-resolution morphological assessment may be not sufficient to fully evaluate oocyte developmental competence and age-related damages [16,17].…”

Section: Introductionmentioning

confidence: 99%

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Ultrastructural markers of quality are impaired in human metaphase II aged oocytes: a comparison between reproductive and in vitro aging

Bianchi

Macchiarelli

Micara

et al. 2015

J Assist Reprod Genet

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“…Errors in chromosome separation leads to the production of aneuploid eggs, which is believed to be the main cause of infertility, abortion and many genetic diseases in humans. 1 Oocyte meiotic maturation is characterized by asymmetric division, producing a small polar body and a large mature egg containing most of the ooplasm. Chromosome segregation is driven by the spindle microtubules.…”

Section: Introductionmentioning

confidence: 99%

Centriolin, a centriole-appendage protein, regulates peripheral spindle migration and asymmetric division in mouse meiotic oocytes

et al. 2017

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Unlike somatic cells mitosis, germ cell meiosis consists of 2 consecutive rounds of division that segregate homologous chromosomes and sister chromatids, respectively. The meiotic oocyte is characterized by an absence of centrioles and asymmetric division. Centriolin is a relatively novel centriolar protein that functions in mitotic cell cycle progression and cytokinesis. Here, we explored the function of centriolin in meiosis and showed that it is localized to meiotic spindles and concentrated at the spindle poles and midbody during oocyte meiotic maturation. Unexpectedly, knockdown of centriolin in oocytes with either siRNA or Morpholino micro-injection, did not affect meiotic spindle organization, cell cycle progression, or cytokinesis (as indicated by polar body emission), but led to a failure of peripheral meiotic spindle migration, large polar body emission, and 2-cell like oocytes. These data suggest that, unlike in mitotic cells, the centriolar protein centriolin does not regulate cytokinesis, but plays an important role in regulating asymmetric division of meiotic oocytes.

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The root of reduced fertility in aged women and possible therapentic options: Current status and future perspects

Cited by 130 publications

References 362 publications

Loss of protein phosphatase 6 in oocytes causes failure of meiosis II exit and impaired female fertility

Loss of protein phosphatase 6 in oocytes causes failure of meiosis II exit and impaired female fertility

Ultrastructural markers of quality are impaired in human metaphase II aged oocytes: a comparison between reproductive and in vitro aging

Centriolin, a centriole-appendage protein, regulates peripheral spindle migration and asymmetric division in mouse meiotic oocytes

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