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Teruko Taketo, Ph.D.

Professor

McGill University

Department of Surgery

Research Institute of McGill University

Hospital Center, Room EM03200

1001 Decarie Blvd

Montreal, Quebec, H4A 3J1

This email address is being protected from spambots. You need JavaScript enabled to view it.

(514) 934-1934 x34197

(514) 843-1457

Field of research:

Women’s fertility depends on the number and quality of oocytes in reserve, both of which are established by birth and decline with age. The oocyte reserve is limited because all oogonia stop proliferation and enter meiosis in fetal life, and, in addition, more than half of the initial oocyte population is eliminated before birth. During this period, homologous chromosomes pair, synapse and recombine; these events are essential for securing proper chromosome segregation in oocytes and generating genetic diversity in the offspring. Our main hypothesis is that a failure in meiotic synapsis leads to apoptotic elimination of oocytes carrying asynapsis, thus minimizing the risk of aneuploidy in embryos. Specifically, we will (1) clarify the regulatory mechanism of the caspase 9-mediated apoptotic pathway responsible for oocyte elimination, (2) determine the mechanism by which persistent chromosome asynapsis leads to oocyte demise, and (3) assess the integrity of oocytes which have survived when apoptotic elimination is circumvented. We are also interested in the regulation of spindle assembly and chromosome segregation during the second meiotic division in mature oocytes 

 

Summary of recent results:

We have established a new method for analyzing the number and chromosomal structures in individual oocytes dissociated from fetal and neonatal mouse ovaries (Taketo, 2012), and shown that the majority of oocytes are eliminated by caspase 9-dependent mitochondrial apoptotic pathway during normal ovarian development (Ene et al., 2013). However, we also found that caspasae 9 is constitutively activated in most oocytes, leading to our current hypothesis that the life or death of oocytes is determined by the control of caspase 9 activity by endogenous apoptosis inhibitors (IAPs) as well as mitochondrial IAP inhibitors such as ARTS and SMAC/DIABLO. We are currently testing this hypothesis using various mutant mice as well as small molecule inhibitors in ovarian culture. We are also examining the link between chromosome asynapsis and apoptotic death in the oocytes carrying XO, XY, or Robertsonian translocation chromosomes (Taketo & Naumova, 2013). We have previously demonstrated that the oocytes of XY sex-reversed females reach the second metaphase but the second meiotic spindle is not adequately assembled and sister chromatids fail to segregate upon fertilization or activation. By replacing the ooplasm prior to maturation, the nucleus of an XY oocyte goes through the second meiotic division and yields healthy offspring (Obata et al., 2008). Our third project is to identify the cytoplasmic components responsible for the impairment of the meiotic spindle assembly in the XY oocyte, and to delineate the controlling mechanisms of the meiotic spindle assembly in normal XX oocytes (Xu et al., 2012; 2014; Vernet et al. 2014).

 

List of laboratory members:

Name

Position

Adel Morwad

Postdoctoral fellow

Jia-Qiao Zhu

Visiting scholar

Debra Fullon

Postdoctoral fellow

 Yuri Chung

Graduate student 

 

List of publications (selected):

Amleh A, Ledee N, Saeed J, Taketo T (1996) Competence of XY oocytes from the B6.YDOM sex-reversed female mouse for maturation, fertilization, and embryonic development in vitro. Developmental Biology 178: 263-275.

Vanderhyden BC, Macdonald EA, Merchant-Larios H, Fernandez A, Amleh A, Nasseri R, Taketo T (1997) Interactions between the oocyte and cumulus cells in the ovary of the B6.YTIR sex-reversed female mouse. Biology of Reproduction 57: 641-646.

Amleh A, Taketo T (1998) Live-borns from XX but not XY oocytes in the chimeric ovary composed of B6.YTIR and XX cells. Biology of Reproduction 58: 574-582.

Amleh A, Smith L, Chen H-Y, Taketo T (2000) Both nuclear and cytoplasmic components are defective in oocytes of the B6.YTIR sex-reversed female mouse. Developmental Biology 219: 277-286.

McClellan KA, Gosden R, Taketo T (2003) Continuous loss of oocytes throughout meiotic prophase in the normal mouse ovary. Developmental Biology 258: 334-348.

Park E-H, Taketo T (2003) Onset and progress of meiotic prophase in the oocytes in the B6.YTIR sex-reversed mouse ovary. Biology of Reproduction 69: 1879-1889.

Taketo T, Lee C-H, Zhang J, Li Y-M, Lee C-YG, Lau Y-FC (2005) Expression of SRY proteins in both normal and sex-reversed XY fetal mouse gonads. Developmental Dynamics 233: 612-622.

Villemure M, Chen H-Y, Kurokawa M, Fissore RM, Taketo T (2007) The presence of X-and Y-chromosomes in oocytes leads to impairment in the progression of the second meiotic division. Developmental Biology 301: 1-13.

Alton M, Taketo T (2007) Switch from BAX-dependent to BAX-independent germ cell loss during the development of fetal mouse ovaries. J. Cell Science 120: 417-424.

Alton M, Lau MP, Villemure M, Taketo T (2008) The behavior of the X- and Y-chromosomes in the oocyte during meiotic prophase in the B6.YTIR sex-reversed mouse ovary. Reproduction 135: 241-252.

Obata Y, Villemure M, Kono T, Taketo T (2008) Transmission of Y-chromosomes from XY female mice was made possible by replacement of cytoplasm during oocyte maturation. PNAS USA 105: 13918-13923.

Park S, Zeidan KT, Shin JS, T Taketo (2011) SRY upregulation of SOX9 is inefficient and delayed, allowing ovarian differentiation, in the B6.YTIR gonad. Differentiation 82: 18-27.

Xu B-Z, Obata Y, Cao F, Taketo T (2012) The presence of the Y-chromosome, not the absence of the second X-chromosome, alters the mRNAs stored in the fully grown XY mouse oocyte. PLos One 7: e4048.

Taketo T (2012) Microspread oocyte preparations for the analysis of meiotic prophase progression with improved recovery by cytospin centrifugation. Methods in Molecular Biology 825: 173-181.

Ene AC, Park S, Edelmann W, Taketo T (2013) Caspase 9 is constitutively activated in mouse oocytes and plays a key role in oocyte elimination during meiotic prophase progression. Developmental Biology 377: 213-223.

Moawad A, Tan SL, Xu B, Chen H-Y, Taketo T (2013) L-carnitine supplementation during vitrification of mouse oocytes at the germinal vesicle stage improves preimplantation development following maturation and fertilization in vitro.

Biology of Reproduction 88: 104, 1-8.

Taketo T, Naumova AK (2013) Oocyte heterogeneity with respect to the meiotic silencing of unsynapsed X chromosomes in the XY female mouse. Chromosoma 122: 337-349.

Naumova AK, Leung J, Fayer S, Boateng K, Camerini-Otero RD, Taketo T (2013) Response to asynapsis differs between autosomal translocations and sex chromosomes in spermatocytes from Robertsonian translocation carriers. Plos One 9: e75970.

Xu B, Noohi S, Shin JS, Tan SL, Taketo T (2014) Bi-directional communication with cumulus cells involved in the deficiency of XY oocytes in the components essential for proper second meiotic spindle assembly. Developmental Biology 385: 242-252.

Vernet N, Szot M, Mahadevaiah SK, Ellis PJI, Decarpentrie F, Ojarikre OA, Rattigan A, Taketo T, Burgoyne PS (2014) The expression of Y-encoded Zfy2 in XY mouse oocytes triggers subsequent preimplantation embryonic failure and infertility. Development 141: 855-866.

Moawad AR, Xu B, Tan SL, Taketo T (2014) L-carnitine supplementation during vitrification of mouse germinal vesicle stage–oocytes and their subsequent in vitro maturation improves meiotic spindle configuration and mitochondrial distribution in metaphase II oocytes. Human Reproduction 29: 2256-2268.