logotype

 

Greg Fitzharris, Phd

Associate professor
Université de Montréal
Department of obstetrics and gynaecology
CR-CHUM, Tour Viger
900 St-Denis, Montréal
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Telephone : 514-890 8000
Website : www.fitzharrislab.com

Field of Research

  • Oocyte and embryo development

Recent Results

Causes and consequences of oocyte and embryo aneuploidy

Our laboratory is interested in why oocytes from older mothers are more likely to have the wrong number of chromosomes (termed ‘aneuploidy’) than oocytes from younger mothers. These ‘aneuploid’ eggs are developmentally-compromised, and oocyte aneuploidy is thus a leading cause of age-related infertility. Over the past several years we have have been investigating the reasons why aneuploidy occurs in oocytes, focussing on the spindle – the part of the cell responsible for segregating chromosomes at the time of cell division. Most recently we have shown that anaphase, the process by which the spindle executes chromosome segregation, occurs via kinetochore microtubules in the mammalian oocyte (Current Biology, 2012). This is significant since it had been predicted from lower organisms that kinetochore microtubules may not be necessary in oocytes. Subsequently, we have just completed out first study using naturally-aged mice, which experience age related aneuploidy similar to humans. Excitingly, we have found that establishment of kinetochore microtubules is defective in oocytes from aged mice (Shomper et al., 2014, Cell Cycle). This provides a coherent cellular explanation as to why oocytes from older mice are prone to chromosome missegregation and aneuploidy. The reasons for this defective spindle function in oocytes from older mice are unclear, and are now a major focus of the lab.  

Similar to oocytes, chromsome segregation is also highly error prone in the mammalian preimplantation embryo. We have therefore also been applying our imaging approaches to begin to examine spindle dynamics during early embryogenesis, and have already found striking differences in the way MTs are organised in embryos compared to somatic cells. Most notably we have found that microtubules self-organise in interphase embryos despite the presence of centrosomes (Howe and FitzHarris, 2013. Cell Cycle). In addition we found a shift in the way spindle length is regulated during embryogenesis (Yamagata and FitzHarris., 2013. Cell Cycle). We believe that understanding the reasons for chromosome segregation errors in oocytes and embryos cannot rely on extrapolation from ‘traditional’ model systems, but that these processes are studied directly in this unique cellular environment.

Lab members

 

Name

Position

email

Shoma Nakagawa

RA

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Jenna Haverfield

Postdoc

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Cayetana Vazquez

MSc

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Original research articles

Shomper, Lappa, and FitzHarris G.Establishment of kinetochore microtubules is defective in oocytes from naturally aged mice.Cell Cycle. 2014.

Howe K and FitzHarris G. A non-canonical mode of microtubule organisation operates throughout preimplantation development in mouse. Cell Cycle. 2013. 12(10):1616-24

Zhou C, Fitzharris G, Alper SL, Baltz JM. Na+ /H+ exchange is inactivated during mouse oocyte meiosis, facilitating glycine accumulation that maintains cell volume in embryos. J Cell Physiol. 2013 Apr 1.

Yamagata K, FitzHarris G. 4D imaging reveals a shift in chromosome segregation dynamics during mouse pre-implantation development. Cell Cycle. 2013. Jan 1;12

FitzHarris, G Anaphase-B precedes Anaphase-A in the mouse egg. Current Biology, 2012. 22: 437-444.

Illingworth C, Pirmadjid N, Serhal P, Howe K, Fitzharris G. MCAK regulates chromosome alignment but is not necessary for preventing aneuploidy in mouse oocyte meiosis I. Development. 2010 Jul;137(13):2133-8.

Fitzharris G. A shift from kinesin 5-dependent metaphase spindle function during preimplantation development in mouse. Development. 2009 Jun;136(12):2111-9.

Wang L, Wang ZB, Zhang X, FitzHarris G, Baltz JM, Sun QY, Liu XJ. Brefeldin A disrupts asymmetric spindle positioning in mouse oocytes. Dev Biol. 2008 Jan1;313(1):155-66.

FitzHarris G, Siyanov V, Baltz JM. Granulosa cells regulate oocyte intracellular pH against acidosis in preantral follicles by multiple mechanisms. Development. 2007 Dec;134(23):4283-95.

FitzHarris G, Marangos P, Carroll J. Changes in endoplasmic reticulum structure during mouse oocyte maturation are controlled by the cytoskeleton and cytoplasmic dynein. Dev Biol. 2007 May 1;305(1):133-44.

Fitzharris G, Baltz JM. Granulosa cells regulate intracellular pH of the murine growing oocyte via gap junctions: development of independent homeostasis during oocyte growth. Development. 2006 Feb;133(4):591-9.

FitzHarris G, Larman M, Richards C, Carroll J. An increase in [Ca2+]i is sufficient but not necessary for driving mitosis in early mouse embryos. J Cell Sci. 2005 Oct 1;118(Pt 19):4563-75.

Erdogan S, FitzHarris G, Tartia AP, Baltz JM. Mechanisms regulating intracellular pH are activated during growth of the mouse oocyte coincident with acquisition of meiotic competence. Dev Biol. 2005 Oct 1;286(1):352-60.

Dumollard R, Marangos P, Fitzharris G, Swann K, Duchen M, Carroll J. Sperm-triggered [Ca2+] oscillations and Ca2+ homeostasis in the mouse egg have an absolute requirement for mitochondrial ATP production. Development. 2004 Jul;131(13):3057-67.

Marangos P, FitzHarris G, Carroll J. Ca2+ oscillations at fertilization in mammals are regulated by the formation of pronuclei. Development. 2003 Apr;130(7):1461-72.  

FitzHarris G, Marangos P, Carroll J. Cell cycle-dependent regulation of structure of endoplasmic reticulum and inositol 1,4,5-trisphosphate induced Ca2+ release in mouse oocytes and embryos. Mol Biol Cell. 2003 Jan;14(1):288-301.

Review articles  

Howe K and FitzHarris G. Recent insights into spindle function in mammalian oocytes and embryos. Biology of Reproduction 2013.

FitzHarris G, Baltz JM. Regulation of intracellular pH during oocyte growth and maturation in mammals. Reproduction. 2009 Oct;138(4):619-27.

Halet G, Marangos P, Fitzharris G, Carroll J. Ca2+ oscillations at fertilization in mammals. Biochem Soc Trans. 2003 Oct;31(Pt 5):907-11.

Carroll J, FitzHarris G, Marangos P, Halet G. Ca2+ signalling and cortical re-organisation during the transition from meiosis to mitosis in mammalian oocytes. Eur J Obstet Gynecol Reprod Biol. 2004 Jul 1;115 Suppl 1:S61-7.