THE OVERVIEW
A leading cause of infertility is a defect in the woman’s egg (oocyte) that causes it to have the wrong number of chromosomes. These so-called ‘aneuploid’ oocytes cause developmental conditions such as Down’s, and can lead to pregnancy loss. These errors become increasingly common with advancing maternal age, and are therefore a major reason why older women experience difficulties establishing a healthy pregnancy.
The part of the cell responsible for maintaining the correct chromosome number is the spindle - a complex biological machine that gathers and sorts chromosomes at the time of cell division, and dispatches them to the two daughter cells in a process termed chromosome segregation. Why chromosome segregation often goes wrong in oocytes is poorly understood. Once the oocyte is fertilised the first several cell divisions in the newly forming embryo are also highly prone to chromosome miss-segregation. These embryonic errors are also associated with decreased fertility, but their causes and consequences remain obscure.
Research in our laboratory is aimed at understanding how healthy eggs and embryos are made, and we are particularly focussing on how and why defects in chromosome segregation can cause infertility. We specialise in the use of cutting edge microscopy techniques to analyse egg and embryo function ex-vivo. We have important collaborators in Montreal and elsewhere, including close collaborations with Hugh Clarke of the CRRD, and the MUHC assisted reproduction facility.
Ongoing projects in the lab include:
● Analysis of spindle microtubule dynamics in oocytes.
● Evaluation of the changes in spindle function that occur with maternal age, and how this causes chromosome segregation error.
● Analysis of the mechanism of chromosome segregation in embryos, and the causes of segregation errors.
● Analysis of the mechanism of cytokinesis in oocytes and embryos.
●Analysis of kinetochore structure and function during early development.
The lab is currently financed by funding from CIHR, NSERC, and Fondation J-L Lévesque.
THE IMAGES
THE IMAGES
THE PUBLICATIONS
Oocyte and embryo culture under oil profoundly alters effective concentrations of small molecule inhibitors. Rémillard-Labrosse G, Cohen S, Boucher É, Gagnon K, Vasilev F, Mihajlović AI, FitzHarris G. Front Cell Dev Biol. 2024 Mar 8;12:1337937. doi: 10.3389/fcell.2024.1337937.
Spindle assembly checkpoint insensitivity allows meiosis-II despite chromosomal defects in aged eggs. Mihajlović AI, Byers C, Reinholdt L, FitzHarris G. EMBO Rep. 2023 Nov 6;24(11):e57227.
Kinetochore deterioration concommitant with centromere weakening during aging in mouse oocyte meiosis-I. Yin L, Mihajlović AI, Yang G, FitzHarris G. FASEB J. 2023 May;37(5):e22922.
Imaging the subcellular viscoelastic properties of mouse oocytes. Flé G, Van Houten E, Rémillard-Labrosse G, FitzHarris G, Cloutier G. Proc Natl Acad Sci U S A. 2023 May 23;120(21):e2213836120.
Investigation of potential gender bias in the peer review system at Reproduction. Biolková, M., Moore, T., Schindler, K., Swann, K., Vail, A., Flook, L., Dick, H., Fitzharris, G., Price, C.A. and Spears, N. (2023), Learned Publishing, 36: 25-30.
Absence of a robust mitotic timer mechanism in early preimplantation mouse embryos leads to chromosome instability. Allais A, FitzHarris G Development. 2022 Jul 1;149(13):dev200391
Cell size and polarization determine cytokinesis furrow ingression dynamics in mouse embryos. Paim LMG, FitzHarris G. Proc Natl Acad Sci U S A. 2022 Mar 22;119(12).
Distinct classes of lagging chromosome underpin age-related oocyte aneuploidy in mouse. Mihajlović AI, Haverfield J, FitzHarris G. Dev Cell. 2021 Aug 23;56(16):2273-2283.e3. doi: 10.1016/j.devcel.2021.07.022. PMID: 34428397.
The impact of embryo binucleation depends upon its origin. Gomes Paim LM, FitzHarris G. Reproduction. 2020 Jul;160(1):V1-V4. doi: 10.1530/REP-20-0188.
Chromosome dynamics and spindle microtubule establishment in mouse embryos. Macaulay AD, Allais A, FitzHarris G. FASEB J. 2020 Apr 23. doi: 10.1096/fj.201902947R. Online ahead of print.
Human oocytes harboring damaged DNA can complete meiosis I. Rémillard-Labrosse G, Dean NL, Allais A, Mihajlović AI, Jin SG, Son WY, Chung JT, Pansera M, Henderson S, Mahfoudh A, Steiner N, Agapitou K, Marangos P, Buckett W, Ligeti-Ruiter J, FitzHarris G. Fertil Steril. 2020 May;113(5):1080-1089.e2. doi: 10.1016/j.fertnstert.2019.12.029. Epub 2020 Apr 8.
Sixty years of reproduction. FitzHarris G, Price C. Reproduction. 2020 Jan;159(1):E1. doi: 10.1530/REP-19-0545.
Tetraploidy causes chromosomal instability in acentriolar mouse embryos. Paim LMG, FitzHarris G. Nat Commun. 2019 Oct 23;10(1):4834. doi: 10.1038/s41467-019-12772-8.
Cell-Size-Independent Spindle Checkpoint Failure Underlies Chromosome Segregation Error in Mouse Embryos. Vázquez-Diez C, Paim LMG, FitzHarris G. Curr Biol. 2019 Jan 17. pii: S0960-9822(18)31676-2.
Segregating Chromosomes in the Mammalian Oocyte. Mihajlović AI, FitzHarris G.Curr Biol. 2018 Aug 20;28(16):R895-R907.
Monitoring Microtubule Dynamics in the Mouse Egg Using Photoactivatable-GFP-Tubulin. FitzHarris G. Methods Mol Biol. 2018;1818:137-144.
Meiosis: SUMO Keeps a Tight Grip on Sister Chromatids. Mihajlović AI, FitzHarris G. Curr Biol. 2018 Jun 4;28(11):R671-R674.
Electrical-assisted microinjection for analysis of fertilization and cell division in mammalian oocytes and early embryos. FitzHarris G, Carroll J, Swann K. Methods Cell Biol. 2018;144:431-440.
Correlative Live Imaging and Immunofluorescence for Analysis of Chromosome Segregation in Mouse Preimplantation Embryos. Vázquez-Diez C, FitzHarris G. Methods Mol Biol. 2018;1769:319-335.
Ultrafast imaging of cell elasticity with optical microelastography. Grasland-Mongrain P, Zorgani A, Nakagawa S, Bernard S, Paim LG, Fitzharris G, Catheline S, Cloutier G. Proc Natl Acad Sci U S A. 2018 Jan 30;115(5):861-866.
Causes and consequences of chromosome segregation error in preimplantation embryos. Vázquez-Diez C, FitzHarris G.Reproduction. 2018 Jan;155(1):R63-R76.
Where there was one, now there are two.Price C, FitzHarris G.Reproduction. 2018 Jan;155(1):E1.
Intrinsically Defective Microtubule Dynamics Contribute to Age-Related Chromosome Segregation Errors in Mouse Oocyte Meiosis-I. Nakagawa S, FitzHarris G. Curr Biol. 2017 Apr 3;27(7):1040-1047.
Tri-directional anaphases as a novel chromosome segregation defect in human oocytes. Haverfield J, Dean NL, Nöel D, Rémillard-Labrosse G, Paradis V, Kadoch IJ, FitzHarris G. Hum Reprod. 2017 Jun 1;32(6):1293-1303.
Quantitative Microinjection of Morpholino Antisense Oligonucleotides into Mouse Oocytes to Examine Gene Function in Meiosis-I. Nakagawa S, FitzHarris G. Methods Mol Biol. 2016;1457:217-30.
Nucleus downscaling in mouse embryos is regulated by cooperative developmental and geometric programs. Tsichlaki E, FitzHarris G. Sci Rep. 2016 Jun 20;6:28040.
Ca(2+) dynamics in oocytes from naturally-aged mice. Haverfield J, Nakagawa S, Love D, Tsichlaki E, Nomikos M, Lai FA, Swann K, FitzHarris G. Sci Rep. 2016 Jan 20;6:19357.
Micronucleus formation causes perpetual unilateral chromosome inheritance in mouse embryos. Vázquez-Diez C, Yamagata K, Trivedi S, Haverfield J, FitzHarris G. Proc Natl Acad Sci U S A. 2016 Jan 19;113(3):626-31.
Kinetochore microtubule establishment is defective in oocytes from aged mice. Shomper M, Lappa C, FitzHarris G. Cell Cycle. 2014;13(7):1171-9.
Recent insights into spindle function in mammalian oocytes and early embryos. Howe K, FitzHarris G. Biol Reprod. 2013 Sep 27;89(3):71.
A non-canonical mode of microtubule organization operates throughout pre-implantation development in mouse. Howe K, FitzHarris G. Cell Cycle. 2013 May 15;12(10):1616-24.Oocyte and embryo culture under oil profoundly alters effective concentrations of small molecule inhibitors.Rémillard-Labrosse G, Cohen S, Boucher É, Gagnon K, Vasilev F, Mihajlović AI, FitzHarris G.Front Cell Dev Biol. 2024 Mar 8;12:1337937. doi: 10.3389/fcell.2024.1337937.
THE KIT
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