Faculty Bio
Dr Anne Croy, Tier 1 Canada Research Chair in Reproduction, Development and Sexual Function.
Professor, Department of Biomedical and Molecular Sciences
Dr. Croy’s laboratory is now closed. She will not be offering future volunteer or research training opportunities.
Training
DVM (University of Guelph), Ph.D. (University of Toronto)
Research Interests
My research evaluates the functions, mechanisms of activation and lineage relationships of immune competent cell populations that home to the maternal-fetal interface during mammalian pregnancy. Of particular interest is the uterine Natural Killer lymphocyte, a mobile cell population that appears to promote changes to maternal arteries suppling the developing placentas. We conduct investigations using mice and women and create custom models involving adoptive transfer of lymphocytes, blastocysts and/or fetal trophoblast to immune deficient mice to advance basic understanding of this complex interface.
The role of immune cells in maternal hemodynamic changes over pregnancy, and in programming of the fetal cardiovascular system in normal and diabetic pregnancies are included in our assessments. Many women who experience pre-eclampsia during pregnancy are deficient in angiogenic factors, especially Placental Growth Factor (PGF), for weeks before developing clinical signs. From our studies of PGF deficient mice, we predicted that children born in a severe, preeclamptic pregnancy would have abnormal brain vascular development by MRI and combining the studies with anatomic and cognitive function testing protocols standardized by the NeuroDevNet Canadian Centers of Excellence program. The goals of our studies are to promote improved fetal and maternal health.
Sources of Research Funds: Natural Sciences and Engineering Research Council of Canada; Canada Foundation for Innovation and Canada Research Chairs Program, The Garfield Kelly Foundation and the Harry Botterell Foundation, Kingston General Hospital.
Selected Publications
B.A. Croy, A. T. Yamada, F. J. DeMayo and S. L. Adamson (Editors). The Guide to Investigation of Mouse Pregnancy. Reference Book of 808 pages. Academic Press/Elsevier. ISBN: 9780123944450. Epub Dec 24. Hard copy released Dec 31. Nominated by publisher for a 2015 PROSE Award, an annual recognition for the very best in professional and scholarly publishing. Publishers and authors are recognized at the Professional and Scholarly Publishers’ Annual Conference in Washington, D.C., for their commitment to pioneering works of research and for contributing to the conception, production, and design of landmark works in their fields.
R. L. Luna, V. R. Kay, M. T. Rätsep, K. Khalaj, M, Bidarimath, N. Peterson, A. Jin and B. A. Croy. Impact of Placental Growth Factor (PGF) deficiency on cerebral vascular development in mice. Submitted Jul 24.
A. M. Felker, Z. Chen, W. G. Foster, B.A. Croy. Receptors for non-MHC ligands contribute to uterine Natural Killer cell activation during pregnancy in mice. Placenta, 34(9):757-764. doi: 10.1016/j.placenta.2013.06.004. Epub 2013 Jun 24.
S. Leonard, P. D.A. Lima, B. A. Croy and C. L. Murrant. Gestational modification of murine spiral arteries does not reduce their drug-induced vasoconstrictive responses in vivo. Biology of Reproduction, 89 (6):139. doi: 10.1095.
P. D. A.Lima, M. Munir, M. Tu, A. R. Peng, B. A. Croy and A. Makrigiannis. Gestational impacts of Ly49 receptor knockdown in mouse uterine Natural Killer cells. Cellular and Molecular Immunology 11, (5) 467–476. Epub June 23, 2014; doi:10.1038/cmi.2014.44.
H. Amsalem, M. Kwan, A. Hazan, J. Zhang. R.L. Jones, W. Whittle, J. C. P. Kingdom, B. A. Croy, S. J. Lye and C. E. Dunk. Neutrophils are a novel angiogenic population in second trimester human decidua. Journal of Immunology, 193(6):3070-3079. Epub Aug 18.
K. L. Aasa, B. Zavan, R.L. Luna, P. G. Wang, N. M. Ventura, M. Y. Tse, P. Carmeliet, M. A. Adams, S. C. Pang and B. A. Croy. Placenta growth factor deficiency in mouse pregnancy has cardiovascular consequences. Biology of Reproduction. Epub Dec 23;biolreprod.114.124677
M. T. Rätsep, A. T. Yamada, P. Carmeliet, M. A. Adams and B. A. Croy. Placenta growth factor deficiency in the mouse conceptus alters decidual vascular structure. Placenta, 35(9):772-775. Epub July 17.
S. D. Burke, A. V. C. Seaward, S. Virani, M. Redhead, A. P. Hofmann, H. Ramshaw, G. N. Smith, B. A. Croy and P. D. A. Lima. Deviant homing receptor expression on blood CD56bright NK and NKT cells is present in pregnant type 1 diabetic women. PLoS ONE Mar 20;10(3):e0119526.
P. D. A. Lima, J. Zhang, C. Dunk, S. J. Lye and B. A. Croy. Leukocyte driven decidual angiogenesis in early pregnancy. Cellular and Molecular Immunology 11 (5) 522-537 ePub Jul 28. doi: 10.1038/cmi.2014.63
M. T Rätsep, A. M. Felker, V. R. Kay, L. Tolusso, M. L. Redhead, A. P. Hofmann and B. A. Croy. Uterine Natural Killer cells: Supervisors of vasculature construction in early decidua basalis. (invited review). Reproduction, 149(2):R91-R102, 2015. Epub Oct 2, 2014. pii: REP-14-0271
R. L. Luna, A. K. S. Nunes, A. G. V. Oliveira, S. M. R .Araujo, A. J. J. M. Lemos, S. W. S. Rocha, F.C.L. Maia, B. A. Croy and C.Peixoto. Sildenafil (Viagra®) blocks injury in LPS-induced mouse abortion: a potential therapeutic for acute pregnancy loss? in press, July 29.
B. A. Croy, Editorial Overview. Reproductive Immunology Issue One: Cellular and Molecular Biology. Cell Mol Immunol 11: 405-406; advance online publication, Epub July 28, 2014; doi:10.1038/cmi.2014.64.
B. A. Croy. Editorial Overview. Reproductive Immunology Issue Two: Cellular and Molecular Biology. Cell Mol Immunol 11: (6) in press.
A. P. Hofmann, B.A. Croy and S.A. Gerber.Uterine Natural Killer cells pace development of mouse decidua basalis. Mol. Human Reproduction, 2014 Jan;20(1):66-76. Epub Sept 3, doi: 10.1093/molehr/gat060
S. Leonard, P. D.A. Lima, B. A. Croy and C. L. Murrant. Gestational modification of murine spiral arteries does not reduce their drug-induced vasoconstrictive responses in vivo. Biology of Reproduction. 89(6):139. doi: 10.1095.
K. L. Aasa, K. K. Kwong, M. A. Adams and B. A. Croy. Analysis of maternal and fetal cardiovascular systems during hyperglycemic pregnancy in the Non-Obese Diabetic mouse. Biology of Reproduction. 2013 Jun 20;88(6):151. doi: 10.1095/biolreprod.112.105759
B. A. Croy, Z. Chen, A. P. Hofmann, E. M. Lord, A. L. Sedlacek and S. A. Gerber. Imaging of vascular development in early mouse deciduaand its association with leukocytes and trophoblasts. Biology of Reproduction, 87(5):125, 1-11. doi: 10.1095/biolreprod.112.102830. Epub. Sept 5.
P. D.A. Lima, K.Y.Degaki, C.Tayade, B. A. Croy and Á. T. Yamada. Heterogeneity in composition of mouse uterine Natural Killer cell granules. J. Leukocyte Biology92 (1): 195-204. ePub May 7. Cover image.
Z. Chen, J. Zhang, K. Hatta, P.D.A. Lima, H. Yadi, F. Colucci, A.T. Yamada and B.A. Croy. DBA-lectin reactivity defines function-biased mouse uterine natural killer cell subsets. Biology of Reproduction 87(4):81. doi: 10.1095/biolreprod.112.102293. Epub Aug.8. Cover image.
V. Barrette, M.A. Adams and B.A. Croy. Endometrial decidualization does not trigger the blood pressure decline of normal early pregnancy in mice. Biology of Reproduction. 86(3):1-5, with accompanying commentary. Epub Dec. 7, 2011.
B.A. Croy, S.D. Burke, V. Barrette, J. Zhang, K. Hatta, G.N. Smith, J. Bianco, A.T. Yamada and M.A. Adams. Identification of the primary outcomes that result from deficient spiral arterial modification in pregnant mice. (Invited paper). Pregnancy Hypertension. 1:87-94. Epub Nov 25, 2010.
S.D. Burke, V. Barrette, J. Bianco, J.G. Thorne, A.T. Yamada, S.C. Pang, M.A. Adams and B.A. Croy. Patterns of blood pressure regulation during murine pregnancy. Hypertension. 55:(3):729-37. Epub January 10.
J.H. Zhang, A. T. Yamada and B.A. Croy. DBA-lectin reactivity defines natural killer cells that have homed to mouse decidua. Placenta. 30:968-973.
B.A. Croy and S.P. Murphy (Guest Eds) Fetal-Maternal Immunology. Immunol Invest 2008 Thematic Issue. Volume 37 Issue 5.
B.A. Croy, H. He, S. Esadeg, Q. Wei, D. McCartney, J. Zhang, A. Borzychowski, A.A. Ashkar, G.P. Black, S.S. Evans, S. Chantakru, M. van den Heuvel, V.A. Paffaro Jr. and A.T. Yamada. Uterine natural killer cells: Insights to their cellular and molecular biology from mouse modelling (invited review). Reproduction 126: 149-160.
A.A. Ashkar, G.P. Black, Q. Wei, H. He, L. Liang, J.R. Head and B.A. Croy. Assessment of requirements for IL-15 and IRFs in uterine natural killer cell differentiation and function during pregnancy. J. Immunol. 171: 2937-2944.
H. Engelhardt, B.A. Croy and G.J. King. Evaluation of Natural Killer cell recruitment to embryonic attachment sites during early porcine pregnancy. Biol. Reprod. 66: 1185-1192.
S. Chantakru, C. Miller, L.E. Roach, W.A. Kuziel, N. Maeda, W-C. Wang, S.S. Evans and B.A. Croy. Analysis of contributions from lymphocyte self-renewal and trafficking to the uterine Natural Killer cell population of early pregnancy. J. Immunol. 168: 22-28.
A. Ashkar, J.P. Di Santo and B.A. Croy. Interferon-γ contributes to initiation of uterine vascular modification, decidual integrity and uterine NK cell maturation during normal murine pregnancy. J. Exp. Med. 192: 259-270 with accompanying Editorial Commentary F1-F4.
J. Greenwood, K. Minhas, J.P. Di Santo, Y. Kiso, M. Makita and B.A. Croy. Ultrastructural studies of implantation sites from mice deficient in uterine natural killer cells. Placenta. 21: 693-702.
B.A. Croy. Hasn’t the time come to replace the term Metrial Gland? J. Reprod. Immunol. 42: 127-129.
J. Guimond, B. Wang and B.A. Croy. Engraftment of NK cells reverses the reproductive deficits in pregnancy NK cell and T cell deficient Tgε26 mice. J. Exp. Med. 187: 217-223.
P. Piotrowski and B.A. Croy. Maternal cells are widely distributed in murine fetuses during normal pregnancy. Biol. Reprod. 54: 1103-1110.
B.A. Croy, C.M. Stewart, B-A. McBey and Y. Kiso. An immunohistologic analysis of murine uterine T cells between birth and puberty. J. Reprod. Immunol. 23: 223-233.
B.A. Croy and Y. Kiso. Granulated metrial gland cells: an NK cell subset of the pregnant murine uterus. Microscopy Review and Technique (invited review) 25: 189-200.
B.A. Croy and A.J.S. Summerlee. Intracerebroventricular administration of a single small dose of IL-1β is sufficient to initiate murine pregnancy failure. Res. in Immunol. 141: 195-201.
B.A. Croy, A. Waterfield, W. Wood and G.J. King. Normal murine and porcine embryos recruit NK cells to the uterus. Cell. Immunol. 115: 471-480.
B.A. Croy, P. Gambel, J. Rossant and T.G. Wegmann. Characterization of murine decidual NK cells and their relevance to the success of pregnancy. Cell. Immunol. 93: 315-326.
J. Rossant, V.M. Mauro and B.A. Croy. Importance of trophoblast genotype for survival of interspecific murine chimeras. J. Exp. Embryo. Morph. 69: 141-149.
Published Abstracts:
M.L. Redhead, B.A. Croy. The transcription factor NFIL3 is not required for uNK cell differentiation but contributes to uNK cell functions. 35th meeting, Am. Soc. Reproductive Immunology, Kingston ON Jun 2-5
B.A. Croy, M.T. Rätsep, V.R. Kay, R. L. Leal, B. Zavan, B. Maser, A. Hickman, G.N. Smith, J.N. Reynolds1, A.Paolozza, P.W. Stroman, J.G. Sled, C. Beaulieu, D. Zhou and N.D. Forkert. Journeying from Reproductive Immunology to Children’s Brains. Presidential Symposium Address, Am. Soc. Reproductive Immunology, Kingston ON Jun 2-5
B.A. Croy. Uterine Natural Killer Cells: Special enhancers of pregnancy quality. 1st Nature Immunology-Cellular and Molecular Immunology Joint Conference on “Inflammation, Stress and Immune Homeostasis”, Hefei, China June 17-19 (Invited Plenary Address)
M.T. Rätsep and B.A. Croy. Impact of Placental Growth Factor and preeclampsia on brain development, cognition, and behaviour. Int. Fed. Placental Associations, Brisbane Aust. Sept 8th – 11th. Podium Address for Top Trainee Abstract from 2014 meeting.
Lab
Dr. Croy’s laboratory is now closed. She will not be offering future volunteer or research training opportunities.