Welcome to the Medical and MolecularW Physiology Graduate ProgramW
at the
     

Institute for Biogenesis Research
Research Description

Monika A. Ward, Ph.D.
Assistant Professor

Phone:  (808) 956-0779
Fax:  (808) 956-7316
Email:  mward@hawaii.edu

Biomedical Tower, room E-104,
IBR Building, Manoa Campus

Ph.D. Biological Sciences (Reproductive Genetics), Institute for Human Genetics, Polish Academy of Sciences and Medical University of Poznan, Poland 2001

M.Sc. Biotechnology, Adam Mickiewicz University and Institute for Human Genetics, Polish Academy of Sciences, Poznan, Poland 1994

Sperm Genetics and Function in Fertilization

Intracytoplasmic sperm injection (ICSI) is the injection of a single spermatozoon directly into the cytoplasm of an oocyte using an injection pipette.  For the past decade, ICSI has been applied successfully in the treatment of infertile couples and is now widely used as a method of human assisted reproduction (ART).  In addition to its obvious role in overcoming the infertility, ICSI is also an excellent tool allowing exploring new venues of reproductive biology.  It provides a unique opportunity to examine the mechanisms underlying male infertility by looking into the reproductive potentials of individual spermatozoa.  The primary research interest of the lab is to study sperm genetics and function in fertilization with the use of ICSI combined with cytogenetic and molecular biology techniques, in a mouse model.  The overall goal is to determine how the genetic composition of sperm translates on its function in fertilization.  The ongoing projects involve: (1) reproducing infertile mice with phenotypes that mimic various human male infertility syndromes to test for ICSI effects; (2) studying sperm DNA damage and its mechanism and function in fertilization; (3) evaluating the function Y chromosome coded genes that are thought to be of importance for male fertility.

figure1
Teratozoospermia is a fertility defect expressed as an increased proportion of morphologically abnormal sperm that affects both humans and mice. Morphologically abnormal sperm (A) are often unable to fertilize oocytes rendering males infertile. Infertility can be overcome with ICSI (B). The resulting embryos can be tested for their potential to develop in vitro from zygote to blastocyst stage (C), genetic integrity (D, normal complement of paternal chromosomes visualized in the zygote) or in vivo development to live offspring (E). Such analyses provide evidence for the function of sperm from teratozoospermic males in assisted reproduction.

Selected Publications

1. Szczygiel M., Kurpisz M. 1999. Teratozoospermia and its effect on male fertility potential. Andrologia 31: 69-75. pdf

2. Szczygiel M., Kurpisz M. 2001. Chromosomal anomalies in human gametes and pre-implantation embyos, and their potential effect on reproduction. Andrologia 33: 294-265. pdf

3.  Kusakabe, H., Szczygiel, M.A., Whittingham, D.G. and Yanagimachi, R. 2001. Maintenance of genetic integrity in frozen and freeze-dried mouse spermatozoa. Proceedings of the National Academy of Sciences USA 98:13501-13506. pdf

4.  Szczygiel, M.A. and Ward, W.S. 2002. The combination of dithiothreitol and detergent treatment of spermatozoa causes paternal chromosomal damage. Biology of Reproduction 67:1532-1537. pdf

5.  Mohar, I., Szczygiel, M.A., Yanagimachi, R. and Ward, W.S. 2002. Sperm nuclear halos can transform into normal chromosomes after injection into oocytes. Molecular Reproduction and Development 62:416-420. pdf

6.  Szczygiel, M.A., Kusakabe, H., Yanagimachi, R. and Whittingham, D.G. 2002. Separation of motile populations of spermatozoa prior to freezing is beneficial for subsequent fertilization in vitro: A study with various mouse strains. Biology of Reproduction 67:287-292. pdf

7.  Szczygiel, M.A., Kusakabe, H., Yanagimachi, R. and Whittingham, D.G. 2002. Intracytoplasmic sperm injection is more efficient than in vitro fertilization for generating mouse embryos from cryopreserved spermatozoa. Biology of Reproduction 67:1278-1284. pdf

8.  Szczygiel, M.A., Moisyadi, S. and Ward, W.S. 2003. Expression of foreign DNA is associated with paternal chromosome degradation in ICSI-mediated transgenesis. Biology of Reproduction 68:1903-1910. pdf

9.  Ward, M.A., Kaneko, T., Kusakabe, H., Biggers, J.D., Whittingham, D.G. and Yanagimachi, R. 2003. Long term preservation of mouse spermatozoa after freeze-drying and freezing without cryoprotection. Biology of Reproduction 69:2100-2108. pdf

10.  Ward, M.A. and Ward, W.S. 2004. Functional aspects of mammalian sperm chromatic structure. Reproduction Fertility and Development 16:547-554. pdf

11.  Ward, M.A. 2005. ICSI effects in infertile azh mutant mice. Biology of Reproduction 73:193-200. pdf

12. Ward, M.A. and Burgoyne, P.S. 2006. The effects of deletions of the mouse Y chromosome long arm on sperm function - intracytoplasmic sperm injection (ICSI)-based analysis. Biology of Reproduction 74:652-658. pdf

13. Ajduk A., Yamauchi Y., Ward M.A. 2006: Sperm chromatin remodeling after intracytoplasmic sperm injection differs from that of in vitro fertilization. Biology of Reproduction 75: 442-451. pdf

14. Yamauchi, Y. and Ward M. A. 2007: Preservation of ejaculated mouse spermatozoa from fertile C57BL/6 and infertile Hook1/Hook1 mice collected from the uteri of mated females. Biology of Reproduction 76: 1002-1008. .pdf

15.  Riel J. M., Huang T. T. F., Ward M. A. 2007: Freezing-free preservation of human spermatozoa – a pilot study.  Archives of Andrology, 53: 275-284. .pdf

16. Yamauchi, Y., Ajduk, A, Riel J and Ward M. A. 2007: Ejaculated and epididymal mouse spermatozoa are different in their susceptibility to nuclease-dependent DNA damage and in their nuclease activity. Biology of Reproduction Jun 27; 77: 636-47. .pdf

17. Yasuhiro Yamauchi, Brendan Doe, Anna Ajduk, Ward M. A. : Genomic DNA damage in mouse transgenesis. Biology of Reproduction Jul 25; 77: 803-812. .pdf