• Ma, Sai

    Titles

    Investigator, BC Children's Hospital
    Associate Professor, Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of British Columbia

    Degrees / Designations
    PhD
    Primary Area of Research
    Healthy Starts
    Secondary Area(s) of Research
    Phone
    604-875-2591
    Fax
    604-875-2722
    Lab Phone
    Mailing Address

    BC Women's Hospital & Health Centre
    C-4500 Oak Street
    Vancouver, BC V6H 3N1

    Affiliate Websites
    Research Areas
    • Assisted reproductive technologies (ART)
    • Genetic and epigenetic aspects of male factor infertility
    • Outcome of ART pregnancies
    Summary

    The tools of assisted reproductive technologies (ART) have catalyzed remarkable developments in reproductive medicine. As a result, over five million babies have been born worldwide using ART since the first live birth derived from in vitro fertilization (IVF) in 1978. The prevalence of ART is largely a consequence of the high frequency of couples experiencing fertility difficulties (~15%) that can be treated by ART.

    Our research goals are focused on genetic epigenetic investigations, at multiple levels of human development, related to the reproductive health of couples undergoing ART. My overall research program has been dedicated to understanding the roles genetics and epigenetics play in male infertility as well as in the negative outcomes of pregnancies derived from ART.

    The objectives of my research program are diverse and include: (1) the identification and analysis of meiotic errors and its association with sperm aneuploidy and male infertility, and epigenetic modifications in male infertility; (2) the definition of the basal level of chromosomal abnormalities in pre-implantation embryos, and differentiation of the roles of meiotic and mitotic abnormalities in implantation failure in ART; (3) the examination of the potential genetic and epigenetic risks associated with ART pregnancies that may offer opportunities to develop unique strategies to prevent abnormal pregnancies after ART.

    Current Projects

    Investigation of meiotic and imprinting defects as an underlying cause of male factor infertility:

    Infertility is regarded as a major health problem, affecting approximately one in six couples in Canada. It is estimated that 30-40% of couples seeking fertility treatments are diagnosed with male-factor infertility due to abnormal sperm production. In the majority of these cases, the cause of infertility remains unknown. It is suspected that genetic and epigenetic factors may both play an important role in the onset of male infertility. Recent ours and other studies have shown that errors in this meiotic division are more prevalent in infertile men and may play an important role in idiopathic male infertility. We recently provided evidence that meiotic errors in infertile men may also be associated with the production of aneuploid sperm, that is, sperm containing either extra or missing chromosomes. There is increasing evidence in the literature to suggest that infertile men may be at risk of having abnormal DNA methylation (a chemical modification of genetic sequences) in their sperm, which may affect sperm production. Recently, we also found that a subgroup of infertile men had increased imprinting defects (defects in the methylation of specific DNA sequences) in their sperm. We will use recently developed techniques to further characterize the meiotic defects that lead to the production of aneuploid sperm and male infertility in two unique infertile male groups (men with very low sperm counts with and without chromosome rearrangements). We will also investigate the prevalence of imprinting defects among infertile men, and its possible association with meiotic errors within the same study population. Detailed meiotic and imprinting studies of infertile men will begin to reveal the underlying genetic causes of male infertility. The results of this study could lead to improved treatment and reproductive outcomes for couples undergoing infertility treatments, such as intracytoplasmic sperm injection (ICSI). 

    Study of chromosomal and epigenetic abnormalities after ICSI treatment for male infertility:

    Intracytoplasmic sperm injection (ICSI) is an assisted reproductive procedure in treatment of male infertility. It involves the injection of a sperm into an oocyte to facilitate fertilization. Because natural barriers to fertilization are bypassed, ICSI may facilitate the transmission of genetic (DNA related) and epigenetic (DNA independent mechanisms that influence gene expression) abnormalities to the next generation. These abnormalities include a deviation from the normal complement of chromosomes (46 units of compacted DNA) in a cell. There is also concern that the injection procedure of ICSI disrupts the organization of the oocyte and this may affect the development of the resulting embryo. These alterations in pregnancies can potentially lead to pregnancy loss, birth defects, and low birth weight. We hypothesize that ICSI presents both procedure-dependent and independent risks to the fetus. We will investigate of the incidence of chromosomal abnormalities and epigenetic changes in the pregnancies of three assisted reproductive techniques - intrauterine insemination, in vitro fertilization (IVF), and ICSI - and evaluate how the differences among the techniques, namely the use of cell culture, the genetic background of different types of infertility involved, and the method of fertilization, effects the development of these abnormalities. Furthermore, we will examine key steps of cell division in the development of sperm when a chromosomal abnormality in a child is determined to be passed on from the father. Our long-term aims are to identify chromosomal and epigenetic risk factors to conceptions of ICSI, and to develop strategies to prevent abnormal offspring from being born after ICSI.

    Selected Publications

    Ren H, Chow V, Ma S. Meiotic behaviour and sperm aneuploidy in an infertile man with a mosaic 45,X/46,XY karyotype. Reprod Biomed Online 31(6):783-789 (2015) PMID: 26511872

    Sakian S, Louie K, Wong EC, Havelock J, Kashyap S, Rowe T, Taylor B, Ma S. Altered gene expression of H19 and IGF2 in placentas from ART pregnancies.  Placenta  36:1100-1105 (2015) PMID: 26386650  

    Kirkpatrick G, Ren H, Liehr T, Chow V, Ma S. Meiotic and sperm aneuploidy studies in three carriers of Robertsonian translocations and small supernumerary marker chromosomes. Fertil Steril 103:1162-1169 (2015) PMID: 25796321

    Wu EX, Stanar P, Ma S. X-chromosomal inactivation in female newborns conceived by assisted reproductive technologies. Fertil Steril 101:1718-1723 (2014) PMID: 24726222

    Wilson AD, Wu EX, Chan Wong E, Havelock J, and Ma S. Maternal origin of 47, XXY and confined placental mosaicism 47,XXY/48,XXY,+13 in an infant conceived through IVF. J Assist Reprod Genet.  30; 807-182 (2013) PMID: 23624985

    Chan Wong E, Hatakeyama C, Minor A, Ma S. Investigation of confined placental mosaicism by CGH in IVF and ICSI pregnancies. Placenta 33: 202-206 (2012) PMID: 22239762

    Kirkpatrick G and Ma S. Meiotic segregation and interchromosomal effects in a rare (1:2:10) complex chromosomal rearrangement. J Assist Reprod Genet 29: 77-81 (2012) PMID: 22105185 

    Kirkpatrick G, Chow V, Ma S. A systematic study of meiotic recombination, synapsis, meiotic inactivation and sperm aneuploidy in a carrier with chromosome 1 inversion. Reprod BioMed Online 24: 91-100 (2012) PMID: 22116071

    Chan Wong E, Hatakeyama C, Minor A, Ma S. DNA methylation at H19 /IGF2 ICR1 in the placenta of SGA pregnancies conceived by IVF and ICSI.  Fertil Steril 30: 2524-2526 (2011) PMID: 21704210

    Minor A, Chow V, Ma S. Aberrant DNA methylation at imprinted genes in testicular sperm retrieved from men with obstructive azoospermia and post vasectomy reversal. Reproduction 141:749-57 (2011) PMID: 21389080

    Tang S, Gao HJ, Zhao Y, Ma S. Aneuploidy and DNA fragmentation in morphologically abnormal sperm.  Int Int J Androl.  33: e163-79 (2010) PMID: 19732195

    Ferguson K, Leung S, Jiang D, Ma S. Distribution of MLH1 foci and inter-focal distances in spermatocytes of infertile men. Hum Reprod 24: 1313-1321 (2009) PMID: 19246465

    Kirkpatrick G, Ferguson KA, Gao H, Tang S, Chow V, Ho Yuen B, Ma S. A comparison of sperm aneuploidy rates between infertile men with normal and abnormal karyotypes.  Hum Reprod 23: 1679-1683 (2008). PMID: 22137696 

    Ferguson K, Chow V, Ma S. Silencing of unpaired meiotic chromosomes and altered recombination patterns in an azoospermic carrier of a t(8;13) reciprocal translocation. Hum Reprod 23: 988-995 (2008). PMID: 18270180

    Chan Wong E, Ferguson  K, Chow V, Ma S. Sperm aneuploidy and meiotic status of an XYY infertile man.  Hum Reprod 23: 374-378 (2008). PMID: 18037669 

    Vincent RN, Gooding LD, Louie K, Chan Wong E, Ma S. Altered DNA methylation and expression of PLAGL1 in cord blood from assisted reproductive technology pregnancies compared with natural conceptions. Fertil Steril. 2016 Sep 1 PMID: 27178226 

    Ren H, Ferguson K, Kirkpatrick G, Vinning T, Chow V, Ma S. Altered Crossover Distribution and Frequency in Spermatocytes of Infertile Men with Azoospermia. PLoS One. 2016 Jun 6 PMID: 27273078

    Grants
    Honours & Awards

     

    Research Group Members

    • Annie Ren - Graduate Student
    • Kate Watt - Graduate Student
    • Kenny Louie - Graduate Student
    • Luke Gooding - Graduate Student
    • Richard Ng - Graduate Student
    • Samuel Schafer - Graduate Student
    • Ei-Xia Mussai - Graduate Student