JI Program: Exploratory (Ob/Gyn)
Status: Active/ Ongoing
The incidence of human embryo aneuploidy (abnormal number of chromosomes) is more prevalent than other mammals and the primary cause of spontaneous miscarriages, congenital birth defects and infertility. Infertility affects 1 in 6 reproductive age couples in the United States, China, and Worldwide. While success in treating infertility has increased over the last 3 decades, the current National/International average success in having a baby with Assisted Reproductive Technologies (ARTs), like In Vitro Fertilization (IVF), is ~35% across all maternal ages. In addition, this average IVF-live birth success declines dramatically in women older than 37 years of age. This is believed to be caused by increased frequency of oocyte meiotic non-disjunctions in the first and second oocyte meiotic divisions prior to embryo development. In the last decade significant efforts have been applied to improve clinical ART success rates by performing genetic analysis of the human pre-implantation embryo.
Experiments proposed in the study utilize individual and collaborative strengths of the Smith lab at University of Michigan / MStem Cell Lab and the Qiao lab at Peking University Health Science Center. The Smith lab will bring well-established regulatory compliance and implementation of human embryo donation for human embryonic stem cell derivation and research. The Smith lab also brings extensive expertise in human pre-implantation embryogenesis, micromanipulation, human embryo outgrowth, and human embryonic stem cell derivation and analysis. The Qiao lab will bring vast experience also in human embryology, and importantly in single-cell genetic analysis and state-of-the-art genetic sequencing and bioinformatics. Collectively, data generated through this mutually beneficial inter-university collaboration will begin to provide basic information about early human embryo cell specification, genetic stability of mosaicism during early human embryo development, mechanistic causes of congenital aneuploidies, and practical information about safety and efficacy of clinical pre-implantation genetic screening.
- 1 faculty member and 1 PhD student from PKUHSC received extensive training for 1 year and 3 months respectively at Dr. Smith's lab in U-M. Specific training received includes: embryo vitrification/ warming, embryo biopsy, embryo plating, initiation of hESC derivation, hESC expansion.
- PKUHSC visiting scholars shared expertise in single cell isolation, and MALBAC whole genome amplification, resulting in standardized protocols in both areas at U-M.
- Dr. Gary Smith visited PKUHSC in January 2018 and April 2019, with successful data assessment and discussion with the PKUHSC team.
- An abstract (which resulted in an oral presentation) was submitted and accepted at the American Society of Reproductive Medicine (ASRM) meeting in Denver, October 2018.
- U-M team invited the PKUHSC PI, Professor Jie Qiao, to be a presenter at the International Meeting on Genetics of Assisted Reproductive Technologies, where Dr. Smith also presented preliminary findings from the JI collaborative project.
- PKUHSC is developing additional bioinformatics/ in silico assessment protocols determining copy number variance (CNV).