Grant Project Title:
Human Embryo Mosaicism: Towards Understanding Longitudinal and Developmental Genetic Concordance Between Embryonic Trophectoderm, Inner Cell Mass, and Stem Cells
Our hypothesis is that blastocyst regional cell genetic concordance is low, embryonic mitotic segregation errors are frequent, and that collectively, these biological factors contribute to embryonic mosaicism and limitations in predicting offspring genetic normalcy. This hypothesis is being addressed with two specific aims: 1) to elucidate regional genetic concordance/discordance within human preimplantation blastocysts trophectoderm, inner cell mass, and resulting human embryonic stem cells with single cell-sequencing; and 2) to quantify the incidence of age-related human oocyte/embryo meiotic and mitotic nondisjunctions as they contribute to blastocyst mosaicism.
These studies represent first-in-field approaches to systematically and longitudinally identify developmental and genetic events in human embryos that must be understood to allow confidence in preimplantation genetic testing-aneuploidy (PGT-A) use and interpretations. These data will guide the future of PGT-A and have an immediate impact of eliminating knowledge-gaps in PGT-A, mosaicism, and decision-making for reproductive healthcare providers, patients, and the general population.
Gary D. Smith, Ph.D., H.C.L.D.
Professor of Ob/Gyn, Physiology, and Urology
Director of MStem Cell Lab
Director of Reproductive Sciences Program
University of Michigan