Oral Presentation ESA-SRB-APEG-NZSE 2022

Personalized modelling of human infertility with human induced pluripotent stem cells   (#81)

Amander Clark 1
  1. University of California, Los Angeles, Los Angeles, CA, United States

Infertility is a disease that impacts around 8-10% of the reproductive age population around the world with around 30% of infertility cases being unexplained.  Human induced pluripotent stem cell (hiPSC) research enables reproductive diseases such as infertility to be studied when the reproductive status of the research participant is known. In this study, we consent research participants to undergo a procedure known as a skin punch biopsy to generate hiPSC lines following induced reprogramming using non-integrating sendai virus reprogramming technology.  Research participants in this study include individuals with proven fertility (live births without assisted reproductive intervention), individuals diagnosed with non-obstructive azoospermia (NOA), as well as individuals diagnosed with primary ovarian insufficiency (POI) including rare sets of monozygotic (MZ) twins with discordant POI.  Using various in vitro differentiate strategies, our group is currently assessing germ cell induction potential using hiPSC lines generated from each research participant as an individualized approach to understanding infertility in humans. Here, I will discuss our work on MZ twins discordant for the disease of POI, and the use of stem cell-based embryo models to understand germ cell induction and amnion specification.  For two of the MZ twin pairs in our study, gestational history indicates the twin pairs shared a single chorion (MC) and amnion (MA). Given germ cells are specified as the amnion forms, we hypothesized that MA twins discordant for POI arise through discordant allocation of germ cells from the single amnion.  Here we show that hiPSCs generated from MA twins with discordant POI induce equivalent numbers of germ cells when comparing the infertile twin’s cells to her fertile sister, as well as the ability of each twin’s cells to generate their own amniotic sac-like structure. Using these hiPSCs together with genome sequencing, our data suggests that the lack of germ cells in the infertile twin is not due to a genetic barrier to amnion or to germ cell formation.  Future studies will evaluate germ cell induction potential in the remaining research participants in order to increase our understanding of human infertility using the personalized approach of hiPSC-based modelling.