Daniel Rappolee

Background

About Daniel Rappolee

Our project started over 20 years ago, with stress effects on early post-fertilization mouse embryos in IVF culture and their component embryonic and placental trophoblast stem cells (ESC and TSC, respectively). Our lab developed an in vitro approach 8 years ago using high throughput screens (HTS) in stem cells to test for environmental and hormonal stresses that may cause miscarriage or birth defects. During early pregnancy, when most miscarriages occur, the embryo is simple. Soon after fertilization, the embryo is composed only of ESC and TSC. We use ESC and TSC with viable status reporters of stemness/differentiation/cell cycle status to report time and dose-dependent effects of stress hormones (cortisol), toxicants (phthalates, PFAS), and drugs (e.g, aspirin, retinoids) in HTS to test many single and mixed stress effects. For a small toxicant set, initial studies suggest that TSC are more sensitive and differentiate more stem cells than ESC (Puscheck et al, 2015 and 2022, from the Rappolee lab). We will test this hypothesis on a larger set of environmental and hormonal stressors. Understanding stress effects during pregnancy could be used to inform risk assessment decisions to make policy changes and increase pre- and postnatal health. It seems likely that embryos surviving this period of immense loss and miscarriage may survive some exposure to stress. Thus, a second important aspect of research on this development period is understanding the exposures and types of stress that do not cause embryo loss but cause stress that leads to postnatal effects. The 70% embryo loss is a massive issue in understanding environmental causes. Still, the 30% surviving embryos (e.g, many that developed and may be reading this blog!) are unlikely to have traversed early development without making some developmental (lineage imbalance) and epigenetic adaptations that affect health.