Medicine and Health Sciences Commons^™

Hypoxic Stress Induces, But Cannot Sustain Trophoblast Stem Cell Differentiation To Labyrinthine Placenta Due To Mitochondrial Insufficiency, Yufen Xie, Sichang Zhou, Zhongliang Jiang, Jing Dai, Elizabeth E. Puscheck, Icksoo Lee, Graham Parker, Maik Hüttemann, Daniel A. Rappolee

Department of Obstetrics and Gynecology Research Publications

Dysfunctional stem cell differentiation into placental lineages is associated with gestational diseases. Of the differentiated lineages available to trophoblast stem cells (TSC), elevated O2 and mitochondrial function are necessary to placental lineages at the maternal–placental surface and important in the etiology of preeclampsia. TSC lineage imbalance leads to embryonic failure during uterine implantation. Stress at implantation exacerbates stem cell depletion by decreasing proliferation and increasing differentiation. In an implantation site O2 is normally ~ 2%. In culture, exposure to 2% O2 and fibroblast growth factor 4 (FGF4) enabled the highest mouse TSC multipotency and proliferation. In contrast, hypoxic stress (0.5% …