Oxygen is an essential nutrient for cells. Oxygen is delivered to tissues via red blood cells through the vasculature. Molecular mechanisms mediating cellular responses to low oxygen tension have been identified. Hypoxia-inducible factors (HIFs) are activated by low oxygen and promote transcriptional regulation of downstream effector genes, which lead to cellular adaptations. Controlled hypoxia exposure is utilized as an experimental tool to investigate biological processes, regulating cellular adaptations. Here we describe detailed protocols for hypoxia exposure of pregnant rodent models and low oxygen exposure of trophoblast stem cells, utilizing gas-regulated chamber systems. The presentation also includes phenotypic analyses of the manipulated animal models and cells.