Hypoxic regulation of preimplantation embryos: lessons from human embryonic stem cells

Development of the preimplantation embryo is reliant on nutrients present in the milieu of the reproductive tract. While carbohydrates, amino acids, lipids, and micronutrients are often considered when discussing preimplantation embryo nutrition, environmental oxygen is frequently overlooked. Although oxygen is not classically considered a nutrient, it is an important component of the in vitro culture environment and a critical regulator of cellular physiology. Oxygen is required to sustain an oxidative metabolism but when oxygen becomes limited, cells mount a physiological response driven by a family of transcription factors termed 'hypoxia inducible factors' which promote expression of a multitude of oxygen sensitive genes. It is this hypoxic response that is responsible not only for the switch to a glycolytic metabolism but also for a plethora of other cellular responses. There has been much debate in recent years over which environmental oxygen tension is preferential for the culture of preimplantation embryos. The review will evaluate this question and highlights how research using human embryonic stem cells can inform our understanding of why culturing under physiological oxygen tensions may be beneficial for the development of embryos generated through clinical in vitro fertilisation.

Automated summary

The development of preimplantation embryos relies on various nutrients in the reproductive tract, including oxygen which plays a crucial role in cellular physiology. Inadequate oxygen triggers a hypoxic response leading to a switch to glycolytic metabolism in cells, with ongoing debate about the optimal oxygen tension for embryo culture. Research using human embryonic stem cells can help understand the benefits of culturing embryos under physiological oxygen tensions.