HYPOXIA AND REPRODUCTIVE HEALTH: Hypoxic regulation of preimplantation embryos: lessons from human embryonic stem cells

Abstract

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 highlight 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.

Using high throughput screens to predict miscarriages with placental stem cells and long‐term stress effects with embryonic stem cells

“…The greatest miscarriage rate is during early implantation, but the placental progesterone production does not replace luteal progesterone for another 5 weeks and hCG must increase exponentially during this period to maintain luteal progesterone and prevent embryo loss huESC are higher at 5% O 2 than 20% O 2 (current standard huESC/iPSC culture level): Oct4, Sox2, and Nanog. Functionally, growth rate and glycolysis (of huESC and embryos) and developmental potential (of human embryos) is higher at 5% >20% O 2 (Houghton, 2021).…”

Oxidative Stress and Assisted Reproduction: A Comprehensive Review of Its Pathophysiological Role and Strategies for Optimizing Embryo Culture Environment

“…AOX supplementation of culture media Early embryo development is not only reliant on the relevant nutrient supply, but is also crucially dependent on proper redox regulation in the different sections of the female genital tract [195]. Hence, attempts were made to reduce possible OS during the embryo culture by adding AOXs to the culture medium.…”

Molecular Regulation of Paused Pluripotency in Early Mammalian Embryos and Stem Cells

“…Preimplantation development takes place in a hypoxic environment, with intrauterine oxygen levels ranging from 1.5% in the rhesus monkey to 5.3% in rabbits and hamsters (Fischer and Bavister, 1993). The low-capacity oxidative phosphorylation mandated by hypoxia is further lowered during diapause, which may result in less oxidative DNA damage in the diapause embryo (Houghton, 2021). In addition, existing DNA damage may be more efficiently repaired during diapause.…”