Oxygen, the Janus gas; its effects on human placental development and function

Abstract

The accumulation of oxygen in the earth's atmosphere enabled metabolic pathways based on high‐energy electron transfers that were capable of sustaining complex multicellular organisms to evolve. This advance came at a price, however, for the high reactivity of oxygen posed a major challenge as biological molecules became susceptible to oxidative damage, resulting in potential loss of function. Many extant physiological systems are therefore adapted, and homeostatically regulated, to supply sufficient oxygen to meet energy demands whilst also protecting cells, and mitochondria in particular, from excessive concentrations that could lead to oxidative damage. The invasive form of implantation displayed by the human conceptus presents particular challenges in this respect. During the first trimester, the conceptus develops in a low oxygen environment that favours organogenesis in the embryo, and cell proliferation and angiogenesis in the placenta. Later in pregnancy, higher oxygen concentrations are required to support the rapid growth of the fetus. This transition, which appears unique to the human placenta, must be negotiated safely for a successful pregnancy. Normally, onset of the maternal placental circulation is a progressive periphery‐centre phenomenon, and is associated with extensive villous regression to form the chorion laeve. In cases of miscarriage, onset of the circulation is both precocious and disorganized, and excessive placental oxidative stress and villous regression undoubtedly contribute to loss of the pregnancy. Comparison of experimental and in vivo data indicates that fluctuations in placental oxygen concentration are a more powerful stimulus for the generation of oxidative stress than chronic hypoxia alone. Placental oxidative and endoplasmic reticulum stress appear to play key roles in the pathophysiology of complications of pregnancy, such as intrauterine growth restriction and preeclampsia, through their adverse impacts on placental function and growth. Establishing an inviolable maternal blood supply for the second and third trimesters is therefore one of the most crucial aspects of human placentation.

Shown for reading. Its publisher allows quoting it, not republishing it.

Cited by papers we hold 12

• The Impact of Hypoxia in Early Pregnancy on Placental Cells · 2021
  No notice
• Integrated Systems Biology Approach Identifies Novel Maternal and Placental Pathways of Preeclampsia · 2018
  No notice
• Implication of Oxidative Stress in Fetal Programming of Cardiovascular Disease · 2018
  No notice
• Impaired functional capacity of fetal endothelial cells in preeclampsia. · 2017
  Not checked
• Angiogenesis in the Placenta: The Role of Reactive Oxygen Species Signaling · 2015
  No notice
• Oxidative Stress in Placenta: Health and Diseases · 2015
  No notice
• Hypoxic stress induces, but cannot sustain trophoblast stem cell differentiation to labyrinthine placenta due to mitochondrial insufficiency · 2014
  Not checked
• The Role of microRNAs in Mitochondria: Small Players Acting Wide · 2014
  No notice
• The effect of hypoxia on facial shape variation and disease phenotypes in chicken embryos · 2013
  Not checked
• Suppression of Mitochondrial Electron Transport Chain Function in the Hypoxic Human Placenta: A Role for miRNA-210 and Protein Synthesis Inhibition · 2013
  Corrected
• Impact of Oxidative Stress in Fetal Programming · 2012
  No notice
• Soluble Flt-1 and PlGF: new markers of early pregnancy loss? · 2011
  Not checked

Reads

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.