The placental pursuit for an adequate oxidant balance between the mother and the fetus

Abstract

The placenta is the exchange organ that regulates metabolic processes between the mother and her developing fetus. The adequate function of this organ is clearly vital for a physiologic gestational process and a healthy baby as final outcome. The umbilico-placental vasculature has the capacity to respond to variations in the materno-fetal milieu. Depending on the intensity and the extensity of the insult, these responses may be immediate-, mediate-, and long-lasting, deriving in potential morphostructural and functional changes later in life. These adjustments usually compensate the initial insults, but occasionally may switch to long-lasting remodeling and dysfunctional processes, arising maladaptation. One of the most challenging conditions in modern perinatology is hypoxia and oxidative stress during development, both disorders occurring in high-altitude and in low-altitude placental insufficiency. Hypoxia and oxidative stress may induce endothelial dysfunction and thus, reduction in the perfusion of the placenta and restriction in the fetal growth and development. This Review will focus on placental responses to hypoxic conditions, usually related with high-altitude and placental insufficiency, deriving in oxidative stress and vascular disorders, altering fetal and maternal health. Although day-to-day clinical practice, basic and clinical research are clearly providing evidence of the severe impact of oxygen deficiency and oxidative stress establishment during pregnancy, further research on umbilical and placental vascular function under these conditions is badly needed to clarify the myriad of questions still unsettled.

Keywords: high-altitude; hypoxia; oxidative stress; placenta; vascular dysfunction.

FIGURE 1

Vascular responses induced by hypoxia and oxidative stress. Hypoxia may increase ROS generation and induce (activate) transcription factors such as HIFs and NFκB. Consequently, the transcription of several genes is activated, inducing vasoconstriction and vascular remodeling. In addition, hypoxia and oxidative stress may induce endothelial dysfunction. All of the above impair vasodilatation capacity in the umbilico-placental vasculature and increases the risk of IUGR and miscarriage. ROS,: reactive oxygen species; HIFs, hypoxia inducible factors;, NFκB, nuclear factor-kappa B.

FIGURE 2

Theoretical depiction proposing the correlation of ROS, PO₂ and development of the placenta and the fetus. The intrauterine (utero-placental) ROS formation is a function of PO₂ in which, hypoxia supports elevations in ROS. Furthermore, the placental and fetal weights are closely related and dependent on increases in PO₂ and limitation of ROS. Changes in any of the four variables, may directly affect the potential maximum amount of the rest of the variables. For instance, a decrease in PO₂ may diminish fetal growth and term weight (IUGR). ROS, reactive oxygen species.