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.

Adverse effects of perinatal nicotine exposure on reproductive outcomes

“…Although maternal tobacco use has been shown to increase markers of oxidative stress in the placenta (Sbrana et al 2011), in vivo and in vitro studies have failed to find evidence of oxidative damage or increased ROS production in trophoblast cells following nicotine administration , Repo et al 2014, Lo et al 2015. Interestingly, placentas from nicotinetreated animals exhibit evidence of hypoxia, which has been demonstrated to increase ROS production (Herrera et al 2014). Consistent with this observation, nicotine treatment decreased local and circulating endocrine gland-derived vascular endothelial growth factor (EG-VEGF) in vivo and in vitro, a key placental angiogenic factor (Brouillet et al 2012.…”

“…Under conditions of prolonged oxidative stress, the unstable reactivity of excessive ROS can lead to free radical damage in DNA, proteins, carbohydrates, and lipids, and eventually, mitochondrial-mediated apoptosis and cell death (Cao & Kaufman 2014, Chaudhari et al 2014. Increased oxidative stress has been demonstrated to impair placental development and function as well as cause damage to oocytes, sperm, and embryos (Agarwal et al 2008, Herrera et al 2014, thus it is thought to underlie many aspects of impaired reproductive health (Agarwal et al 2012, Agarwal et al 2014, Dai et al 2015.…”

Epigenetic Programming of Cardiovascular Disease by Perinatal Hypoxia and Fetal Growth Restriction

“…In the earlier stages, limitations in oxygen supply promote trophoblast proliferation; however, persistence in a hypoxic environment as occurs in FGR harms trophoblast invasion and the transformation of spiral arteries leading to a vascular dysfunction of the placenta and impaired fetal growth. Thus, chronic hypoxia and oxidative stress have an important role in the placental dysfunction observed in FGR [15]. Several studies on humans confirm the presence of molecular markers of oxidative stress in the FGR placentae, the fetus, and the mother [16][17][18][19].…”

“…Presently, oxygen, glucose, free radicals, amino acids, and hormones have been shown to play an important role in modulating fetal growth and development. These factors are dynamically regulated throughout gestation [15]. In the earlier stages, limitations in oxygen supply promote trophoblast proliferation; however, persistence in a hypoxic environment as occurs in FGR harms trophoblast invasion and the transformation of spiral arteries leading to a vascular dysfunction of the placenta and impaired fetal growth.…”

“…In both cases (chick embryos and mammalian fetuses), the presence of endothelial dysfunction and vascular remodeling is observed mainly in peripheral arteries. The mechanism by which hypoxia induces cell damage in either case is the result of an increased generation of reactive oxygen species (ROS) due to an incomplete reduction of oxygen [15,32].…”