The Importance of Metabolic and Environmental Factors in the Occurrence of Oxidative Stress during Pregnancy

Abstract

Metabolic changes in pregnant women begin in the first weeks after conception under the influence of placental hormones that affect the metabolism of all nutrients. An increased concentration of total lipids accompanies pregnancy and an increased accumulation of triglycerides in low-density lipoproteins (LDL) particles. Lipids in small dense LDL particles are more susceptible to oxidative modification than normal-density LDL particles. Unlike LDL high-density lipoproteins (HDL), lipoprotein particles have an atheroprotective role in lipid metabolism. The very growth of the fetus depends on the nutrition of both parents, so obesity is not only in the mother but also in the father. Nutritional programming of the offspring occurs through changes in lipid metabolism and leads to an increased risk for cardiometabolic diseases. Pregnancy is accompanied by an increased need for oxygen in the mitochondria of the placenta and a tendency to develop oxidative stress. Oxidative stress represents a disturbance in the balance of oxidation-reduction processes in the body that occurs due to the excessive production of free oxygen radicals that cellular homeostatic mechanisms are unable to neutralize. When the balance with the antioxidant system is disturbed, which happens when free oxygen radicals are in high concentrations, serious damage to biological molecules occurs, resulting in a series of pathophysiological and pathological changes, including cell death. Therefore, oxidative stress plays a significant role in the pathogenesis of many complications that can occur during pregnancy. The oxidative status of pregnant women is also influenced by socioeconomic living conditions, lifestyle habits, diet, smoking, and exposure to environmental air pollution. During a healthy pregnancy, the altered lipid profile and oxidative stress create an increased risk for premature birth and pregnancy-related diseases, and a predisposition to adult diseases.

Keywords: diseases; lipid metabolism; oxidative stress; pregnancy.

Figure 1

Lipid metabolism during a healthy pregnancy. Total cholesterol and triglycerides increase significantly already in early pregnancy and continue to increase during pregnancy, so that by the end of pregnancy cholesterol increases by about 30% and triglycerides almost three times. The values of LDL and HDL cholesterol also change during pregnancy, while the values of apolipoprotein AI (ApoAI) and apolipoprotein B (ApoB) during pregnancy generally follow the values of the lipoprotein particles in which they are composed, ApoAI in the composition of HDLa and ApoB in the composition of LDLa. A specific characteristic of this altered lipid profile during physiological pregnancy is an increase in the value of HDL cholesterol, which has an atheroprotective effect. This characteristic distinguishes hyperlipidemia of physiological pregnancy from pathological dyslipidemia, which is responsible for the onset of atherosclerosis towards the end of pregnancy, when the proatherogenic components (cholesterol, triglycerides, ApoB, LDL) continue to increase, while the HDL value does not increase but remains close to the level of the second trimester, even with the tendency for a slight decrease in value, and this may also mean its reduced antioxidant and anti-inflammatory functionality, which further points to different mechanisms responsible for the development of atherosclerosis. The fact that HDL increases during pregnancy and reaches a maximum in the second trimester suggests the possibility of other adaptive and protective mechanisms involved in late pregnancy. After childbirth, the changed lipid profile is maintained for a long period, which can be up to a year or more. The value of HDL in the cumulative effects of multiple pregnancies remains permanently lower, which also represents a risk for developing cardiovascular diseases in a woman’s later life.

Figure 2

Formation of free radicals. In a damaged antioxidant environment, hydroxyl ion (OH•) is formed. The hydroxyl ion is highly reactive and its half-life is about 10–9 s. Due to its high reactivity, it reacts with every biological molecule that is in its immediate vicinity. The most common causes for free radicals in pregnancy are smoking, air pollution, ultraviolet radiation, and ionizing radiation; physiologically altered metabolism during pregnancy can lead to mitochondrial damage and DNA damage.