Preeclampsia (PE) is characterized by disturbed extravillous trophoblast migration toward uterine spiral arteries leading to increased uteroplacental vascular resistance and by vascular dysfunction resulting in reduced systemic vasodilatory properties. Its pathogenesis is mediated by an altered bioavailability of nitric oxide (NO) and tissue damage caused by increased levels of reactive oxygen species (ROS). Furthermore, superoxide (O₂⁻) rapidly inactivates NO and forms peroxynitrite (ONOO⁻). It is known that ONOO⁻ accumulates in the placental tissues and injures the placental function in PE. In addition, ROS could stimulate platelet adhesion and aggregation leading to intravascular coagulopathy. ROS-induced coagulopathy causes placental infarction and impairs the uteroplacental blood flow in PE. The disorders could lead to the reduction of oxygen and nutrients required for normal fetal development resulting in fetal growth restriction. On the other hand, several antioxidants scavenge ROS and protect tissues against oxidative damage. Placental antioxidants including catalase, superoxide dismutase (SOD), and glutathione peroxidase (GPx) protect the vasculature from ROS and maintain the vascular function. However, placental ischemia in PE decreases the antioxidant activity resulting in further elevated oxidative stress, which leads to the appearance of the pathological conditions of PE including hypertension and proteinuria. Oxidative stress is defined as an imbalance between ROS and antioxidant activity. This review provides new insights about roles of oxidative stress in the pathophysiology of PE.

The pathogenesis of preeclampsia begins when a fertilized egg infiltrates the decidua, resulting in implantation failure (e.g., due to extravillous trophoblast infiltration disturbance and abnormal spiral artery remodeling). Thereafter, large amounts of serum factors (e.g., soluble fms-like tyrosine kinase 1 and soluble endoglin) are released into the blood from the hypoplastic placenta, and preeclampsia characterized by multiorgan disorder caused by vascular disorders develops. Successful implantation and placentation require immune tolerance to the fertilized egg as a semi-allograft and the stimulation of extravillous trophoblast infiltration. Recently, exosomes with diameters of 50–100 nm have been recognized to be involved in cell–cell communication. Exosomes affect cell functions in autocrine and paracrine manners via their encapsulating microRNA/DNA and membrane-bound proteins. The microRNA profiles of blood exosomes have been demonstrated to be useful for the evaluation of preeclampsia pathophysiology and prediction of the disease. In addition, exosomes derived from mesenchymal stem cells have been found to have cancer-suppressing effects. These exosomes may repair the pathophysiology of preeclampsia through the suppression of extravillous trophoblast apoptosis and promotion of these cells’ invasive ability. Exosomes secreted by various cells have received much recent attention and may be involved in the maintenance of pregnancy and pathogenesis of preeclampsia.

It has been previously suggested that angiogenesis occurs during the menstrual cycle. Moreover, a rise in uterine blood flow is largely maintained by vasodilatation and substantial increases in angiogenesis. It is known that estradiol (E2) and progesterone (P4) are involved in angiogenesis. Recently, endothelial progenitor cells (EPCs) were found to be involved in neovascularization; however, their roles in uterine neovascularization have not been well characterized. We hypothesized that E2- or P4-mediated EPC proliferation plays important roles in uterine neovascularization during the menstrual cycle.

Globally, 2.6 million stillbirths occur every year. Of these, 98% occur in developing countries. According to the United Nations Children’s Fund, the neonatal mortality rate in Zambia in 2014 was 2.4%. In 2016, the World Health Organization released the International Classification of Diseases - Perinatal Mortality (ICD-PM) as a globally applicable and comparable system for the classification of the causes of perinatal deaths. However, data for developing countries are scarce. The aim of this study was to evaluate the rates and causes of stillbirths and neonatal deaths at a local hospital in Zimba, Zambia to identify opportunities for preventive interventions. All cases of stillbirths and neonatal deaths at Zimba Mission Hospital in Zambia in 2017 were included in this study. Outborn neonates who were transferred to the hospital and later died were also included in the study. Causes of stillbirths and neonatal deaths were analyzed and classified according to ICD-PM. In total, 1754 babies were born via 1704 deliveries at the hospital, and 28 neonates were transferred to the hospital after birth. The total number of perinatal deaths was 75 (4.2%), with 7 deaths in the antepartum, 25 deaths in the intrapartum, and 43 deaths in the neonatal period. Most antepartum deaths (n = 5; 71.4%) were classified as fetal deaths of unspecified causes. Intrapartum deaths were due to acute intrapartum events (n = 21; 84.0%) or malformations, deformations, or chromosomal abnormalities (n = 4; 16.0%). Neonatal deaths were related primarily to complications from intrapartum events (n = 19; 44.2%); low birth weight or prematurity (n = 16; 37.2%); or infection (n = 3; 7.0%). Perinatal deaths were associated with acute intrapartum events and considered preventable in 40 cases (53.3%). Effective interventions to prevent perinatal deaths are needed.