Preeclampsia: From Cellular Wellness to Inappropriate Cell Death, and the Roles of Nutrition

Abstract

Preeclampsia is one of the most common obstetrical complications worldwide. The pathomechanism of this disease begins with abnormal placentation in early pregnancy, which is associated with inappropriate decidualization, vasculogenesis, angiogenesis, and spiral artery remodeling, leading to endothelial dysfunction. In these processes, appropriate cellular deaths have been proposed to play a pivotal role, including apoptosis and autophagy. The proper functioning of these physiological cell deaths for placentation depends on the wellbeing of the trophoblasts, affected by the structural and functional integrity of each cellular component including the cell membrane, mitochondria, endoplasmic reticulum, genetics, and epigenetics. This cellular wellness, which includes optimal cellular integrity and function, is heavily influenced by nutritional adequacy. In contrast, nutritional deficiencies may result in the alteration of plasma membrane, mitochondrial dysfunction, endoplasmic reticulum stress, and changes in gene expression, DNA methylation, and miRNA expression, as well as weakened defense against environmental contaminants, hence inducing a series of inappropriate cellular deaths such as abnormal apoptosis and necrosis, and autophagy dysfunction and resulting in abnormal trophoblast invasion. Despite their inherent connection, the currently available studies examined the functions of each organelle, the cellular death mechanisms and the nutrition involved, both physiologically in the placenta and in preeclampsia, separately. Therefore, this review aims to comprehensively discuss the relationship between each organelle in maintaining the physiological cell death mechanisms and the nutrition involved, and the interconnection between the disruptions in the cellular organelles and inappropriate cell death mechanisms, resulting in poor trophoblast invasion and differentiation, as seen in preeclampsia.

Coenzyme A Restriction as a Factor Underlying Pre-Eclampsia with Polycystic Ovary Syndrome as a Risk Factor

“…Normal pregnancy requires programmed cell death at several stages to ensure healthy development, but in PE this process has gone awry [ 40 ]. There is a long track record of Vitamin B5, the precursor of CoA, reducing disease severity by protecting tissues against the effects of apoptosis [ 41 ].…”

MicroRNAs: key regulators of the trophoblast function in pregnancy disorders

“…Autophagy plays a crucial role in placenta formation and embryonic development [ 127 ]. Moderate trophoblast autophagy is important for maintaining a healthy pregnancy, and inappropriate trophoblast autophagy may interfere with cellular homeostasis and lead to placental abnormalities, which can lead to a range of pregnancy disorders [ 128 ]. It was found that in PE, LET-7I inhibits trophoblast autophagy by down-regulating the expression of autophagy-related 4B cysteine peptidase (Atg4B) [ 129 ].…”

The Role of Zinc-Rich Food Consumption on Zinc Level and the Incident of Preeclampsia

“…By dissolving the extracellular matrix, this zinc endopeptidase enzyme functions. 3 Zinc deficiency contributes to a number of birth defects, uterine growth retardation (IUGR), spontaneous abortion, preeclampsia, premature membrane rupture, low birth weight (LBW), labor problems, protracted labor, and postpartum bleeding. The immune system's performance may also be impacted.…”

“…The extracellular matrix is broken down by this zinc endopeptidase enzyme. 3 Zinc deficiency contributes to a number of conditions, including congenital abnormalities, spontaneous miscarriage, intrauterine growth retardation (IUGR), preeclampsia, early rupture of the membranes, low birth weight (LBW), labor problems, protracted labor, and postpartum bleeding. It can also affect immune system function.…”