Disruption of Placental Homeostasis Leads to Preeclampsia

Abstract

Placental homeostasis is directly linked to fetal well-being and normal fetal growth. Placentas are sensitive to various environmental stressors, including hypoxia, endoplasmic reticulum stress, and oxidative stress. Once placental homeostasis is disrupted, the placenta may rebel against the mother and fetus. Autophagy is an evolutionally conservative mechanism for the maintenance of cellular and organic homeostasis. Evidence suggests that autophagy plays a crucial role throughout pregnancy, including fertilization, placentation, and delivery in human and mouse models. This study reviews the available literature discussing the role of autophagy in preeclampsia.

Placental autophagy failure: A risk factor for preeclampsia

“…Lysosomal‐associated membrane protein 1 and beta‐galactosidase (a hydrolase in lysosomes), which are associated with the reduction of lysosomes by ER stress in trophoblasts, and which are secreted into the cultured medium, also show a significant decrease in the sera of women suffering from preeclampsia, when compared with those of normal pregnant women 54 . A decrease in serum beta‐galactosidase levels is also observed in the sera of normotensive women with fetal growth restriction, suggesting that it could be used as a marker for detecting ER stress associated with autophagy impairment in placental growth restriction 55 …”

“…54 A decrease in serum beta-galactosidase levels is also observed in the sera of normotensive women with fetal growth restriction, suggesting that it could be used as a marker for detecting ER stress associated with autophagy impairment in placental growth restriction. 55…”

Curcumin: Could This Compound Be Useful in Pregnancy and Pregnancy-Related Complications?

“…Preeclampsia (PE) is a systemic syndrome characterized by hypertension and proteinuria, which begins after 20 weeks of gestation; it occurs in 2–8% of pregnancies, and it is a leading cause of maternal and fetal morbidity and mortality [ 72 ]. Although the pathophysiology of PE remains to be elucidated, alterations in maternal vascular physiology have been described, leading to a generalized vasoconstrictive state, systemic oxidative stress, inflammation, and endothelial cell dysfunction, with severe adverse effects on the placenta, one of the major organs that develops after conception [ 73 , 74 ]. Strategies to reverse or arrest the pathological processes of PE are aimed at reducing excessive inflammatory response, micro-emboli formation, and vasoconstriction by using specific drugs or natural products [ 75 ].…”

Aggrephagy Deficiency in the Placenta: A New Pathogenesis of Preeclampsia

“…Furthermore, this phenomenon was observed in Atg7 cKO placentas. Thus, aggrephagy deficiency, including macroautophagy deficiency, contributes to the deposition of protein aggregates in preeclamptic placentas [ 5 ]. In terms of the underlying molecular mechanism, downregulation of transcriptional factor EB (TFEB) is responsible for lysosomal dysfunction-mediated autophagy deficiency [ 28 ].…”

“…As the placental size is closely related to fetal size, failure of placental development results in fetal growth restriction (FGR) and various disorders in the offspring. Multiple factors, including hypoxia, systemic inflammation, failure of tolerance against the fetal antigen, failure of autophagy, or an increase in antiangiogenic factors, have been identified as possible causes of preeclampsia [ 5 ]. Among them, the increase in antiangiogenic factors, soluble Fms-like tyrosine kinase-1 (sFlt1) and soluble endoglin, in the maternal circulation are the most frequently investigated both in preeclampsia clinically and in basic science.…”