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Review
. 2020 May 7;21(9):3298.
doi: 10.3390/ijms21093298.

Disruption of Placental Homeostasis Leads to Preeclampsia

Akitoshi Nakashima  1 , Tomoko Shima  1 , Sayaka Tsuda  1 , Aiko Aoki  1 , Mihoko Kawaguchi  1 , Satoshi Yoneda  1 , Akemi Yamaki-Ushijima  1 , Shi-Bin Cheng  2 , Surendra Sharma  2 , Shigeru Saito  1
Affiliations
Review

Disruption of Placental Homeostasis Leads to Preeclampsia

Akitoshi Nakashima et al. Int J Mol Sci. .

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.

Keywords: autophagy; endoplasmic reticulum stress; inflammation; lysosomes; placenta; preeclampsia; protein aggregation; pyroptosis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
TFEB-mediated autophagy inhibition. Sera from preeclampsia induce hyper-activation of mTOR, which blocks nuclear translocation of TFEB. TFEB inactivation results in the inhibition of autophagy and lysosomal biogenesis in trophoblasts. N: nucleus.
Figure 2
Figure 2
Excessive ER stress-mediated autophagy inhibition. Excessive ER stress, which is enhanced with autophagy inhibition, decreases the number of lysosomes in trophoblasts. The decrease of lysosomes results in the blocking or diminishing of autophagy flux. Meanwhile, ER-phagy might be involved in decreasing ER stress. N: nucleus.
Figure 3
Figure 3
Excessive ER stress-mediated pyroptosis cascade. ER stress activates inflammasomes via Thioredoxin-interacting protein (TXNIP). Activated inflammasome increases the production of active caspase-1, which produces matured form of pro-inflammatory cytokines, IL-18 and IL-1β, and Gasdermin D. Finally, Gasdermin D leads to pyroptosis by forming pores in plasma membranes. Autophagy degrades inflammasome, resulting in preventing inflammation. On the contrary, impaired autophagy may trigger pyroptosis. N: nucleus.
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