Physiological and pathological regulation of autophagy in pregnancy

Zhao, Xiaoyan; Jiang, Yuepeng; Jiang, Tianyue; Han, Xinyu; Wang, Ying; Chen, Lu; Xu, Feng

doi:10.1007/s00404-020-05607-1

Cited by 20 publications

(13 citation statements)

References 94 publications

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“…The results of the present study showed a down-regulation in the autophagy proteins in the placenta of pregnant women with PE. Studies of autophagy related to pregnancies complicated by PE are somewhat controversial in the literature ( 2 ) and were first reported by Oh et al ( 23 ) followed by others ( 11 , 24 ). Analyses of proteins involved in the initial stage of autophagy activation showed increased LC3-II expression in the placenta from preeclamptic women compared with control pregnant women, while beclin-1 showed no difference between the groups ( 23 ).…”

Section: Discussionmentioning

confidence: 99%

“…The autophagic process can reduce injuries related to inflammation, infections, neoplasia, and degenerative diseases, and is involved in several pathologies ( 1 ). It is a catabolic lysosomal degradation process that maintains cellular homeostasis and promotes cell survival during stress ( 2 ). This mechanism degrades protein aggregates and damaged organelles in the cytoplasm through the formation of an autophagosome ( 3 ).…”

Section: Introductionmentioning

confidence: 99%

“…During pregnancy, the regulation of autophagy involves three aspects: the embryo, the mother, and the immune crosstalk at the maternal-fetal interface ( 2 ). Some studies reveal that autophagy is present in extravillous trophoblast cells and is important in early pregnancy to promote trophoblastic invasion and uterine vascular remodeling, resulting in normal placentation ( 11 , 12 ).…”

Section: Introductionmentioning

confidence: 99%

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Down-regulation of autophagy proteins is associated with higher mTOR expression in the placenta of pregnant women with preeclampsia

Weel

Ribeiro

Romao‐Veiga

et al. 2022

Braz J Med Biol Res

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Autophagy is a lysosomal degradation pathway that removes protein aggregates and damaged organelles maintaining cellular integrity. It seems to be essential for cell survival during stress, starvation, hypoxia, and consequently to the placenta implantation and development. Preeclampsia (PE) is a multisystemic disorder characterized by the onset of hypertension associated or not with proteinuria and other maternal complications. Considering that the placenta seems to play an important role in the pathogenesis of PE, the objective of the present study was to evaluate protein levels of light chain protein (LC3), beclin-1, and the mammalian target of rapamycin (mTOR) in the placenta of pregnant women with PE. Placental tissues collected from 20 women with PE and 20 normotensive (NT) pregnant women were evaluated for LC3, beclin-1, and mTOR expression by qPCR and immunohistochemistry. The mRNA for LC3 and beclin-1 were significantly lower, while mTOR gene expression was significantly higher in the placenta of pregnant women with PE than in the NT group. Placentas of PE women showed significantly decreased protein expression of LC3-II and beclin-1, whereas mTOR was significantly increased compared with the NT pregnant women. There was a negative correlation between protein expression of mTOR and LC3-II in the placental tissue of PE women. In conclusion, the results showed autophagy deficiency suggesting that failure in this degradation process may contribute to the pathogenesis of PE; however, new studies involving cross-talk between autophagy and inflammatory molecular mechanisms might help to better understand the autophagy process in this obstetric pathology.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Down-regulation of autophagy proteins is associated with higher mTOR expression in the placenta of pregnant women with preeclampsia

Weel

Ribeiro

Romao‐Veiga

et al. 2022

Braz J Med Biol Res

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“…The signaling pathways involved in regulating the biological function of trophoblasts include tyrosine-protein kinase JAK1/STAT, PI3K/AKT, MAPK and TGF-β (42). The results of a previous study demonstrate that activation of the NFκB signaling pathway is also involved in the regulation of trophoblast cell function (43).…”

Section: Discussionmentioning

confidence: 95%

FPR2 serves a role in recurrent spontaneous abortion by regulating trophoblast function via the PI3K/AKT signaling pathway

Zhang

et al. 2021

Mol Med Rep

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Recurrent spontaneous abortion (RSA) effects both the physical and mental health of women of reproductive age. Trophoblast dysfunction may result in RSA due to shallow placental implantation. The mechanisms underlying formyl peptide receptor 2 (FPR2) on the biological functions of trophoblasts remain to be elucidated. The present study aimed to explore the potential functions of FPR2, a G protein-coupled receptor, in placental trophoblasts. The location and expression levels of FPR2 in the villi tissue of patients with RSA were detected using immunohistochemical staining, reverse transcription-quantitative PCR and western blotting. Following the transfection of small interfering RNA targeting FPR2 in HTR-8/SVneo cells, a Cell Counting Kit-8 assay was used to determine the levels of cell viability. Flow cytometry was used to examine the levels of cell apoptosis and gap closure and Transwell assays were carried out to evaluate the levels of cell migration and invasion. A tube formation assay was performed to detect the levels of capillary-like structure formation. Western blotting was used to detect the expression levels of proteins in the associated signaling pathways. The expression of FPR2 was present in villi trophoblasts and was markedly increased in patients with RSA. The levels of trophoblast invasion, migration and tube formation were markedly increased following FPR2 knockdown, whereas the levels of apoptosis were markedly decreased. In addition, FPR2 knockdown caused an increase in the phosphorylation levels of AKT and PI3K. Thus, FPR2 may be involved in the regulation of trophoblast function via the PI3K/AKT signaling pathway. The results of the present study provided a theoretical basis for the use of FPR2 as a target for the treatment of trophoblast-associated diseases, such as RSA.

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“…Many pregnancy-related diseases, such as preeclampsia, ICP, intrauterine growth restriction (IUGR), preterm delivery, and GDM were related to autophagy (Kasture et al, 2021). Furthermore, many biological processes during pregnancy were associated with autophagy, such as fertilization and embryogenesis, implantation, the function of trophoblast, decidualization, maintenance of pregnancy, and immune crosstalk at the maternal-fetal interface (Zhao et al, 2020). As for autophagy in ICP, Shan's understanding was that defects in autophagy were the basis of pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of Quantitative Proteomics With DIA Mass Spectrometry and ceRNA Network in Intrahepatic Cholestasis of Pregnancy

Fang

Zhang

et al. 2022

Front. Cell Dev. Biol.

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Background: Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific complication characterized by pruritus without skin damage and jaundice. The poor perinatal outcomes include fetal distress, preterm birth, and unexpected intrauterine death. However, the mechanism of ICP leading to poor prognosis is still unclear.Methods: We analyzed 10 ICP and 10 normal placental specimens through quantitative proteomics of data-independent acquisition (DIA) to screen and identify differentially expressed proteins. GO, KEGG, COG/KOG, StringDB, InterProScan, Metascape, BioGPS, and NetworkAnalyst databases were used in this study. PITA, miRanda, TargetScan, starBase, and LncBase Predicted v.2 were used for constructing a competing endogenous RNA (ceRNA) network. Cytoscape was used for drawing regulatory networks, and cytoHubba was used for screening core nodes. The ICP rat models were used to validate the pathological mechanism.Results: GO, KEGG, and COG/KOG functional enrichment analysis results showed the differentially expressed proteins participated in autophagy, autophagosome formation, cofactor binding, JAK-STAT signaling pathway, and coenzyme transport and metabolism. DisGeNET analysis showed that these differentially expressed proteins were associated with red blood cell disorder and slow progression. We further analyzed first 12 proteins in the upregulated and downregulated differentially expressed proteins and incorporated clinicopathologic parameters. Our results showed HBG1, SPI1, HBG2, HBE1, FOXK1, KRT72, SLC13A3, MBD2, SP9, GPLD1, MYH7, and BLOC1S1 were associated with ICP development. ceRNA network analysis showed that MBD2, SPI1, FOXK1, and SLC13A3 were regulated by multiple miRNAs and lncRNAs.Conclusion: ICP was associated with autophagy. The ceRNA network of MBD2, SPI1, FOXK1, and SLC13A3 was involved in ICP progression, and these core proteins might be potential target.

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Physiological and pathological regulation of autophagy in pregnancy

Cited by 20 publications

References 94 publications

Down-regulation of autophagy proteins is associated with higher mTOR expression in the placenta of pregnant women with preeclampsia

Down-regulation of autophagy proteins is associated with higher mTOR expression in the placenta of pregnant women with preeclampsia

FPR2 serves a role in recurrent spontaneous abortion by regulating trophoblast function via the PI3K/AKT signaling pathway

Comprehensive Analysis of Quantitative Proteomics With DIA Mass Spectrometry and ceRNA Network in Intrahepatic Cholestasis of Pregnancy

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