Assessment of placental and maternal stress responses in patients with pregnancy related complications via monitoring of heat shock protein mRNA levels

Abstract

The study describes the stress response in the central cotyledon zone of placental tissue and in maternal whole peripheral blood to pregnancy related complications including gestational hypertension (n = 31), preeclampsia w or w/o fetal growth restriction (n = 95), and fetal growth restriction (n = 39) using real-time RT-PCR and genes encoding Hsp27, Hsp60, Hsp70, Hsp90 and HspBP1 proteins. The placental tissue does not respond to pregnancy induced hypertension, fetal growth restriction and short-term severe preeclampsia that requires immediate termination of gestation. Upregulation of Hsp27, Hsp90 and HspBP1 appears just in case of long-term deteriorated conditions (usually in mild preeclampsia, that enable further continuation of gestation, when properly treated). On the other hand, maternal circulation is able to reflect both maternal and fetal pathologic conditions. While pregnancy related complications always induce upregulation of Hsp70 and downregulation of Hsp90 in maternal whole peripheral blood, the increase of Hsp60 mRNA levels occurs entirely in patients with preeclampsia and/or fetal growth restriction. Hsp60, Hsp70 and Hsp90 are dysregulated in maternal circulation irrespective of the severity of the disease (in both mild and severe preeclampsia) and the requirements for the delivery (before and after 34th week of gestation). Nevertheless, the highest Hsp60 mRNA levels may be observed in pregnancies with signs of the centralization of the fetal circulation associated with fetal hypoxia.

Consensus strategy in genes prioritization and combined bioinformatics analysis for preeclampsia pathogenesis

“…As we previously explained, this can also be accomplished through PI3K and the involvement of AKT1. The expression of HSP90 could be polemic because apparently it is related with the disease progression and also placenta location [68]. However several authors had being found an increment in the placenta expression of HSP90 in PE [68–70] at mRNA and protein levels.…”

Expression Profile of C19MC microRNAs in Placental Tissue in Pregnancy-Related Complications

“…In severe early-onset FGR, there is increased expression of genes regulating intrinsic apoptosis in both the placenta and maternal blood (Whitehead et al, 2013). AHSA2 AHA1, activator of heat shock 90 kDa protein ATPase homolog 2 The upregulation of Hsp90, found in placental tissues affected with mild preeclampsia (Hromadnikova et al, 2015), may be associated with downregulation of miR-520a* and miR-525. Both microRNAs have been predicted to regulate the expression of the AHSA2 gene, which is an activator of Hsp90 protein ATPase homolog 2.…”

“…Heat shock transcription factory family member 5 The upregulation of Hsp27, Hsp90, and HspBP1, found in placental tissues affected with mild preeclampsia (Hromadnikova et al, 2015), may be associated with downregulation of miR-520a* and miR-525. Both microRNAs have been predicted to regulate the expression of HSF5 gene, a transcriptional activator of heat shock genes.…”

“…Heat shock protein 90 kDa alpha (cytosolic), class A member 1 (Hsp90) The upregulation of Hsp90, found in placental tissues affected with mild preeclampsia (Hromadnikova et al, 2015), may be associated with downregulation of miR-526a, which has been predicted to regulate expression of the HSP90AA1 gene encoding heat shock protein 90 (Hsp90), a molecular chaperon essential for activating many signaling proteins in the eukaryotic cells.…”

Interaction between the inducible 70-kDa heat shock protein and autophagy: effects on fertility and pregnancy

“…Hsp70 concentrations are also elevated in placental tissues from women with preeclampsia, especially in those with early onset disease (Yung et al 2014). More recently, hsp70 mRNA levels in whole blood were found to be significantly elevated in gestational hypertension, preeclampsia, and IUGR (Hromadnikova et al 2015). Variations in the expression of autophagic markers (Gao et al 2015) and hsp70 levels (Johnstone et al 2011) in preeclamptic placentae at different gestational ages may be an example of the pathological dysregulation of these two processes that contribute to the development of preeclampsia.…”