Endoplasmic reticulum stress induced by oxidative stress in decidual cells: a possible mechanism of early pregnancy loss

Abstract

Early pregnancy loss (EPL) is one of the most common complications of human reproduction. Combined with our previous proteomic studies on villous and decidual tissues of EPL, we found that alterations of the proteins involved in oxidative stress (OS), unfolded protein response (UPR) and proteolysis presented a complex and dynamic interaction at the maternal-fetal interface. In the present study, we developed a cell model of OS using normal decidual cells to examine cell viability and expression levels of proteins related to endoplasmic reticulum stress (ER stress) and UPR. We found that glucose regulated protein 78 (GRP 78) and ubiquitinated proteins were significantly up-regulated in hydrogen peroxide (H(2)O(2)) treated decidual cells in a dose-dependent manner. Excessive OS could influence proper function of UPR by decreasing VCP in decidual cells, thereby leading to cell damage as well as inhibition of cell growth and activation of apoptosis. Furthermore, when pretreated with MG 132, a pharmacological inhibition of the proteasome, the H(2)O(2) treated decidual cells became less viable and could not up-regulate the expression level of GRP 78 to resolve the protein-folding defects, which indicating that malfunction of UPR in decidual cells might aggravate the inhibitory effect of OS in decidual cells. The present results reveal that abnormal protein profiles associated with OS induced ER stress and malfunction of UPR might be involved in the development of EPL, and OS and ER stress are potential targets for pregnant care and prognosis in normal pregnancy and its disorders.

Induction of Apoptosis by Hypertension Via Endoplasmic Reticulum Stress

“…This finding suggests that hypertension actives ER stress in the rat heart. Increased GRP78 has been reported in ER stress-associated apoptosis in decidual cells [16] and in renal proximal tubular cells [17], in synchronous multiple primary cancers in the oesophagus and stomach [18], in diabetic cardiomyopathy [19], and in mineralising tissues and mesenchymal cells [20]. …”

“…CHOP is a transcription factor that is expressed at low levels under homeostatic conditions and strongly induced by a variety of signals that lead to ER stress [28]. Caspase-12 is located on the ER membrane and is activated only by ER stress [3,16,21]. CHOP and Caspase-12 are induced at the transcriptional and translational levels when the ER is stressed.…”

Regulatory T cells, inflammation, and endoplasmic reticulum stress in women with defective endometrial receptivity

“…Thus, deregulated HSPA5 expression might play a role in defective implantation. Very recently it has been reported that ER stress mediated by oxidative stress might be involved in early pregnancy loss (44). ER stress is particularly relevant to secretory cells and has been recently linked, in addition to oxidative stress, to inflammation (18).…”

Diffuse decidual leucocytoclastic necrosis and NK cell aggregates: two distinct features of miscarriage

“…Shallow placentation, oxidative stress and endoplasmic reticulum stress of placental and decidual tissues have been implicated as primary features of pre-eclampsia and fetal growth restriction 28–32. Previous studies have proposed that unexplained miscarriage has a molecular signature of oxidative stress of the placenta,33 34 and early pregnancy loss is associated with oxidative stress/endoplasmic reticulum stress of the decidua 35. The potential relationship between DDLN and these biological signatures needs further study.…”