Table 1.

Regulation and potential impact of endoplasmic reticulum (ER) stress molecules during normal and abnormal pregnancy conditions according to current literature.

ER Stress Molecules	Alteration/Sources	Action/Significance/Association	Pregnancy Stage/Groups
HSC70	Increased secretion from blastocyst	Paracrine action for proper folding of newly translated and misfolded proteins in decidual cells	Implantation window [133]
GRP78	Increased in endometrial stromal cells	Recurrent miscarriage	Implantation window [114]
IRE1α	Knock-out mouse Smaller placenta and embryo sizes	A reduced VEGF-A levels in the placenta as well as severe dysfunction of the labyrinth placenta	Placentation in mouse [157]
GRP78 and VCP	Down-regulation in decidual cells	Acts with oxidative stress as cofactor for molecular induction of early pregnancy loss	Specimens from Early pregnancy loss [159]
GRP78, P-eIF2α and XBP-1	Increased levels in syncytiotrophoblasts	Increased ER stress during normal labor	Labor vs. Non-labor placentas [154]
GRP78, IRE1 and XBP-1s	-In fetal membranes and myometrium -LPS mediated increase in explant cultures of fetal membranes and myometrium	- Increased ER stress in preterm and term labor - Infection may induce ER stress	Term and spontaneous pre-term labor vs. non-labor placenta specimens. Fetal membranes and myometrium from non-laboring women at the time of term Cesarean section [155]
GRP78, P-eIF2α, ATF4, and CHOP	Increased in placenta	Elevated ER stress and deregulation of proper protein folding during pregnancy	During pregnancy in rat [160]
P-eIF2α	Increased in placenta	Increased ER stress that reduce placental protein synthesis	FGR (GA weeks 28–38) vs. term control (GA weeks 39–40) [161]
GRP78 and 94, P-PERK, eIF2a, P-eIF2a, XBP1, CHOP, IRE1, P-IRE1	Elevated levels in placentas	Exaggerated ER stress in preeclampsia	Preeclamptic (mean GA weeks 33.6) vs. control placentas (mean GA weeks 39.2) [162]
UPR transcription factors ATF4, ATF6α and ATF6β	Increased nuclear localization in the syncytiotrophoblasts	Increased ER stress and contributes to reduced PlGF protein levels	Preeclamptic placentas (GA < 34 weeks ) vs. term control [163]
PERK-induced p-eIF2α, ATF6 and XBP1u	Increased levels in extra-villous trophoblasts, decidual cells and macrophages	Increased ER stress may impair placental growth associated with FGR and FGR + pre-eclampsia	Decidual tissues from FGR (mean GA weeks 31.9) or FGR with pre-eclampsia (mean GA weeks 30.3) vs. term control (mean GA weeks 38.7) [138]
P-IRE1α, ATF6, XBP-1, GRP78 and GRP94	Increased in placental lysates	Impaired ER stress may cause placental dysfunction that triggers preeclampsia	Early-onset (<34 weeks) pre-eclampsia vs. late-onset pre-eclampsia and normotensive controls [164]
P-eIF2α, eIF2α, XBP-1 and GRP78	Increased in placental lysates	Association between increased ER stress and preterm labor	Spontaneous pre-term placentas (due to acute chorioamnionitis and other conditions) vs. term controls [164]