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Is there a relationship between early pregnancy loss and maternal serum human X-box binding protein 1 level?
Abstract
The human X-box binding protein 1 is a transcription factor that is expressed by cellular oxidative stress. We aimed to analyze the relationship between early pregnancy loss and maternal blood X-box binding protein 1 levels. Patients who presented to our Obstetrics and Gynecology clinic between October 2019 and February 2020 were included in this study. Patients were divided into two groups: Group 1 included healthy pregnant women and Group 2 included patients who were diagnosed with missed abortion. First, blood samples were taken from the patients in group 2 when they were diagnosed with missed abortion. While evaluating the patients in group 1, the average gestational weeks of the patients in group 1 were calculated and blood samples were taken between the same weeks. Next, patients with healthy pregnancy in group 1 were followed up prospectively and double screening test were performed at the perinatology outpatient clinic at the end of the 1st trimester, and the blood results of the patients with normal results were evaluated. Blood samples extracted from these patients were centrifuged at −80 °C and stored until analyses. Serum X-box binding protein 1 levels were measured using enzyme-linked immunosorbent assay kits (Cusabio, Wuhan, China). Eighty-five patients were included in this study: 42 in Group 1 and 43 in Group 2. There was no difference between the groups in terms of age, body mass index, ethnicity, and systemic illness. Serum X-box binding protein 1 levels were significantly higher in Group 2 (129.89 ± 7.58 ng/L) than in Group 1 (119.56 ± 5.99 ng/L) (p < 0.001). Serum X-box binding protein 1 levels higher than the cut-off value of 119.05 ng/L were associated with a higher risk of early pregnancy loss. Serum X-box binding protein 1 levels may be used to predict early pregnancy loss; however, additional comparative studies are required to confirm this result
... In this study, Uzun et al. showed that serum XBP-1 levels were higher in patients with first-trimester fetal loss compared to healthy pregnant women (129.89 ± 7.58 ng/L; 119.56 ± 5.99 ng/L). They concluded that XBP-1 levels, which indicate increased oxidative stress, may play a role in predicting early pregnancy loss [21]. Similarly, we showed that XBP-1 levels were higher in fetuses with FGR and their mothers. ...
Objective
This study aimed to compare maternal and cord serum X box binding protein 1 (XBP‐1) levels in pregnant women with fetal growth restriction (FGR) with healthy pregnancies.
Materials and Methods
This prospective case‐control study was conducted between January 1, 2022, and May 31, 2022, at the Gynecology and Obstetrics Clinic of Selçuk University Faculty of Medicine Hospital. Forty‐three pregnant women and fetuses with isolated FGR with abdominal circumference (AC) or estimated fetal weight (EFW) below the 10th percentile according to ultrasonographic measurements constituted the study group; 43 healthy pregnant women and fetuses constituted the control group. Serum XBP‐1 levels in prenatal maternal and cord blood were measured by ELISA and compared between the two groups.
Results
The mean maternal blood XBP‐1 level was 1910.22 ± 607.07 ng/L in the FGR group and 1638.89 ± 385.80 ng/L in the control group ( p = 0.044). Cord blood XBP‐1 levels were 1837.72 ± 942.67 and 1346.14 ± 664.09 ng/L in the study and control groups, respectively ( p = 0.006). Maternal XBP‐1 levels were found to discriminate FGR with a sensitivity of 80% and specificity of 60% at a value of 1405 ng/L. For cord blood XBP‐1, 869.2 ng/L was the best cut‐off, with 98% sensitivity and 67% specificity. In ROC analysis, the area under the curve was found to be 0.626 and 0.671, and p values were found to be 0.044 and 0.006 for maternal serum XBP‐1 and cord blood XBP‐1, respectively.
Conclusions
In the study, serum XBP‐1 levels in both maternal and fetal umbilical cord blood were found to be higher in patients with FGR. Considering the role of XBP‐1 in metabolic pathways and cellular functions, XBP‐1 may have an important role in the pathophysiology of FGR.
Background: Spontaneous abortion (SA) is a clinical dilemma during early pregnancy. It has reported that endoplasmic reticulum stress (ERS) was associated with increased incidence of SA. However, the underlying mechanism remains to be elucidated.
Results: ERS related proteins, including GRP78, p-eIF2a, CHOP and XBP1s, were increased in DSCs under endoplasmic reticulum stress (ERS-DSCs). Meanwhile, the inflammatory cytokines and apoptosis were revealed to be enhanced in ERS-DSCs. Interestingly, loss of XBP1 reduced the inflammatory cytokines and apoptosis in ERS-DSCs. Mechanismly, XBP1s coupled with the promoter of a ubiquitin E3 ligase tumour necrosis factor receptor-associated factor 6 (TRAF6). TRAF6 expression was suppressed in ERS-DSCs post treatment with shXBP1, which was accompanied by mitochondrial dysfunction and apoptosis. TRAF6 induced mitochondrial dysfunction in ERS-DSCs by suppressing the mammalian target of rapamycin complex 2 (mTORC2), thereby enhancing ROS levels, mitochondrial dysfunction, and apoptosis. Moreover, Overexpression of mTORC2 abrogated TRAF6-induced ROS, mitochondrial dysfunction, and apoptosis, which involved in the activation of Akt/FoxO1 signaling.
Conclusions: Theses resuluts demonstrated that Loss of XBP1 mediated mitochondrial remodel by regulating TRAF6/mTORC2 signaling pathway plays a critical role in the preservation of DSCs during early pregnancy, which provides novel insights into the pathological mechanism of SA and potential therapeutic targets for SA.
Endoplasmic reticulum stress (ERS) is a protective response to restore protein homeostasis by activating the unfolded protein response (UPR). However, UPR can trigger cell death under severe and/or persistently high ERS. The NLRP3 inflammasome is a complex of multiple proteins that activates the secretion of the proinflammatory cytokine IL-1β in a caspase-1-dependent manner to participate in the regulation of inflammation. The NLRP3 inflammasome involvement in ERS-induced inflammation has not been completely described. The intersection of ERS with multiple inflammatory pathways can initiate and aggravate chronic diseases. Accumulating evidence suggests that ERS-induced activation of NLRP3 inflammasome is the pathological basis of various inflammatory diseases. In this review, we have discussed the networks between ERS and NLRP3 inflammasome, with the view to identifying novel therapeutic targets in inflammatory diseases.
Key points
• Endoplasmic reticulum stress (ERS) is an important factor for the activation of the NLRP3 inflammasomes that results in pathological processes.
• ERS can activate the NLRP3 inflammasome to induce inflammatory responses via oxidative stress, calcium homeostasis, and NF-κB activation.
• The interactions between ERS and NLRP3 inflammasome are associated with inflammation, which represent a potential therapeutic opportunity of inflammatory diseases.
Endoplasmic reticulum (ER) is the cellular compartment where secreted and integral membrane proteins are folded and matured. The accumulation of unfolded or misfolded proteins triggers a stress that is physiologically controlled by an adaptative protective response called Unfolded Protein Response (UPR). UPR is primordial to induce a quality control response and to restore ER homeostasis. When this adaptative response is defective, protein aggregates overwhelm cells and affect, among other mechanisms, synaptic function, signaling transduction and cell survival. Such dysfunction likely contributes to several neurodegenerative diseases that are indeed characterized by exacerbated protein aggregation, protein folding impairment, increased ER stress and UPR activation. This review briefly documents various aspects of the biology of the transcription factor XBP-1 (X-box Binding Protein-1) and summarizes recent findings concerning its putative contribution to the altered UPR response observed in various neurodegenerative disorders including Parkinson's and Alzheimer's diseases.
The lipid composition of cellular organelles is tailored to suit their specialized tasks. A fundamental transition in the lipid landscape divides the secretory pathway in early and late membrane territories, allowing an adaptation from biogenic to barrier functions. Defending the contrasting features of these territories against erosion by vesicular traffic poses a major logistical problem. To this end, cells evolved a network of lipid composition sensors and pipelines along which lipids are moved by non-vesicular mechanisms. We review recent insights into the molecular basis of this regulatory network and consider examples in which malfunction of its components leads to system failure and disease.
X-box binding protein 1 (XBP1) is a central regulator of the endoplasmic reticulum (ER) stress response. It is induced via activation of the IRE1 stress sensor as part of the unfolded protein response (UPR) and has been implicated in several diseases processes. XBP1 can also be activated in direct response to Toll-like receptor (TLR) ligation independently of the UPR but the pathogenic significance of this mode of XBP1 activation is not well understood. Here we show that TLR-dependent XBP1 activation is operative in the synovial fibroblasts (SF) of patients with active rheumatoid arthritis (RA). We investigated the expression of ER stress response genes in patients with active RA and also in patients in remission. The active (spliced) form of (s)XBP1 was significantly overexpressed in the active RA group compared to healthy controls and patients in remission. Paradoxically, expression of nine other ER stress response genes was reduced in active RA compared to patients in remission, suggestive of a UPR-independent process. However, sXBP1 was induced in SF by TLR4 and TLR2 stimulation, resulting in sXBP1-dependent interleukin-6 and tumour necrosis factor (TNF) production.
We also show that TNF itself induces sXBP1 in SF, thus generating a potential feedback loop for sustained SF activation. These data confirm the first link between TLR-dependent XBP1 activation and human inflammatory disease. sXBP1 appears to play a central role in this process by providing a convergence point for two different stimuli to maintain activation of SF.
Alzheimer's disease (AD) is an incurable neurodegenerative disorder clinically characterized by progressive cognitive impairment.
A prominent pathologic hallmark in the AD brain is the abnormal accumulation of the amyloid-β 1–42 peptide (Aβ), but the exact
pathways mediating Aβ neurotoxicity remain enigmatic. Endoplasmic reticulum (ER) stress is induced during AD, and has been
indirectly implicated as a mediator of Aβ neurotoxicity. We report here that Aβ activates the ER stress response factor X-box binding protein 1 (XBP1) in transgenic flies and in mammalian cultured neurons, yielding its active form, the transcription factor XBP1s. XBP1s shows
neuroprotective activity in two different AD models, flies expressing Aβ and mammalian cultured neurons treated with Aβ oligomers.
Trying to identify the mechanisms mediating XBP1s neuroprotection, we found that in PC12 cells treated with Aβ oligomers,
XBP1s prevents the accumulation of free calcium (Ca2+) in the cytosol. This protective activity can be mediated by the downregulation of a specific isoform of the ryanodine Ca2+ channel, RyR3. In support of this observation, a mutation in the only ryanodine receptor (RyR) in flies also suppresses Aβ
neurotoxicity, indicating the conserved mechanisms between the two AD models. These results underscore the functional relevance
of XBP1s in Aβ toxicity, and uncover the potential of XBP1 and RyR as targets for AD therapeutics.
Mutations in superoxide dismutase-1 (SOD1) cause familial amyotrophic lateral sclerosis (fALS). Recent evidence implicates adaptive responses to endoplasmic reticulum (ER) stress in the disease process via a pathway known as the unfolded protein response (UPR). Here, we investigated the contribution to fALS of X-box-binding protein-1 (XBP-1), a key UPR transcription factor that regulates genes involved in protein folding and quality control. Despite expectations that XBP-1 deficiency would enhance the pathogenesis of mutant SOD1, we observed a dramatic decrease in its toxicity due to an enhanced clearance of mutant SOD1 aggregates by macroautophagy, a cellular pathway involved in lysosome-mediated protein degradation. To validate these observations in vivo, we generated mutant SOD1 transgenic mice with specific deletion of XBP-1 in the nervous system. XBP-1-deficient mice were more resistant to developing disease, correlating with increased levels of autophagy in motoneurons and reduced accumulation of mutant SOD1 aggregates in the spinal cord. Post-mortem spinal cord samples from patients with sporadic ALS and fALS displayed a marked activation of both the UPR and autophagy. Our results reveal a new function of XBP-1 in the control of autophagy and indicate critical cross-talk between these two signaling pathways that can provide protection against neurodegeneration.
Considerable progress has been made in identifying the transcription factors involved in the early specification of the B-lymphocyte lineage. However, little is known about factors that control the transition of mature activated B cells to antibody-secreting plasma cells. Here we report that the transcription factor XBP-1 is required for the generation of plasma cells. XBP-1 transcripts were rapidly upregulated in vitro by stimuli that induce plasma-cell differentiation, and were found at high levels in plasma cells from rheumatoid synovium. When introduced into B-lineage cells, XBP-1 initiated plasma-cell differentiation. Mouse lymphoid chimaeras deficient in XBP-1 possessed normal numbers of activated B lymphocytes that proliferated, secreted cytokines and formed normal germinal centres. However, they secreted very little immunoglobulin of any isotype and failed to control infection with the B-cell-dependent polyoma virus, because plasma cells were markedly absent. XBP-1 is the only transcription factor known to be selectively and specifically required for the terminal differentiation of B lymphocytes to plasma cells.
In yeast, the transmembrane protein kinase/endoribonuclease Ire1p activated by endoplasmic reticulum stress cleaves HAC1 mRNA, leading to production of the transcription factor Hac1p that activates the unfolded protein response (UPR). In mammals, no Hac1p counterpart has yet been discovered despite the presence of Ire1p homologs in the endoplasmic reticulum. Instead, the transcription factor ATF6 specific to the mammalian UPR is regulated by intramembrane proteolysis. Here, we identified the transcription factor XBP1, a target of ATF6, as a mammalian substrate of such an unconventional mRNA splicing system and showed that only the spliced form of XBP1 can activate the UPR efficiently. Our results reveal features of the UPR conserved during evolution and clarify the relationship between IRE1- and ATF6-dependent pathways.
Providing adequate nutrition to the fetus is key to a successful pregnancy. The interstitial form of implantation displayed by the human blastocyst is generally associated with early onset of maternal blood flow to the developing placenta, and hence hemotrophic exchange. However, the recent finding that the maternal intraplacental circulation is not fully established until the third month of gestation suggests that human fetal nutrition may be initially histiotrophic. We therefore investigated activity of the uterine glands during early pregnancy. We demonstrate here that these glands remain active until at least wk 10 of pregnancy, and that their secretions are delivered freely into the placental intervillous space. We also demonstrate phagocytic uptake by the placental syncytiotrophoblast of two glycoproteins, the mucin MUC-1 and glycodelin A, synthesized in the maternal glands. Glycodelin was also detected within the epithelium of the secondary yolk sac lining the exocoelomic cavity, indicating that the yolk sac may play an important role in nutrient exchange before vascularisation of the chorionic villi. Our findings demonstrate that the uterine glands are an important source of nutrients during organogenesis, when metabolism is essentially anaerobic.
Laurie Glimcher and colleagues recount their work that showed how the transcription factor XBP1 and the UPR signaling pathway are interconnected during plasma cell differentiation.
Objective: This study aimed to examine the interaction between pregnancy loss and pregnancy intentions on women’s happiness about a subsequent pregnancy.
Background: Anxiety about prior loss persist for women, even during subsequent pregnancies. It is unclear from prior research, whether a prior pregnancy loss shapes attitudes towards and feelings about a subsequent birth.
Methods: Using data from the 2002–2013 National Survey of Family Growth (NSFG), we used logistic regression analyses to explore the implications of a prior pregnancy loss for happiness about a subsequent pregnancy that ends in a live birth. We compared births classified as on-time, mistimed, unwanted, and ambivalent.
Results: Births were more likely to be characterised as on-time if they occurred following a pregnancy loss, and women were less likely to report being happy about a conception if they were ambivalent about the conception and experienced a previous loss. Overall, pregnancy loss alone was not associated with lower levels of happiness about a subsequent birth.
Conclusions: Pregnancy loss can be a highly distressing experience, women’s happiness about a subsequent pregnancy is not reduced due to prior pregnancy loss. Future research should explore why women who were ambivalent about pregnancy reported lower levels of happiness following a loss.
Protein-folding stress at the endoplasmic reticulum (ER) is a salient feature of specialized secretory cells and is also involved in the pathogenesis of many human diseases. ER stress is buffered by the activation of the unfolded protein response (UPR), a homeostatic signalling network that orchestrates the recovery of ER function, and failure to adapt to ER stress results in apoptosis. Progress in the field has provided insight into the regulatory mechanisms and signalling crosstalk of the three branches of the UPR, which are initiated by the stress sensors protein kinase RNA-like ER kinase (PERK), inositol-requiring protein 1α (IRE1α) and activating transcription factor 6 (ATF6). In addition, novel physiological outcomes of the UPR that are not directly related to protein-folding stress, such as innate immunity, metabolism and cell differentiation, have been revealed.
The vast majority of proteins that a cell secretes or displays on its surface first enter the endoplasmic reticulum (ER),
where they fold and assemble. Only properly assembled proteins advance from the ER to the cell surface. To ascertain fidelity
in protein folding, cells regulate the protein-folding capacity in the ER according to need. The ER responds to the burden
of unfolded proteins in its lumen (ER stress) by activating intracellular signal transduction pathways, collectively termed
the unfolded protein response (UPR). Together, at least three mechanistically distinct branches of the UPR regulate the expression
of numerous genes that maintain homeostasis in the ER or induce apoptosis if ER stress remains unmitigated. Recent advances
shed light on mechanistic complexities and on the role of the UPR in numerous diseases.
In a histological study of 184 specimens of complete spontaneous abortion, the following points were delineated. In cases of anomaly or death of the conceptus, there was a reduced trophoblastic penetration into the decidua and into the spiral arteries where physiological changes were limited or absent. Trophoblastic proliferation within the columns and the outer shell was limited with frequent disruption or even disappearance of the shell. These findings seem to be related to the untimely initiation of blood flow in the intervillous space which in turn is associated with arrest of pregnancy and eventual expulsion.
To examine the frequency of chromosomal abnormalities in products of conception from patients with recurrent miscarriages in relation to the number of previous miscarriages.
Retrospective analysis.
Nagoya City University Medical Hospital.
A total of 1,309 women with a history of 2-20 consecutive first-trimester abortions.
Chromosomal analysis performed on products of conception with use of a standard G-banding technique.
The frequencies of abnormal and normal embryonic karyotypes for each number of previous abortions were studied. The subsequent pregnancy outcome of patients whose previous miscarriages were karyotyped were studied along with the predictive value of karyotyping of previous miscarriages for subsequent miscarriages.
The miscarriage rate increased with the number of previous spontaneous abortions. The frequency of abnormal embryonic karyotypes significantly decreased and that of normal embryonic karyotypes significantly increased with the number of previous abortions. Among 71 patients whose embryonic karyotypes were normal, 44 aborted subsequently, and 23 of 60 patients whose embryonic karyotypes were abnormal aborted subsequently. Patients with a previous normal embryonic karyotype aborted more frequently than those with an abnormal karyotype.
The frequency of normal embryonic karyotypes significantly increases with the number of previous abortions, and a normal karyotype in a previous pregnancy is a predictor of subsequent miscarriage.
The aim was to measure changes in the oxygen tension within the human placenta associated with onset of the maternal arterial circulation at the end of the first trimester of pregnancy, and the impact on placental tissues. Using a multiparameter probe we established that the oxygen tension rises steeply from <20 mmHg at 8 weeks of gestation to >50 mmHg at 12 weeks. This rise coincides with morphological changes in the uterine arteries that allow free flow of maternal blood into the placenta, and is associated with increases in the mRNA concentrations and activities of the antioxidant enzymes catalase, glutathione peroxidase, and manganese and copper/zinc superoxide dismutase within placental tissues. Between 8 to 9 weeks there is a sharp peak of expression of the inducible form of heat shock protein 70, formation of nitrotyrosine residues, and derangement of the mitochondrial cristae within the syncytiotrophoblast. We conclude that a burst of oxidative stress occurs in the normal placenta as the maternal circulation is established. We speculate that this may serve a physiological role in stimulating normal placental differentiation, but may also be a factor in the pathogenesis of pre-eclampsia and early pregnancy failure if antioxidant defenses are depleted.
Superoxide (O(2)(-)), hydrogen peroxide (H(2)O(2)), and lipid peroxides are generated in luteal tissue during natural and prostaglandin-induced regression in the rat, and this response is associated with reversible depletion of ascorbic acid. Reactive oxygen species immediately uncouple the luteinizing hormone receptor from adenylate cyclase and inhibit steroidogenesis by interrupting transmitochondrial cholesterol transport. The cellular origin of oxygen radicals in regressing corpora lutea is predominantly from resident and infiltrated leukocytes, notably neutrophils. Reactive oxygen species are also produced within the follicle at ovulation and, like the corpus luteum, leukocytes are the major source of these products. Antioxidants block the resumption of meiosis, whereas the generation of reactive oxygen induces oocyte maturation in the follicle. Although oxygen radicals may serve important physiologic roles within the ovary, the cyclic production of these damaging agents over years may lead to an increased cumulative risk of ovarian pathology that would probably be exacerbated under conditions of reduced antioxidant status.
Free radicals, once the preserve of chemists, are now recognized as playing a central role in many biological systems. They are formed as an inevitable by-product of aerobic respiration and various cytoplasmic processes at a rate dependent upon the prevailing oxygen tension. At physiological concentrations, oxygen and nitrogen free radical species play key roles in intracellular signalling, regulating many homeostatic mechanisms and mediating stress responses. If concentrations exceed cellular defences, however, then indiscriminate damage may occur to lipids, proteins and DNA. Cell function may be perturbed, and in the most severe cases apoptosis may result. Although there are significant species differences, many aspects of early mammalian development, from fertilization through to differentiation of the principal organ systems, take place in vivo in a low oxygen environment. This may serve to protect the embryo from free radical damage, for exposure of early embryos to ambient oxygen concentrations or the products of maternal metabolic disorders is often associated with reduced viability and an increased rate of congenital malformations. Administration of free radical scavengers, including vitamins C and E, can mitigate many of these effects, indicating the importance of a balanced maternal diet to successful reproduction.
In cases of miscarriage, onset of the maternal blood flow to the placenta is precocious and disorganized compared with this event in normal pregnancy. We sought to determine whether this difference is associated with excessive levels of oxidative damage and stress in the placental tissues. Morphological and immunohistochemical markers of cellular stress and damage, including expression of heat shock protein 70, formation of N-Tyr residues, and lipid peroxidation, were increased in tissues obtained from missed miscarriages compared with controls. The effect was greatest in those pregnancies of shorter than 77 days' duration and with evidence of recent fetal demise. It was associated with increased apoptosis and decreased numbers of mitotic cells, indicating that oxidative stress overwhelms cellular antioxidant defense systems. No differences were observed between miscarriages with normal and abnormal karyotypes. The spectrum of villous changes occurring after fetal demise indicates that the duration of placental retention in utero after fetal demise is a critical determinant of villous histology. The causes of many miscarriages remain unclear; however, our findings indicate that placental oxidative stress with resultant damage to the syncytiotrophoblast, secondary to early onset of the maternal circulation, may provide a final common mechanism.
To review the role of oxidative stress in two common placental-related disorders of pregnancy, miscarriage and preeclampsia.
Review of published literature.
Miscarriage and preeclampsia manifest at contrasting stages of pregnancy, yet both have their roots in deficient trophoblast invasion during early gestation. Early after implantation, endovascular trophoblast cells migrate down the lumens of spiral arteries, and are associated with their physiological conversion into flaccid conduits. Initially these cells occlude the arteries, limiting maternal blood flow into the placenta. The embryo therefore develops in a low oxygen environment, protecting differentiating cells from damaging free radicals. Once embryogenesis is complete, the maternal intervillous circulation becomes fully established, and intraplacental oxygen concentration rises threefold. Onset of the circulation is normally a progressive periphery-center phenomenon, and high levels of oxidative stress in the periphery may induce formation of the chorion laeve. If trophoblast invasion is severely impaired, plugging of the spiral arteries is incomplete, and onset of the maternal intervillous circulation is premature and widespread throughout the placenta. Syncytiotrophoblastic oxidative damage is extensive, and likely a major contributory factor to miscarriage. Between these two extremes will be found differing degrees of trophoblast invasion compatible with ongoing pregnancy but resulting in deficient conversion of the spiral arteries and an ischemia-reperfusion-type phenomenon. Placental perfusion will be impaired to a greater or lesser extent, generating commensurate placental oxidative stress that is a major contributory factor to preeclampsia.
Miscarriage, missed miscarriage, and early- and late-onset preeclampsia represent a spectrum of disorders secondary to deficient trophoblast invasion.
An early pregnancy loss (EPL) or first-trimester miscarriage is the most common complication of human reproduction, with an incidence ranging between 50 and 70% of all conceptions. Two-thirds of EPL cases present with a thinner and fragmented trophoblastic shell, and reduced cytotrophoblast invasion of the tips of the spiral arteries. This leads to incomplete plugging during early pregnancy, and premature onset of the maternal circulation throughout the placenta. The excessive entry of maternal blood into the intervillous space has a direct mechanical effect on the villous tissue, and an indirect oxidative stress effect that contributes to cellular dysfunction and/or damage. Correlation of in vivo and in vitro data suggests that overwhelming oxidative stress of the placental tissues represents a common pathophysiological mechanism for the different etiologies of EPL. Autosomal trisomies are the most frequent karyotypic abnormalities found in EPL, but the comparison of data from different cytogenetic studies is difficult because of the lack of clinical information in many cases on maternal age, gestational age, time of fetal demise and the cytogenetic methodology employed. The majority of authors did find a weak association between villous morphologic features and chromosomal abnormalities, with the exception of partial mole triploidy. The comparison of ultrasound findings and placental histological data indicates that villous changes following fetal demise in utero could explain the overall low predictive value of placental histology alone in identifying an aneuploidy or another non-chromosomal etiology. By contrast, the histological features of complete and partial hydatidiform molar EPL are so distinctive that most cases of molar EPL are correctly diagnosed by histological examination alone. Overall, histopathology when correlated with in vivo ultrasound/Doppler has provided novel clues to the pathophysiology of EPL. Prospective studies are needed to evaluate the impact of these findings on routine histopathologic examination in first-trimester miscarriages.
Early pregnancy failure is a common pregnancy complication. This paper reviews the terminology, diagnosis, and treatment of early pregnancy failure. Although surgical curettage has been the standard of care for more than 50 years, additional treatment options exist which appear to be satisfactory to patients. Manual vacuum curettage in the office is an effective alternative to electric vacuum curettage in an operating room. Nonsurgical treatments, including expectant and medical management, are reasonable alternatives depending on the clinical situation and the patient's desires. Clinicians need to understand how these options compare to provide appropriate counseling to patients.
IRE1-mediated unconventional mRNA splicing and S2P-mediated ATF6 cleavage merge to regulate XBP1 in signaling the unfolded protein response
- Lee