Preeclampsia, a serious and potentially life-threatening medical complication occurring during pregnancy, is characterized by hypertension and often accompanied by proteinuria and multiorgan dysfunction. It is classified into two subtypes based on the timing of diagnosis: early-onset (EO-PE) and late-onset preeclampsia (LO-PE). Despite being less severe and exhibiting distinct pathophysiological characteristics, LO-PE is more prevalent than EO-PE, although both conditions have a significant impact on placental health. Previous research indicates that different pathophysiological events within the placenta may contribute to the development of preeclampsia across multiple pathways. In our experimental study, we investigated markers of oxidative stress, ferroptosis, and lipid peroxidation pathways in placental tissue samples obtained from women with LO-PE (n = 68) compared to healthy control pregnant women (HC, n = 43). Through a comprehensive analysis, we observed an upregulation of specific molecules associated with these pathways, including NADPH oxidase 1 (NOX-1), NADPH oxidase 2 (NOX-2), transferrin receptor protein 1 (TFRC), arachidonate 5-lipoxygenase (ALOX-5), acyl-CoA synthetase long-chain family member 4 (ACSL-4), glutathione peroxidase 4 (GPX4) and malondialdehyde (MDA) in women with LO-PE. Furthermore, increased ferric tissue deposition (Fe³⁺) was observed in placenta samples stained with Perls’ Prussian blue. The assessment involved gene and protein expression analyses conducted through RT-qPCR experiments and immunohistochemistry assays. Our findings underscore the heightened activation of inflammatory pathways in LO-PE compared to HC, highlighting the pathological mechanisms underlying this pregnancy disorder.

Pre-eclampsia is a harmful and potentially lethal medical condition during pregnancy clinically diagnosed by hypertension and commonly accompanied by proteinuria and multiorgan affections. According to the time of diagnosis, it is differentiated between early-onset (EO-PE) and late-onset preeclampsia (LO-PE). Despite being less dangerous and presenting distinct pathophysiological signatures, LO-PE has a greater prevalence than EO-PE, both having significant consequences on the placenta. Previous works have evidenced that exacerbated inflammation in this organ might play a potential pathogenic role in the development of pre-eclampsia, and there is some preliminary evidence that the hyperactivation of inflammasomes can be related to the altered immunoinflammatory responses observed in the placentas of these patients. However, the precise role of inflammasomes in the placentas of women with LO-PE remains to be fully understood. In this work, we have studied the gene and protein expression of the main components related to the canonical and non-canonical pathways of the inflammasome NLRP3 (NLRP3, ASC, caspase 1, caspase 5, caspase 8, interleukin 1β, and interleukin 18) in the placental tissue of women with LO-PE. Our results show a marked increase in all these components in the placentas of women who have undergone LO-PE, suggesting that NLRP3 inflammasome plays a potentially pathophysiological role in the development of this entity. Future works should aim to evaluate possible translational approaches to this dysregulation in these patients.

Preeclampsia (PE) is a complex multisystem disease characterized by hypertension of sudden onset (>20 weeks’ gestation) coupled with the presence of at least one additional complication, such as proteinuria, maternal organ dysfunction, or uteroplacental dysfunction. Hypertensive states during pregnancy carry life-threatening risks for both mother and baby. The pathogenesis of PE develops due to a dysfunctional placenta with aberrant architecture that releases factors contributing to endothelial dysfunction, an antiangiogenic state, increased oxidative stress, and maternal inflammatory responses. Previous studies have shown a correlation between grade 3 placental calcifications and an elevated risk of developing PE at term. However, little is known about the molecular pathways leading to placental calcification. In this work, we studied the gene and protein expression of c-Jun N-terminal kinase (JNK), Runt-related transcription factor 2 (RUNX2), osteocalcin (OSC), osteopontin (OSP), pigment epithelium-derived factor (PEDF), MSX-2/HOX8, SOX-9, WNT-1, and β-catenin in placental tissue from women with late-onset PE (LO-PE). In addition, we employed von Kossa staining to detect mineral deposits in placental tissues. Our results show a significant increase of all these components in placentas from women with LO-PE. Therefore, our study suggests that LO-PE may be associated with the activation of molecular pathways of placental calcification. These results could be the starting point for future research to describe the molecular mechanisms that promote placental calcification in PE and the development of therapeutic strategies directed against it.

Preeclampsia is one of the most worrisome complications during pregnancy, affecting approximately 1 out of 20 women worldwide. Preeclampsia is mainly characterized by a sustained hypertension, proteinuria, also involving a significant organ dysfunction. Moreover, 25% of the cases could be classified as severe preeclampsia (SP), a serious condition that could be life-threatening for both the mother and fetus. Although there are many studies focusing on preeclampsia, less efforts have been made in SP, frequently limited to some specific situations. Thus, the present study aims to conduct a comparative analysis of risk factors, maternal characteristics, obstetric and neonatal outcomes and maternal complications in patients with severe preeclampsia versus patients without severe preeclampsia. Hence, 235 cases and 470 controls were evaluated and followed in our study. We described a set of variables related to the development of severe preeclampsia, including maternal age > 35 years (69.8%), gestational (26.8%) or chronic arterial hypertension (18.3%), obesity (22.6%), use of assisted reproduction techniques (12.3%), prior history of preeclampsia (10.2%) and chronic kidney disease (7.7%) All patients had severe hypertension (>160 mmHg) and some of them presented with additional complications, such as acute renal failure (51 cases), HELLP syndrome (22 cases), eclampsia (9 cases) and acute cerebrovascular accidents (3 cases). No case of maternal death was recorded, although the SP group had a higher cesarean section rate than the control group (60% vs. 20.9%) (p < 0.001), and there was a notably higher perinatal morbidity and mortality in these patients, who had a prematurity rate of 58.3% (p < 0.001) and 14 perinatal deaths, compared to 1 in the control group. Overall, our study recognized a series of factors related to the development of SP and related complications, which may be of great aid for improving the clinical management of this condition.

Preeclampsia (PE) is a serious hypertensive disorder affecting 4–5% of pregnancies globally, leading to maternal and perinatal morbidity and mortality and reducing life expectancy in surviving women post-gestation. Late-onset PE (LO-PE) is a clinical type of PE diagnosed after 34 weeks of gestation, being less severe than the early-onset PE (EO-PE) variant, although both entities have a notable impact on the placenta. Despite the fact that most studies have focused on EO-PE, LO-PE does not deserve less attention since its prevalence is much higher and little is known about the role of the placenta in this pathology. Via RT-qPCR and immunohistochemistry methods, we measured the gene and protein expressions of several macroautophagy markers in the chorionic villi of placentas from women who underwent LO-PE (n = 68) and compared them to normal pregnancies (n = 43). We observed a markedly distinct expression pattern, noticing a significant drop in NUP62 expression and a considerable rise in the gene and protein expressions of ULK1, ATG9A, LC3, ATG5, STX-17, and LAMP-1 in the placentas of women with LO-PE. A major induction of autophagic processes was found in the placental tissue of patients with LO-PE. Abnormal signaling expression of these molecular patterns in this condition aids in the understanding of the complexity of pathophysiology and proposes biomarkers for the clinical management of these patients.

Introduction: At present, we are witnessing an increase in preeclampsia, especially the most severe forms, which are associated with an increased risk of maternal-perinatal morbidity and mortality. As a severity criterion, acute kidney injury (AKI) has been associated with a worse prognosis, and for this reason, the maternal and perinatal variables associated with AKI in patients with severe preeclampsia (SP) were analysed in this study. Methods: An observational, retrospective, single-centre study of patients with SP treated at a tertiary hospital between January 2007 and December 2018 was conducted. The case criteria based on the criteria established by the ACOG Practice Guidelines for Gestational Hypertension and Preeclampsia. AKI is considered when serum creatinine exceeds 1.1 mg/dL in a pregnant woman with previously normal renal function. In patients with existing chronic kidney disease (CKD), it is referred to as AKI if the baseline serum creatinine increases by 1.5 fold. Pregestational, gestational and postpartum variables were analysed up to 12 weeks postpartum using univariate and multivariate logistic regression analysis. Results: During the study period, 76,828 births were attended, and 303 pregnant women were diagnosed with SP. The annual incidence of SP increased gradually throughout the study period, reaching 1.79/100 births/year in 2018. Acute kidney injury (AKI) occurred in 24.8% of the patients. The multivariate analysis revealed an increased association with a history of previous CKD, the use of assisted reproductive techniques and caesarean section. Uric acid and thrombotic microangiopathy (TMA) had a high correlation with AKI. Indications for caesarean section are associated with AKI in SP. Regarding perinatal outcomes in cases of AKI, there was a higher percentage of neonates who required foetal lung maturation with steroids and an increased need for NICU admission. No case of maternal death was recorded; however, an increase in neonatal mortality was found among patients who did not develop AKI. After 12 weeks postpartum, 72 patients were referred to the nephrology consultation for persistent hypertension, proteinuria or renal failure. Conclusions: In preeclampsia, AKI is a common complication, especially among patients with a history of CKD, those who became pregnant using assisted reproduction techniques and those who delivered via caesarean section. The perinatal impact of AKI is mainly centred on a higher rate of NICU admission and a lower mortality rate. Among biochemical and haematological markers, the uric acid level prior to renal failure has a direct and significant correlation with the risk of AKI, as does the development of TMA in patients with preeclampsia. Therefore, the monitoring of renal function in cases of preeclampsia should be strict, and referral for a nephrology consultation may be necessary in some cases.