Pregnancy-related Disorders Research Articles

A Review of Gestational Trophoblastic Disease in A Tertiary Hospital in NothWestern Nigeria

Background: Gestational trophoblastic disease (GTD) encompasses a range of pregnancy related disorders of complete and partial hydatidiform mole, and the malignant disorders of invasive mole, choriorcarcinoma and the rare placental-site trophoblastic tumour. Aims: The study is aimed to determine; (1) the prevalence of gestational trophoblastic tumours in Federal Medical Centre, Birnin Kebbi (2) The pattern of presentation and (3) the maternal outcome in patients with GTD managed at the Deparrtment of Obstetrics and Gynaecilogy of Federal Medical Centre, Birnin Kebbi, Nigeria. Methodology: This was a retrospective study of the cases of gestational trophoblastic disease managed at the Departmenrt of Obstetrics and Gynaecology of Federal Medical Centre, Birnin Kebbi, Noth-Western, Nigeria between the 1st January, 2010 and 31st of December, 2019. Results: There were 82 cases of gestational trophoblastic diseases out of 5,088 gynaecological admissions during the study period, thereby constituting 1.6% of the total gynaecological admissions. There were 16,572 deliveries; hence the incidence of GTD was 4.9 per 1000 deliveries. The age range of the patients is between 15–45years, with a mean age of 26.84 years. Of the 82-case managed during the period under review, only 74 (90.2%) of patients’ case notes were retrieved for analysis. Hydatidiform mole was the commonest among them, accounted for 56.8% of cases and 6.9% of the cases were choriocarcinoma. In 50% of cases there was no documented histological diagnosis. GTD was commoner at the extremes of reproductive age. Conclusion: The incidence of GTD in this study was 4.9 per 1000 deliveries. Vaginal bleeding was the commonest presenting symptom. Early diagnosis and appropriate treatment of this disease is a good determinant of the disease outcomes, while late presentation was associated with high maternal mortality as found in this study.

Down-Regulation of PLAC1 in the Placenta of Gestational Diabetes Mellitus Patients and its Clinical Significance

Background: Placenta-specific 1 (PLAC1) is specifically expressed in the placenta and plays a fundamental role in placenta function. Aberrant expression of PLAC1 has been reported in pregnancy-related disorders; however, its expression in gestational diabetes mellitus (GDM) has not been clearly elucidated. This study aimed to investigate the expression of PLAC1 in the placenta of GDM patients, and its relationship with clinical characteristics. Methods: This was a case-control study. Placental tissues were collected from 37 GDM patients (GDM group) and 38 pregnant women with normal glucose tolerance (control group), matched with respect to maternal age and gestational weeks. We examined the expression of PLAC1 in the placenta of both groups and determined its association with clinical indicators. The localization of PLAC1 was confirmed by immunohistochemistry analyses. Results: PLAC1 expression was significantly lower in the placenta of GDM patients. For the control group, PLAC1 was positively correlated with pre-pregnancy body mass index (BMI), BMI at delivery, the fasting insulin, triglyceride levels, and homeostasis model assessment during delivery. In the case of GDM patients, there was no correlation between PLAC1 and these indices. Additionally, PLAC1 protein was mainly expressed in the cytoplasm of syncytiotrophoblasts and chorionic stromal cells. Conclusions: The expression of PLAC1 was reduced in the GDM placenta, which provides insight into the pathophysiological changes occurring in the placenta of these patients.

Factors Associated with the Severity of Pregnancy-Related Hypertensive Disorder: Significance of Clinical, Laboratory, and Histopathological Features.

The purpose of this paper is to evaluate the association of maternal clinical and laboratory features and placental histopathological changes with disease severity in pregnancy-related hypertensive disorders. From January 2021 to December 2021, clinical and laboratory data at the time of delivery and histopathological features of the placenta were collected from pregnant women with pregnancy-related hypertensive disorders at a single institution. The women were classified according to the pregnancy-related hypertensive disorder clinical severity, and each variable was compared accordingly. Gestational age-matched normotensive groups were also compared. Univariate and multivariate regression analyses were used to identify factors influencing pregnancy-related hypertensive disorder severity. Fifty-eight pregnancies were analyzed. Maternal albumin levels before delivery (beta coefficient −0.83, p = 0.043) and increased placental syncytial knots (beta coefficient 0.71, p = 0.026) are important parameters that are closely related to disease severity in women with pregnancy-related hypertensive disorders. The combination of albumin, PAPP-A, total bilirubin, and eGFR levels appears to be optimal for predicting pregnancy-related hypertensive disorder severity.

A Comparative Study of Local Dietary Intake Among Subjects with Hypertensive Disorders of Pregnancy Attending Antenatal Care

Background: Hypertensive disorders of pregnancy remain among the most significant causes of pregnancy-related complications. The research by the Dietary Approaches to Stop Hypertension (DASH) group revealed that non-pharmacological measures and intervention such as diet can be used to control blood pressure. Objective: This study was completed to determine the frequency of consumption of local food among females who were pregnant and their relationship with pregnancy-related hypertensive disorders. Methods: This was a descriptive research study of females who were pregnant with pre-eclampsia (PE) and gestational hypertension (GH) who presented at the Federal Medical Centre (FMC), Abeokuta, Nigeria. During the study period (September–October 2019) at the tertiary healthcare centre, 45 subjects who were pregnant were select from a PE and GH group, and matched with 45 patients with normotension. Comparison of bean meal onsumption (gbegiri) and bone meal (gbure-oloboro) consumption in subjects who were pregnant did not reveal statistically significant differences in those with PE and GH. Results: The findings reveal a statistically significant difference in milk consumption between females who were pregnant with mild and severe PE (p=0.019). There was also a statistically significant difference in subjects with mild and severe GH who consumed milk (p=0.003).

Sickle Cell Trait and Adverse Pregnancy Outcomes: Is There a Link?

ObjectiveThe objective is to assess the overall prevalence of maternal and neonatal pregnancy-related complications, and to compare their frequency among women with sickle cell trait (SCT) and those with normal hemoglobin patterns to examine the association between SCT and maternal and neonatal outcomes.MethodsA retrospective cross-sectional case-control study was conducted by reviewing medical data from the labor room registry book and electronic database. All pregnant ladies delivered in Salmaneya medical complex from January 1 to December 31, 2019 were included. Patients were divided into two groups based on the presence or absence of SCT. Adverse maternal and neonatal outcomes were compared between the two groups. ResultsOut of the 5,067 pregnant women reviewed, 934 (18.4%) were included (460 (49.3%) with SCT and 474 (50.7%) with healthy controls). Overall, maternal, and neonatal complications were noted in 40.8% (n=381) and 16.3% (n=152), respectively. In univariate analysis, patients with SCT were significantly more likely to underwent cesarean sections compared to healthy women, 28.7% (n=132) vs. 21.7% (n=103), respectively (P=0.044) and to have more intrauterine fetal death (3% [n=14] vs. 0.2% [n=1], respectively (P<0.0001). No significant differences were found between the two groups in terms of the occurrence of the pregnancy-related hypertensive disorder, gestational diabetes, small for gestational age, and preterm delivery. ConclusionThe result of this large, retrospective cross-sectional, case-control study shows that pregnant women with SCT were associated with an increase in intrauterine fetal death in comparison with pregnant women with normal hemoglobin. There were no differences found in pregnancy-related hypertensive disorder, gestational diabetes, small for gestational age, and preterm delivery. This result will emphasize the requirement of additional studies to scrutinize these findings and to determine whether there may be a benefit of a unique antenatal surveillance guideline for such patients.

Interleukin-33 regulates the endoplasmic reticulum stress of human myometrium via an influx of calcium during initiation of labor.

Inflammation is currently recognized as one of the major causes of premature delivery. As a member of the interleukin-1β (IL-1β) family, interleukin-33 (IL-33) has been shown to be involved in normal pregnancy as well as a variety of pregnancy-related disorder. This study aims to investigate the potential function of IL-33 in uterine smooth muscle cells during labor. Myometrium samples from term pregnant (≥37 weeks gestation) women were either frozen or cells were isolated and cultured. Immunohistochemistry and western blotting were used to assess the distribution of IL-33. Cultured cells were incubated with lipopolysaccharide (LPS) to mimic inflammation as well as in the presence of 4μ8C (IRE1 inhibitor III) to block endoplasmic reticulum (ER) stress and BAPTA-AM, a calcium chelator. LPS reduced the expression of nuclear IL-33 in a time-limited manner and induced ER stress. However, knockdown of IL-33 increased LPS-induced calcium concentration, ER stress and phosphorylation of nuclear factor kappa-B (NF-κB), and P38 mitogen-activated protein kinase (P38 MAPK). In addition, siRNA IL-33 further stimulates LPS enhanced cyclooxygenase-2 (COX-2) expression via NF-κB and p38 pathways. IL-33 expression was decreased in the nucleus with the onset of labor. LPS-induced ER stress and increased expression of the labor-associated gene, COX-2, as well as IL-6 and IL-8 in cultured myometrial cells. IL-33 also increased COX-2 expression, but after it was knocked down, the stimulating effect of LPS on calcium was enhanced. 4μ8C also inhibited the expression of COX-2 markedly. The expression of calcium channels on the membrane and intracellular free calcium ion were both increased which was accompanied by phosphorylated NF-κB and p38. These data suggest that IL-33 may be involved in the initiation of labor by leading to stress of the ER via an influx of calcium ions in human uterine smooth muscle cells. This study was supported by grants from the National Natural Science Foundation of China (No. 81300507).

Nanotechnologies in Obstetrics and Cancer during Pregnancy: A Narrative Review.

Nanotechnology, the art of engineering structures on a molecular level, offers the opportunity to implement new strategies for the diagnosis and management of pregnancy-related disorders. This review aims to summarize the current state of nanotechnology in obstetrics and cancer in pregnancy, focusing on existing and potential applications, and provides insights on safety and future directions. A systematic and comprehensive literature assessment was performed, querying the following databases: PubMed/Medline, Scopus, and Endbase. The databases were searched from their inception to 22 March 2022. Five independent reviewers screened the items and extracted those which were more pertinent within the scope of this review. Although nanotechnology has been on the bench for many years, most of the studies in obstetrics are preclinical. Ongoing research spans from the development of diagnostic tools, including optimized strategies to selectively confine contrast agents in the maternal bloodstream and approaches to improve diagnostics tests to be used in obstetrics, to the synthesis of innovative delivery nanosystems for therapeutic interventions. Using nanotechnology to achieve spatial and temporal control over the delivery of therapeutic agents (e.g., commonly used drugs, more recently defined formulations, or gene therapy-based approaches) offers significant advantages, including the possibility to target specific cells/tissues of interest (e.g., the maternal bloodstream, uterus wall, or fetal compartment). This characteristic of nanotechnology-driven therapy reduces side effects and the amount of therapeutic agent used. However, nanotoxicology appears to be a significant obstacle to adopting these technologies in clinical therapeutic praxis. Further research is needed in order to improve these techniques, as they have tremendous potential to improve the accuracy of the tests applied in clinical praxis. This review showed the increasing interest in nanotechnology applications in obstetrics disorders and pregnancy-related pathologies to improve the diagnostic algorithms, monitor pregnancy-related diseases, and implement new treatment strategies.

Plasma drop and thin-film revealed distinguished molecular structure in pre-eclampsia: An investigation using synchrotron Fourier-transform infrared microspectroscopy

Pre-eclampsia (PE) is a serious pregnancy-related disorder and the leading cause of maternal and fetal mortality and morbidity worldwide. The etiology of PE is poorly understood and a definitive diagnosis is still lacking. Herein, we used synchrotron-FTIR microspectroscopy as a new analytical tool to investigate the molecular changes in the structure and intensity of lipids (spectral range 3050–2800 cm−1) and protein-carbonyl (spectral range 1855–1485 cm−1) components of the plasma and link them to the pathogenesis of the disease. In the lipid region, an increase in the CH2 and CH3 peaks intensity was noticed in PE group compared to normotensive pregnancy reflecting abnormalities in the lipid profile and a high level of LDL. Increased CH2/CH3 ratio and red shifts were observed in the lipid region in PE highlighting structural variations of lipids and transformation of conformation of lipid tails. In the protein-carbonyl region, a decrease in the amide I and II absorption signals in the plasma of PE compared to normotensive controls was evident, and a red shift was noticed in the amide I region reflecting conformational changes and rearrangement in the α-helix secondary structure of the protein. Moreover, malondialdehyde level and lipid carbonyl peak at 1743 cm−1 were higher and more intense in PE due to the oxidative stress condition in PE. Spectral analysis of plasma drop from PE revealed that lipid and protein components tend to concentrate more in the central region of the drop, and that the most intense wavenumber values for the lipid and amide I region in the plasma drop were very comparable to their analogous in plasma film. Taken together, the current work provides evidence of the promising role of synchrotron-FTIR microspectroscopy in providing a better understanding of the pathophysiology of PE.

A new look at the role of nitric oxide in preeclampsia: Protein S-nitrosylation.

The formation of S-nitrosothiols (SNOs) occurs with the reaction of nitric oxide (NO) and free thiol groups in proteins. This process, called S-nitrosylation, allows NO to interfere with or even modulate a variety of cellular functions, culminating with the modification of protein trafficking, redox state, and cell cycle. Furthermore, NO plays a role in modulating a wide range of functions in endothelial cells specifically, including inflammation, apoptosis, permeability, migration, and cell growth. As such, NO acts as a mediator in several physiological processes. The interaction between endothelial nitric oxide synthase (eNOS) and proteins that are to be targeted for S-nitrosylation is a key determinant of the specificity of NO signaling. Deficits in the bioavailability of NO have been associated with pregnancy-related disorders, such as preeclampsia (PE). The study of S-nitrosylation in PE, as well as the identification of targeted proteins, may contribute to a better understanding of its pathophysiology and the development of drugs for the treatment of PE patients. In this review, we aimed to present the mechanism of S-nitrosylation, the regulatory pathways, and some proteins by which S-nitrosylation can modulate NO availability with a potential impact on PE.

A Big Role for microRNAs in Gestational Diabetes Mellitus.

Maternal diabetes is associated with pregnancy complications and poses a serious health risk to both mother and child. Growing evidence suggests that pregnancy complications are more frequent and severe in pregnant women with pregestational type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) compared to women with gestational diabetes mellitus (GDM). Elucidating the pathophysiological mechanisms that underlie the different types of maternal diabetes may lead to targeted strategies to prevent or reduce pregnancy complications. In recent years, microRNAs (miRNAs), one of the most common epigenetic mechanisms, have emerged as key players in the pathophysiology of pregnancy-related disorders including diabetes. This review aims to provide an update on the status of miRNA profiling in pregnancies complicated by maternal diabetes. Four databases, Pubmed, Web of Science, EBSCOhost, and Scopus were searched to identify studies that profiled miRNAs during maternal diabetes. A total of 1800 articles were identified, of which 53 are included in this review. All studies profiled miRNAs during GDM, with no studies on miRNA profiling during pregestational T1DM and T2DM identified. Studies on GDM were mainly focused on the potential of miRNAs to serve as predictive or diagnostic biomarkers. This review highlights the lack of miRNA profiling in pregnancies complicated by T1DM and T2DM and identifies the need for miRNA profiling in all types of maternal diabetes. Such studies could contribute to our understanding of the mechanisms that link maternal diabetes type with pregnancy complications.

Thrombocytopenia in Pregnancy: A Cross-Sectional Study in Northern Pakistan

Objective: To determine the association of thrombocytopenia (mild, moderate &amp; severe) with pregnancy-related disorders.&#x0D; Study Design: Cross-sectional study.&#x0D; Place and Duration of Study: Department of Haematology of Pakistan Railway Hospital, Rawalpindi Pakistan, in collaboration with the Departments of Obstetrics and Gynecology of Pak Emirates Military Hospital and Fuji Foundation Hospital, Rawalpindi Pakistan, from Oct 2018 to Oct 2019.&#x0D; Methodology: Seventy-five pregnant females with platelet count &lt;150x109/l were included. Blood samples were taken and analyzed for complete blood count, peripheral blood smear, manual count by Neubauer chamber, uric acid, urinary proteins, liver function tests (bilirubin &amp; aspartate aminotransferase), lactate dehydrogenase, coagulation profile and viral serology (Hepatitis B &amp; C).&#x0D; Results: Out of a total of 75 thrombocytopenic pregnant females, gestational thrombocytopenia was most common (74.7%), followed by preeclampsia (17.3%), HELLP syndrome (4%), immune thrombocytopenic purpura (4%) respectively. Mild thrombocytopenia was frequently observed in patients of G.T. (62.5%), while moderate thrombocytopenia (84.6%) was generally detected in preeclampsia patients. Severe thrombocytopenia was mostly identified in patients with HELLP syndrome (66.7%) and immune thrombocytopenic purpura (66.7%).&#x0D; Conclusion: Mild thrombocytopenia is mostly presented in gestational thrombocytopenia. Moderate thrombocytopenia was frequent in patients with preeclampsia, and severe thrombocytopenia was usually diagnosed in patients with HELLP syndrome and immune thrombocytopenic purpura, which require apposite and judicious management for the safety of mother and fetus.

Spontaneous Rupture of Renal Cell Carcinoma in Pregnancy: A Case Report

Renal cell carcinoma is the most common type of malignancy in pregnancy. Rupture of renal cell carcinoma is not uncommon. The diagnosis of renal cell carcinoma is often delayed as the clinical presentation might resemble other pregnancy-related disorders or asymptomatic in most cases and a complete ultrasonographic examination of the abdomen is not a part of the routine obstetric evaluation. We report a rare case with spontaneous rupture of renal cell carcinoma in 20 years old in full-term pregnancy primigravida presented by hypertensive disorder and severe abdominal pain with massive retro peritoneum collection, radical nephrectomy was done and the patient life was saved.

Preeclampsia and COVID-19: the Role of Inflammasome Activation.

Purpose of ReviewIt is well established that controlled immune activation and balance is critical for women’s reproductive health and successful pregnancy outcomes. Research in recent decades in both clinical and animal studies has demonstrated that aberrant immune activation and inflammation play a role in the development and progression of women’s reproductive health and pregnancy-related disorders. Inflammasomes are multi-protein cytoplasmic complexes that mediate immune activation. In this review, we summarize current knowledge on the role of inflammasome activation in pregnancy-related disorders.Recent FindingsIncreased activation of inflammasome is associated with multiple women’s health reproductive disorders and pregnancy-associated disorders, including preeclampsia (PreE). Inflammasome activation is also associated with the novel coronavirus disease 2019 (COVID-19) disease caused by the SARS-Cov-2 virus. We and others have observed a positive association between increased PreE incidences with the onset of the COVID-19 pandemic. Here, we present our recent data indicating increased inflammasome activation, represented by caspase-1 activity, in women with COVID-19 and PreE compared to normotensive pregnant women COVID-19.SummaryThe role of inflammation in pregnancy-related disorders is an area of intense research interest. With the onset of the COVID-19 pandemic and the associated increase in PreE observed clinically, there is a greater need to identify mechanisms of pathophysiology and targets to treat this maternal disorder. Inflammasome activation is associated with PreE and COVID-19 infection and may hold therapeutic potential to improve outcomes associated with PreE and curb the morbidity attributed to PreE.

The Role of Kisspeptin in the Pathogenesis of Pregnancy Complications: A Narrative Review.

Kisspeptins are the family of neuropeptide products of the KISS-1 gene that exert the biological action by binding with the G-protein coupled receptor 54 (GPR54), also known as the KISS-1 receptor. The kisspeptin level dramatically increases during pregnancy, and the placenta is supposed to be its primary source. The role of kisspeptin has already been widely studied in hypogonadotropic hypogonadism, fertility, puberty disorders, and insulin resistance-related conditions, including type 2 diabetes mellitus, polycystic ovary syndrome, and obesity. Gestational diabetes mellitus (GDM), preeclampsia (PE), preterm birth, fetal growth restriction (FGR), or spontaneous abortion affected 2 to 20% of pregnancies worldwide. Their occurrence is associated with numerous short and long-term consequences for mothers and newborns; hence, novel, non-invasive predictors of their development are intensively investigated. The study aims to present a comprehensive review emphasizing the role of kisspeptin in the most common pregnancy-related disorders and neonatal outcomes. The decreased level of kisspeptin is observed in women with GDM, FGR, and a high risk of spontaneous abortion. Nevertheless, there are still many inconsistencies in kisspeptin concentration in pregnancies with preterm birth or PE. Further research is needed to determine the usefulness of kisspeptin as an early marker of gestational and neonatal complications.

Prevention of Gestational Diabetes Mellitus and Gestational Weight Gain Restriction in Overweight/Obese Pregnant Women: A Systematic Review and Network Meta-Analysis.

Background: Overweight/obesity is associated with pregnancy-related disorders, such as gestational diabetes mellitus (GDM) and excessive gestational weight gain (GWG). Although multiple interventions have been proposed to prevent GDM and restrict GWG, our knowledge of their comparative efficacy is limited. Objective: To evaluate the effectiveness and identify the optimal intervention strategy to prevent GDM and restrict GWG among overweight/obese pregnant women. Methods: Randomized controlled trials that recruited overweight/obese pregnant women at <20 gestational week were obtained. Predictive and confidence interval plot and surface under the cumulative ranking (SUCRA) were performed using Stata statistical software to determine and compare the efficacy of interventions (diet, physical activity (PA), diet + PA intervention and medication). Results: 23 studies with a total of 8877 participants were eligible for analysis. Our results indicated that although neither PA, diet + PA, diet nor medication intervention could significantly protect overweight/obese women from the development of GDM, there was a trend that PA and diet + PA intervention were preventive factors of GDM. Of these, PA intervention (SUCRA, 82.8%) ranked as the superior strategy, and diet intervention (SUCRA, 19.7%) was the least efficacious regimen. Furthermore, interventions of diet, PA and diet + PA were significantly beneficial for GWG restriction, whereas medication intervention could not restrict GWG. In detail, diet intervention (SUCRA, 19.7%) ranked as the optimal regimen, whilst PA intervention (SUCRA, 62.3%) ranked as the least efficacious regimen. Conclusion: Although none of the interventions could offer remarkable benefit for GDM prevention, interventions of diet, PA and diet + PA were significant factors to restrict GWG. In aggregate, diet + PA intervention seemed the superior choice for the prevention of both GDM and excessive GWG. Registration: PROSPERO CRD42022313542.

The Diagnostic Potential of Gut Microbiota-Derived Short-Chain Fatty Acids in Preeclampsia.

Preeclampsia (PE) is a complex pregnancy-related hypertensive disorder leading to multiorgan dysfunction. It has high maternal, fetal, and neonatal morbidity and mortality rates. The study of gut microbiota and its metabolites in PE deserves further exploration. Thirty-eight pregnant women with PE and 29 healthy pregnant women in the third trimester of their pregnancy were recruited in this study. We used a targeted metabolomics approach to evaluate the short-chain fatty acids (SCFAs) in serum samples. The correlation between SCFAs and clinical characteristics was also explored. The results of mass spectrometry (MS) showed significant differences at the metabolomics level of SCFAs between the PE and healthy control. The metabolic levels of acetate, propionate, isobutyrate, and valerate were significantly increased in the PE group than in the healthy control group. In contrast, caproic acid and butyrate levels were significantly reduced. The correlation analysis showed that urea, systolic, and diastolic blood pressure levels were positively correlated with four types of SCFAs (acetic acid, propionic acid, isobutyric acid, and valeric acid) which increased in the PE group. Furthermore, the neutrophil percentage and the fetal birth weight were negatively correlated with isobutyric acid and valeric acid. In addition, the receiver operating characteristic (ROC) analysis using a generalized linear model showed that multiple SCFAs would be potential diagnostic markers for PE, with high specificity, sensitivity, and area under the curve (AUC). Among them, isobutyric acid (sensitivity: 97.4%, specificity: 100%, AUC = 1.00), propionic acid (sensitivity: 86.8%, specificity: 93.3%, AUC = 0.954) and acetic acid (sensitivity: 86.8%, specificity: 83.3%, AUC = 0.891) depicted significantly higher diagnostic value and potential clinical applications. In summary, the results of this study indicate that SCFAs have the potential to become effective biomarkers for early screening of PE.

Downregulation of miR-1270 mediates endothelial progenitor cell function in preeclampsia: Role for ATM in the Src/VE-cadherin axis.

Preeclampsia, a pregnancy-related hypertensive disorder, is associated with endothelial dysfunction and increased cardiovascular risk of the offspring in adulthood. In preeclampsia, endothelial colony-forming cells (ECFC) are reduced in number and function. Recently, we have shown that miR-1270, which is involved in cancer in vitro proliferation, migration, and tumor progression, is downregulated in fetal ECFC from preeclamptic pregnancies. We now hypothesize that miR-1270 dysregulation contributes to vascular endothelial dysfunction occurring after preeclampsia via ATM (ataxia telangiectasia mutated) overexpression, the key kinase of DNA damage repair. Here, we show that miR-1270silencing in normal ECFC and downregulation in preeclamptic ECFC are accompanied by an increase in the expression levels of ATM. Furthermore, ATM activation correlates with upregulated tyrosine kinase Src leading to phosphorylation and internalization of VE-cadherin (vascular endothelial-cadherin) which subsequently compromises endothelial barrier permeability and morphodynamic cell parameters. Treatment with specific ATM inhibitors reveals a novel role of ATM upstream of tyrosine kinase Src activation. Subsequently, Src phosphorylation and internalization of VE-cadherin compromise endothelial barrier permeability. Our findings suggest that downregulation of miR-1270 contributes to impaired ECFC function via the associated ATM overexpression, which further identifies ATM as a novel and critical factor for ECFC defects in preeclampsia. Our study provides new insights into the understanding of ECFC impairment associated with cardiovascular risk in preeclamptic offspring and identifies potential novel therapeutic targets.

Maternal Vitamin D, Oxidative Stress, and Preeclampsia

(Int J Gynecol Obstet. 2021;154:444–450) Preeclampsia (PE) is a serious and complex pregnancy-related disorder with negative effects on both the mother and fetus. Prevention is vital to reduce 18% of maternal mortality that results from PE in the United States each year. After years of study, its causes and mechanisms have not yet been fully unraveled. A recent review and analysis have shown an association between maternal vitamin D levels during pregnancy and an increased risk of PE.

Erythrocyte membrane-camouflaged nanoparticles as effective and biocompatible platform: Either autologous or allogeneic erythrocyte-derived.

Erythrocytes are often used for the development of cell membrane camouflaged nanoparticles (NPs) due to their wide range of sources. However, whether the difference between autologous and allogeneic sources for the erythrocyte membranes have an influence on the performance of camouflaged NPs, which is still inconclusive. To this end, we developed two aggregation-induced emission (AIE) photosensitizers camouflaged with erythrocyte membranes (E-M), named E-Mauto@P and E-Mallo@P, which were prepared using autologous- and allogeneic-derived erythrocytes, respectively. In vivo, E-M@P-mediated photodynamic therapy (PDT) effectively inhibited tumor growth, and this therapeutic effect did not differ between E-Mauto@P and E-Mallo@P. Importantly, there were no differences between E-Mauto@P and E-Mallo@P treated mice in terms of general condition, organ function or immune system. Both E-Mauto@P and E-Mallo@P have been shown not to cross the placental barrier and do not affect the development of the embryo, which could be a good platform for the treatment of pregnancy-related disorders. These findings provided more detailed evidences for erythrocyte membrane camouflaged NPs as a promising therapeutic platform, since there is no difference in efficacy or biosafety of either autologous or allogeneic erythrocyte-derived NPs.

Fetomaternal Cardiovascular and Renal Adverse Outcomes of Recurrent Preeclampsia in Rats

Preeclampsia (PE) is a serious pregnancy‐related disorder associated with considerable maternal and neonatal morbidity. Preeclamptic women have increased risk of PE recurrency during subsequent pregnancies. Clinically, recurrent PE is accompanied by more frequent maternal and fetal complications compared with the initial PE episode. Here, we investigated the impact of recurrent PE episode on the cardiovascular and renal profiles of female rats and their offspring. PE was induced by oral L‐NAME administration (50 mg/kg/day, gestation days 14‐21) for either single pregnancy or two consecutive pregnancies. Maternal and fetal abnormalities were compared with corresponding pregnancy controls. Recurrent and single PE caused similar increases in systolic blood pressure of mothers over last week of pregnancy and decreases in average weight of pubs. However, recurrent PE was associated with new onset elevation in renovascular reactivity to vasoconstrictors (phenylephrine and angiotensin II) compared with normal renal vasoconstriction in single PE dams. By contrast, the single, but not recurrent, PE was coupled with renal hypo‐reactivity to acetylcholine vasodilations. Examination of male and female progenies of single PE mothers revealed significant rises in blood pressure and renal vasodilatory dysfunction in female, but not male, offspring. Nevertheless, the attenuation in renovascular responsiveness to phenylephrine and angiotensin II was noted in both genders. Collectively, these data indicate that recurrent PE is associated with alleviation of single PE renal vasodilatory impairment as well as new onset hyperreactivity to vasoconstrictors. The results also highlight sexual dimorphism in the impact of PE on cardiovascular and renal profiles of the progeny. Future studies will be conducted to assess whether such sex‐related differences persist in the offspring of recurrent PE mothers.