Normal Pregnancy Research Articles

Differential expression of immune checkpoints (OX40/OX40L and PD-1/PD-L1) in decidua of unexplained recurrent spontaneous abortion women

In this study, we aimed to investigate the expression of OX40, OX40L, PD-1 and PD-L1 in patients with unexplained recurrent spontaneous abortion (URSA) compared to normal pregnancies (NP). A total of 50 patients who were diagnosed with URSA and 41 NP were recruited to this study. Real-time polymerase chain reaction (RT-PCR) was used to determine the expression of OX40, OX40L, PD-1 and PD-L1 in decidual tissues; Immunohistochemistry (IHC) was conducted to characterize the distribution of the involved genes in decidual tissues; Double immunofluorescence staining was used to prove the localization of the involved genes in decidual tissues. The concentrations of OX40L and PD-L1 in plasma were measured with enzyme-linked immunosorbent assay (ELISA). The expression of OX40L in the decidua of URSA patients was significantly increased compared to that in the NP group, while the expression of PD-L1 in the URSA group was decreased compared to that in the NP group. Both proteins are localized in the decidual stroma as analyzed by double immunofluorescence staining. The staining results were confirmed at the mRNA level of decidual tissues, while the mRNA level of peripheral blood showed no significant difference. In conclusion, the results suggest that decidual stromal cells may promote the interaction with OX40 on T cells by upregulating the expression of OX40L and reduce the interaction with PD-1 on T cells by downregulating the expression of PD-L1 in URSA patients, which may interfere with the immune tolerance of the maternal-fetal interface, leading to poor pregnancy outcomes.

COMPARISON OF OXIDATIVE STRESS LEVELS DURING THE THIRD TRIMESTER IN NORMAL PREGNANCY AND PREECLAMPSIA

Background: The placenta is a complex transiently formed organ which plays a crucial role in the development of the foetus. As the placenta is responsible for maintaining pregnancy placental defects are mainly responsible for pregnancy-related issues. Preeclampsia is a pregnancy-related disorder due to uteroplacental insufficiency resulting from deficient remodelling of spiral arteries causing ischemic reperfusion injury which is finally responsible for the generation of reactive oxygen species and oxidative stress by the placenta. So, this study was planned to determine and compare serum levels of oxidative stress markers (ischemia-modified albumin and malondialdehyde) in preeclampsia and normal pregnancy in the third trimester. Methods: Study design: Cross-sectional comparative study Settings Gynae/Obs Department and Pathology Laboratory, Lahore General Hospital, Lahore. Study population: 42 Pregnant females at 34–36 weeks of gestation were selected. Group 1 compromised 21 normal healthy pregnant females and group 2 included 21 preeclamptic patients. Sampling technique: non-probability purposive sampling. Blood samples were taken at 34–36 weeks of gestation. Serum was stored for ischemia-modified albumin and malondialdehyde. Data was analyzed using SPSS version 20. An Independent t-test was used to compare values between the groups during the third trimester. A p-value of ≤0.05 was considered significant. Results: Comparison of ischemia-modified albumin and malondialdehyde values between group I and group 2 showed a highly significant difference of p-value of <0.001. Conclusion: Oxidative stress markers were higher in preeclamptic patients as compared to normal pregnant females during the third trimester suggesting the role of the placenta in oxidative stress.

Volatile Organic Compounds Detected in Amniotic Fluid of Women During Normal Pregnancy

AbstractExposure to volatile organic compounds (VOCs) during the fetal period may induce negative effects on children’s health (e.g. increased risk of low birth weight and imbalanced development). Whereas VOCs have been analysed extensively in various human biological fluids (i.e. urine, blood, and breath), during pregnancy only urine has been studied and no work has been performed on amniotic fluid (AF), which is in direct contact with the fetus and is essential for its well-balanced development and maturation. This study aimed to detect VOCs in AF and to investigate their links to the lifestyle habits of pregnant women. The VOC composition of the AF collected from 76 healthy pregnant women was analysed using a gas chromatograph coupled to a mass spectrometer. The sources of VOC exposure in pregnant women were assessed using a questionnaire about their home living conditions and their professional exposure. A total of 126 VOCs belonging to 13 chemical families were detected in AF. The majority of these VOCs (92) had an exogenous origin, and their presence was linked to lifestyle habits, especially smoking and fragrance use. Considering the direct contact of these VOCs with multiple fetal organs, this study is an important contribution to the literature exploring the future potential relationships between VOCs and abnormal fetal development.

A study of the effect of hypothyroidism during pregnancy on human milk quality based on rheological properties

Hypothyroidism has been found to have an effect on the nutritional composition of human milk during pregnancy. This study aims to explore the combined influence of rheological properties, macronutrient content, particle size, and the zeta potential of milk fat globules, as well as the composition of milk fat globule membrane (MFGM) proteins on the quality of human milk in gestational hypothyroidism. The study revealed that human milk from the group with hypothyroidism during pregnancy (AHM) was less viscoelastic and stable when compared with normal pregnancy group human milk (NHM). Furthermore, the particle size and macronutrient content of NHM were found to be larger than that of AHM. In contrast, the zeta potential of AHM was greater than that of NHM. The sodium dodecyl sulfate-PAGE results disclosed that the composition of MFGM proteins in these 2 groups were generally the same, but the content of AHM was lower than that of NHM. In conclusion, this study confirms that hypothyroidism during pregnancy can have a significant effect on the quality of human milk.

Role of growth differentiation factor-15 (GDF-15) in missed miscarriage and its relationship to oxidative stress markers

Aim. The study aimed to investigate the level of growth differentiation factor-15 (GDF-15) and its relationship to markers of oxidative stress (OS) as predictors of missed miscarriage (MM).
 Materials and methods. A prospective cohort study of 80 females was conducted. The main group included 40 patients with MM at 5–9 weeks of gestation; the control group included 40 females with elective termination at the same gestation period. OS markers, including malonic dialdehyde, carbonyl groups of proteins, and the superoxide dismutase antioxidant enzyme, as well as the GDF-15, were measured in serum, aspiration fluid, and chorionic tissues in women with normal pregnancy and MM at 5–9 weeks of gestation.
 Results. The results showed that the complex balance maintained between the production of reactive oxygen species and antioxidant activity in MM is shifted towards oxidative reactions (p0.05) and is associated with non-enzymatic lipid peroxidation, and OS can become a leading factor in the pathogenesis of MM. The GDF-15 levels were significantly higher in aspiration fluid and chorionic tissues in patients of the study groups; low concentrations of GDF-15 in MM patients in aspiration fluid and chorionic tissues highlight the role of this protein as an important regulator of proinflammatory molecules (p0.05). In addition, a decrease in the GDF-15 level negatively correlates with OS markers, such as malonic dialdehyde and the superoxide dismutase antioxidant enzyme, suggesting the role of this cytokine in peroxidation and OS development.
 Conclusion. The study of biomarkers of independent pathological pathways as predictors of miscarriage will allow clinicians to stratify and predict the risks of early reproductive loss more accurately.

The Prl3d1-Cre mouse line selectively induces the expression of Cre recombinase in parietal trophoblast giant cells.

The placenta plays a pivotal role in the maintenance of normal pregnancy, but how it forms, matures, and performs its function remains poorly understood. Here, we describe a novel mouse line (Prl3d1-iCre) that expresses iCre recombinase under the control of the endogenous prl3d1 promoter. Prl3d1 has been proposed as a marker for distinguishing trophoblast giant cells (TGCs) from other trophoblast cells in the placenta. The in vivo efficiency and specificity of the Cre line were analyzed by interbreeding Prl3d1-iCre mice with B6-G/R reporter mice. Through anatomical studies of the placenta and other tissues of Prl3d1-iCre/+; B6-G/R mouse mice, we found that the tdTomato signal was expressed in parietal trophoblast giant cells (P-TGCs). Thus, we report a mouse line with ectopic Cre expression in P-TGCs, which provides a valuable tool for studying human pathological pregnancies caused by implantation failure or abnormal trophoblast secretion due to aberrant gene regulation.

Assessment of endothelial function in pregnant women with normal pregnancy and pregnancy complicated by hypertensive disorders

Objective. To assess the vascular endothelial function in the first trimester of pregnancy using the method of skin thermometry in the aspect of the development of hypertensive complications.
 Materials and methods. One hundred women in the first trimester of pregnancy were examined. Based on the gestation outcomes they were divided into two groups: group 1 consisted of 80 patients without pregnancy complications, group 2 included 20 women whose pregnancy was complicated by hypertensive disorders. Clinical and anamnestic risk factors were evaluated; blood pressure level, uterine artery pulsation index, pregnancy-associated plasma protein A were measured; endothelial function was assessed using high-resolution skin thermometry.
 Results. Analysis of the obtained data showed significant differences in the body mass index, systolic and diastolic blood pressure levels and values of pulsation index in the uterine arteries. An increase in the indicators during the first trimester of pregnancy was observed in patients from the group with hypertensive disorders. The results of measurements of blood flow fluctuations in the microcirculatory system showed no significant differences in the compared groups.
 Conclusions. The obtained results of measuring the amplitudes of blood flow fluctuations in the microcirculatory system indicate the absence of initial endothelial dysfunction in the maternal body. However, an increase in the body weight, initial level of systolic and diastolic blood pressure, uterine artery pulsation index have an important role in predicting the development of hypertensive disorders in pregnancy.

Effect of Meconium Stained Liquor on Mode of Delivery and Fetomaternal Outcome in a Tertiary Level Hospital

Background: The appearance of meconium-stained liquor during labour is generally considered to be a sign of hypoxia and a predictor of poor fetal outcome.It is one of the clinical events where normal pregnancy can turn into a high risk one for the mother as well as for the foetus.
 Objective: To evaluate the obstetric outcome in meconium stained liquor during labour.
 Study design: Prospective comparative study.
 Study setting and period: Gynaecology and Obstetrics department of Sir Salimullah Medical College and Mitford Hospital (SSMC and MH), Dhaka, between January 2019 to June 2019.
 Study population: The study patients in labour with meconium stained amniotic fluid and women in labour but having clear amniotic fluid who admitted for delivery during study period.
 Result: A total 75 cases were enrolled in the study as case and 75 cases were enrolled as control. The mean age was found 29.14±5.59 years in case group and 28.9±6.2 years in control group. Patients received irregular ANC was 20(26.7%) and 25(33.3%) in case and control group respectively. Patients who did not receive ANC was 24(32.0%) in case group and 12(16.0%) in control group. Mean gestational age at delivery was found 38.87±1.4 weeks in case group and 38.75±1.6 weeks in control group. Primigravida was predominant in both groups. Caesarean deliveries were high (80.0%) in cases and it was much higher with thick meconium (74.7%) as compared to thin meconium (25.3%). APGAR scores in first minute and fifth minute were also low in cases. Birth asphyxia was found 20.0% in case group and 6.3% in control group. Meconium aspiration syndrome 25.0% and convulsion 3.8% developed only in cases. Neonatal ward admission was 22.0% in case group and 6.3% in control group. Neonatal mortality was higher (3.8%) in cases than control 1.3%. Majority (6.65%) patients had post partum hemorrhage in case group and 3(4.0%) in control group.
 Conclusion: Meconium stained amniotic fluid were associated with higher rate of caesarian delivery, increased need for neonatal resuscitation, increased rate of birth asphyxia with hypoxic ischemic encephalopathy, meconium aspiration syndrome, hospital admission, and mortality. Electronic foetal monitoring, timely obstetrical intervention and neonatal care can reduce associated complications and improve foetal outcome.
 J Shaheed Suhrawardy Med Coll 2022; 14(1): 43-49

Changes in Serum Concentrations of Bone Turnover Markers in Healthy Pregnant Women.

Changes in bone metabolism during pregnancy have not received sufficient attention because of the lack of effective screening tools. Bone turnover markers (BTMs) could reflect the changes of bone metabolism. Currently, reference intervals for bone metabolism during normal pregnancy are inconclusive. This study aimed to determine reference intervals for BTMs in pregnant women taking prenatal care and to facilitate clinical research on diseases affecting bone metabolism during pregnancy. We surveyed 120 low-risk pregnant women attending routine antenatal care from January 2020 to March 2020. The serum levels of procollagen type I N-propeptide (PINP), N-terminal osteocalcin (N-MID), and C-terminal telopeptide of type I collagen (β-CTX) were measured in the first trimester (<13 weeks), second trimester (14-27 weeks), and third trimester (>28 weeks). Reference intervals for BTMs during pregnancy were analyzed. The Kruskal-Wallis test and paired t-test are used to analyze differences between groups. Spearman correlation coefficients expressed the measure of linear association. The bone resorption marker β-CTX in third trimester increases compared to the first trimester and the second trimester (P < 0.001, P < 0.001). The bone formation markers PINP and N-MID were decreased from the first trimester to the second trimester (P = 0.01, P < 0.001) and then raised from the second trimester to the third trimester (P < 0.001, P < 0.001). Two indices of bone turnover rate, β-CTX/PINP and β-CTX/N-MID, were increased from the first trimester to the second trimester (P < 0.001, P < 0.001) and then decreased from the second trimester to the third trimester (P = 0.02, P < 0.001). This study established reference intervals for BTMs in pregnant women and observed the changes in BTMs during the different trimesters of pregnancy. The present findings can help in clinical monitoring of the effects of pregnancy diseases on the bone metabolism of pregnant women.

Cytology Techniques Can Provide Insight into Human Placental Structure Including Syncytiotrophoblast Nuclear Spatial Organisation.

The aim of this study was to provide the first systematic description of human placental cytology appearances and to investigate syncytiotrophoblast nuclear organisation patterns using cytology techniques. Term placentas from normal pregnancies were sampled using fine-needle aspiration (FNA) and direct scrapes. Standard histological examination was also performed to exclude pathological changes in the placentas being studied. Both Papanicolaou-stained cytospin preparations and air-dried Giemsa slides from FNA provided high-quality material for cytological assessment with good cellularity. Among the key features of the cytology preparations were villous "microbiopsies" that allowed for the three-dimensional appreciation of villous branching patterns. Cytological appearances, including nuclear characteristics of villous cytotrophoblast and syncytiotrophoblast, were also well demonstrated. In microbiopsies and detached villous trophoblast sheets, complex patterns of syncytiotrophoblast nuclear organisation, not previously described cytologically, were observed, including irregular spacing of nuclei, syncytioplasm windows and linear nuclear arrangements. This study showed that placental cytology (a) provides technically excellent material for cytological evaluation, (b) confirms the presence of complex nuclear organisational patterns in the syncytiotrophoblast by eliminating the possibility of tangential sectioning artefact, (c) provides superior nuclear detail over standard histological sections and (d) may be an untapped research resource for the investigation of normal and pathological processes because of its ability to look at the placenta in a novel way and through its potential for both ex vivo and in vivo placental sampling.

Relationship between Maternal ABO Blood group and pregnancy complications of adichunchanagiri hospital B.G Nagara -A cross sectional study

ABO blood group has been divulged as a risk factor for perceptible diseased states. The ABO blood group differences may put a patient at specific risk according to their inherited antigens among the obstetrical syndromes like Intrauterine growth restriction, Pre-eclampsia and pre-term labour. Studies conducted have shown Group O individuals had lowest plasma von Willebrand factor and non O group had elevated level of this factor which showed increased thrombotic risk among these individuals. The earlier studies conducted have focused only on preeclampsia but not on other complications of pregnancy and the data available is scarce. The study aims to determine whether maternal ABO blood groups contribute to adverse pregnancy outcomes especially in this part of the country.The study was conducted on 50 pregnant women who were having complications of pregnancy including preeclampsia (PE), cases of Pregnancy induced hypertension (PIH), Gestational Diabetes mellitus (GDM) were considered as study cases and 50 pregnant women with normal pregnancy without any complications were categorized as controls. The study was conducted for a period of 6 months among patients attending Obstetrics and Gynecology department of Adichunchanagiri hospital selected based on convenience sampling procedure. Maternal ABO Blood group of the subjects were determined by Haemagglutination technique.Relationship between maternal ABO Blood group and Pregnancy complications (PE, PIH.GDM) was estimated by calculating odds ratio from logistic regression models using Blood Group O as a reference group and p – value of &amp;#60; 0.05 was considered as statistically significant. The results of the present study have found that maternal AB blood group was highest among preeclampsia and PIH category of cases.The present study conducted have found maternal AB blood group was highest among PIH and preeclampsia category of casesFrom the study conducted we want to conclude non-O blood group had the highest risk compared to O Blood group among pregnancy complications.

The effectiveness of assisted reproductive technologies immunological prediction

The high frequency of infertility is a significant medical and social problem in many countries of the world; assisted reproductive technologies (ART) are actively used to solve it. Given that immune responses play an important role in the development and maintenance of pregnancy, the study of changes in immune parameters is relevant in different trimesters of pregnancy, as well as at the stage of preconception preparation. It is believed that the maternal-fetal relationship is not limited to the development of maternal tolerance to fetal antigens, but is complemented by complex cytokine interactions that control selective immune regulation, control of adhesion and vascularization processes during embryo implantation and pregnancy. The purpose of the review was to analyze the available scientific data on the use of immune parameters to predict the effectiveness of ART. A review of Russian and foreign scientific papers on prevalence, immunopathogenetic mechanisms, and infertility diagnostics was carried out. A multi-criteria search was carried out for inventions, abstracts of patent documents on immunological prediction of the effectiveness of ART. As predictors, immunocompetent cells (CD3+-, CD4+-, CD3-CD16+56+-venous blood lymphocytes, CD95+ macrophages of endometrial biopsy), cytokines, pregnancy glycoproteins, autoantibodies, immunogenetic markers are presented. The study of the quantitative level of cytokines in blood serum, ovarian follicular fluid and endometrium as mediators of intercellular and intertissue interactions is of undoubted scientific and practical interest in terms of establishing their discriminatory levels specific to different trimesters of a normal pregnancy, the threat of miscarriage, and infertility. There was an association with non-occurrence of pregnancy due to in vitro fertilization of an increased content of interleukin (IL)-2 and interferon (IFN)-γ in the follicular fluid, and a soluble receptor IL-2-α, IL-8 and lactoferrin in the blood serum. The immunosuppressive effects of pregnancy-associated α2-glycoprotein, trophoblastic β1-glycoprotein, α-fetoprotein, α2-macroglobulin contribute to the development and maintenance of pregnancy, but their prognostic value is not unambiguous. The study of the content of immunoglobulins G to α2-macroglobulin, lactoferrin, progesterone, estradiol, cardiolipin in the follicular fluid and blood serum makes it possible to predict the result of ART. Conclusion. The study of immune parameters, especially in combination with sex hormones and characteristics of the state of the embryo, in infertile women has diagnostic value and prognostic significance, and can contribute to the timely correction of therapy and the ART program.

An examination of the seroprevalence of torch infections and their correlation with adverse reproductive outcomes in females exhibiting a bad obstetric history

: The term TORCH infections refer to a group of diseases including Toxoplasma, Other (syphilis, varicella-zoster, parvovirus B19), Rubella, Cytomegalovirus (CMV), and Herpes infections. These are a set of pathogens capable of traversing the placental barrier, subsequently causing congenital infections. Often these infections are asymptomatic initially and pose significant diagnostic challenges during gestation, potentially leading to undesirable obstetric outcomes. This research intends to explore the correlation between TORCH infections and perinatal outcomes within pregnancies deemed high-risk.: We examined 143 high-risk pregnant patients aged 18-46 from the Obstetrics and Gynecology Department at the Baghdad Gynecology and Obstetrics Hospital. Hundreds of normal pregnancy group were also included. The high-risk group encompassed women with recurring pregnancy loss, fetal congenital anomalies, intrauterine fetal death, and low birth weight intrauterine neonatal death. The presence of IgG and IgM antibodies against TORCH agents in patients’ serum control serum were assessed using ELISA kits. We compared perinatal outcomes between TORCH seropositive and seronegative high-risk pregnant women.: Among the 143 high-risk pregnancies, a significant proportion of young, low-parity women from diverse residences were co-seropositive for Toxoplasma gondii, rubella virus, Cytomegalovirus, and Herpes Simplex infections. Of these, 55 cases (48.4%) were seropositive for all the four TORCH agents compared to 88 cases (38%) were seropositive for antibodies to one to three of the TORCH agents. IgG seropositivity was 74.5%, while IgM seropositivity was 31.8% for Toxoplasma gondii, 3.6% for CMV and 0% for RV infections, respectively. Significantly, high-risk pregnancies with TORCH seropositivities exhibited a clearly strong correlation with Habitual abortions outcomes.: High-risk manifestations demonstrated for Toxoplasma gondii, Rubella virus, Cytomegalovirus and Herpes Simplex infections strongly associated with habitual abortions compare to high but less significant association in those seropositive to one, two or three of the TORCH agents

Immune Responses Potentially Involved in the Gestational Complications of Brucella Infection.

Infection by Brucella species in pregnant animals and humans is associated with an increased risk of abortion, preterm birth, and transmission of the infection to the offspring. The pathogen has a marked tropism for the placenta and the pregnant uterus and has the ability to invade and replicate within cells of the maternal-fetal unit, including trophoblasts and decidual cells. Placentitis is a common finding in infected pregnant animals. Several proinflammatory factors have been found to be increased in both the placenta of Brucella-infected animals and in trophoblasts or decidual cells infected in vitro. As normal pregnancies require an anti-inflammatory placental environment during most of the gestational period, Brucella-induced placentitis is thought to be associated with the obstetric complications of brucellosis. A few studies suggest that the blockade of proinflammatory factors may prevent abortion in these cases.

Twenty-four-hour urinary protein excretion in uncomplicated singleton pregnancy

Twenty-four-hour urinary total protein excretion is an essential parameter used for evaluation of renal function and early detection of gestational complications. However, data on reference ranges of 24-hour urinary total protein excretion in normal pregnancy are scarce. This study aimed to determine reference ranges for 24-hour urinary total protein excretion in a population with uncomplicated singleton pregnancies using a standard method for urinary total protein. In addition, the values of 24-hour urinary total protein were stratified by maternal age and prepregnancy body mass index. This study was based on a prospective cohort study in Shenzhen, China. The pregnant women were enrolled at their first prenatal clinical visit. All the participants were instructed to collect 24-hour urine samples during the following successive gestational periods: 6+0 to 13+6, 14+0 to 27+6, and 28+0 to 41+6 weeks. Total urinary protein excretion was analyzed by a colorimetric method. Ultimately, the study encompassed a total of 4844 pregnant women with uncomplicated pregnancies. The nonparametric percentile method was used to determine reference ranges for 24-hour urinary total protein excretion during different trimesters in women with uncomplicated pregnancies (excluding those with previous kidney disorders, gestational or chronic hypertension, preeclampsia, and pregestational diabetes mellitus, among others). The 24-hour urinary total protein levels expressed as medians and percentiles (5th, 95th) for each trimester were as follows: 72.0 (28.4, 165.0), 88.0 (34.0, 185.0), and 108.0 (37.5, 258.0) mg in the first, second, and third trimesters, respectively. A significant increase in 24-hour urinary total protein excretion was observed throughout pregnancy (all P values <.001). Moreover, 24-hour urinary total protein levels were higher in the older (≥35 years) than in the younger (<35 years) group from mid-gestation. Specifically, the median (interquartile range) 24-hour urinary total protein levels by age were 72.2 (50.6-100.0) vs 70.5 (50.5-100.0) mg, 85.8 (62.0-117.0) vs 96.0 (68.0-127.8) mg, and 106.6 (76.0-146.2) vs 114.7 (81.5-153.6) mg in the first, second, and third trimesters, respectively. In addition, 24-hour proteinuria was significantly increased in higher-weight (overweight or obese) subgroups compared with lower-weight (underweight or normal-weight) subgroups (all P values <.05). Our study provides reference values for 24-hour urinary total protein excretion with apparently uncomplicated pregnancies. Understanding these changes in low-risk pregnancies is essential for optimizing maternal management.

Proteomic analysis of N-glycosylation of the human placenta between preeclampsia and normal pregnancies

Protein N-glycosylation plays critical roles in modulating placental function, but little is known about N-glycoproteins in the human placenta and modifications in preeclampsia (PE). Here, we show a large, site-specific N-glycoproteome profiling study of PE and normal placenta using quantitative N-glycoproteomics based on mass spectrometry. The study identified disease signatures of altered N-glycoproteins and N-glycosylation site occupancy in PE and provided a system-level view of human placental N-glycoproteins and in vivo N-glycosylation sites. The study led to the discovery of a roster of glycoproteins with aberrant N-glycosylation levels associated with PE, including CD34, ENPP1 (ectonucleotide pyrophosphatase/phosphodiesterase family member 1), insulin-like growth factor binding protein (IGFBP3), and HYOU1 (hypoxia up-regulated 1). An emerging phenomenon that N-glycosylation is involved in several PE pathways, including cell adhesion molecules, PI3K-Akt signaling, pyrimidine metabolism, and metabolic pathways was revealed by pathway analysis of PE-associated aberrant glycoproteins. After enzymolysis, the proteins in each group were enriched with N-glycosylated peptides by lectin, the glycochain was excised by peptide N-glycosidase F (PNGase F) in H218O, and the glycosylated sites were analyzed by LC-MS/MS to achieve large-scale qualitative and quantitative analysis of N-glycosylated proteins. Our findings highlight the role of N-glycosylation in the pathogenesis of PE and provide new molecular and system-level insights for understanding and treating this disease.

Management of pregnant women who have bleeding disorders.

Bleeding disorders, including von Willebrand disease (VWD), hemophilia, other coagulation factor deficiencies, platelet disorders, defects of fibrinolysis, and connective tissue disorders, have both maternal and fetal implications. Successful management of bleeding disorders in pregnant women requires not only an understanding of bleeding disorders but also an understanding of when and how bleeding occurs in pregnancy. Bleeding does not occur during a normal pregnancy with a healthy placenta. Bleeding occurs during pregnancy when there is an interruption of the normal utero-placental interface, during miscarriage, during an ectopic pregnancy, or at the time of placental separation at the conclusion of pregnancy. Although mild platelet defects may be more prevalent, the most commonly diagnosed bleeding disorder among women is VWD. Other bleeding disorders are less common, but hemophilia carriers are unique in that they are at risk of bleeding themselves and of giving birth to an affected male infant. General guidance for maternal management of a woman who is moderately or severely affected includes obtaining coagulation factor levels at a minimum in the third trimester; planning for delivery at a center with hemostasis expertise; and anticipating the need for hemostatic agents. General guidance for fetal management includes pre-pregnancy counseling; the option of preimplantation genetic testing for hemophilia; delivery at a tertiary care center with pediatric hematology and newborn intensive care; consideration of cesarean delivery of a potentially severely affected infant; and avoidance of invasive procedures such as scalp electrodes and operative vaginal delivery in any potentially affected infant.

Atlas of fetal metabolism during mid-to-late gestation and diabetic pregnancy

Mounting evidence suggests metabolism instructs stem cell fate decisions. However, how fetal metabolism changes during development and how altered maternal metabolism shapes fetal metabolism remain unexplored. We present a descriptive atlas of invivo fetal murine metabolism during mid-to-late gestation in normal and diabetic pregnancy. Using 13C-glucose and liquid chromatography-mass spectrometry (LC-MS), we profiled the metabolism of fetal brains, hearts, livers, and placentas harvested from pregnant dams between embryonic days (E)10.5 and 18.5. Our analysis revealed metabolic features specific to a hyperglycemic environment and signatures that may denote developmental transitions during euglycemic development. We observed sorbitol accumulation in fetal tissues and altered neurotransmitter levels in fetal brains isolated from hyperglycemic dams. Tracing 13C-glucose revealed disparate fetal nutrient sourcing depending on maternal glycemic states. Regardless of glycemic state, histidine-derived metabolites accumulated in late-stage fetal tissues. Our rich dataset presents a comprehensive overview of invivo fetal tissue metabolism and alterations due to maternal hyperglycemia.

MicroRNA miR-27a as a possible regulator of anti-inflammatory macrophage phenotype in preeclamptic placenta

IntroductionThe role of the TGFβ signaling pathway, an important cascade responsible for the anti-inflammatory polarization of macrophages, in the development of both early- and late-onset preeclampsia (eoPE and loPE), remains poorly understood. In this study, we examined the components of the TGFβ signaling cascade and macrophage markers within placental tissue in normal pregnancy and in PE. MethodsPatients with eoPE, loPE, and normal pregnancy were enrolled in the study (n = 10 in each group). Following techniques were used for the investigation: immunohistochemistry analysis, western blotting, qRT-PCR, isolation of monocytes by magnetic sorting, transfection, microRNA sequencing, and bioinformatic analysis. ResultsWe observed a significant decrease in the anti-inflammatory macrophage marker CD206 in the loPE group, alongside with a significant down-regulation of CD206 protein production in both eoPE and loPE groups. The level of CD68-positive cells and relative levels of CD163 and MARCO production were comparable across the groups. However, we identified a significant decrease in the TGFβ receptor 2 production and its gene expression in the PE group. Further analysis revealed a link between TGFBR2 and MRC1 (CD206) genes through a single miRNA, hsa-miR-27a-3p. Transfecting CD14-derived macrophages with the hsa-miR-27a-3p mimic significantly changed TGFBR2 production, indicating the potential role of this miRNA in regulating the TGFβ signaling pathway. We also revealed the up-regulation of hsa-miR-27a-5p and hsa-miR-27a-3p in the trophoblast BeWo b30 cell line under the severe hypoxia condition and the fact that TGFBR2 3′ UTR could serve as a potential target for these miRNAs. DiscussionOur findings uncover a novel potential therapeutic target for managing patients with PE, significantly contributing to a deeper comprehension of the underlying mechanisms involved in the development of this pathology.

Highlighting allelic variations at the interleukin-19 locus in term of preeclampsia predisposing factors and access to an accurate diagnostic/screening option

BackgroundPreeclampsia is the main cause of preterm parturition and maternal–fetal complications. T helper 1 and T helper 2 cytokines balance is a requirement in normal pregnancy and aberrant in this immunologic balance, play an important role in the pathology of preeclampsia. In previous studies single nucleotide polymorphisms have been associated with the alteration of serum cytokine levels.ObjectiveThis study was aimed to discover association between interleukin-13 (rs20541, and rs56035208) and interleukin-19 (rs1028181 (T/C) and rs2243191(T/C)) polymorphisms with susceptibility to preeclampsia.MethodsIn this case-control study 300 women with and without preeclampsia (n = 150/each) who referred to Zeynabieh Hospital- Shiraz, Iran, from February 2021 to April 2022 were enrolled. For genotyping the interleukin-13 and interleukin-19 polymorphisms, the Allele-specific polymerase chain reaction and direct sequencing method was carried out.ResultsOur statistical results revealed no significant differences in allele and genotype frequencies for interleukin-13 polymorphisms compared to controls. We found that the interleukin‐13 polymorphisms are significantly associated with vulnerability to edema at rs20541 position and maternal drinking at rs56035208 position. But it was interesting to note that the differences of both the allele and genotype frequencies of interleukin-19 polymorphisms and their contribution to the risk of preeclampsia susceptibility were significant.ConclusionsNo risk of preeclampsia was found in all comparisons for interleukin-13 polymorphisms. However, the interleukin-19 polymorphisms were found to confer the risk of preeclampsia in our population.