Placentas Of Women Research Articles

Значение материнского микробиома в развитии поздней задержки роста плода

The purpose — to assess the possible influence of the microbiome of the vagina, oral cavity and placenta of women on the late fetal growth retardation syndrome. Material and methods. A prospective-retrospective analysis of pregnancy and childbirth in 80 pregnant women was carried out. The main group consisted of 40 women with late fetal growth retardation syndrome, the comparison group — 40 healthy pregnant women. The study of the microbiome of the vagina, oral cavity, and placenta was carried out by sequencing of nitrogenous bases in the 16S ribosomal RNA (r-RNK) genes in 15 patients with fetal growth retardation and 8 healthy pregnant women. The Fast-DNA SPIN Kit was used to isolate the DNA material. The isolated DNA was subjected to subsequent PCR amplification followed by sequencing with forward primers and reagent kits. Results. The vaginal microbiome in women of both observation groups was characterized by the predominance of Lactobacillus, the content of which was more than 90%. The oral microbiome in both observation groups was marked by the predominance of two main bacterial types — Firmicutes and Prevotella, while Streptococcus was dominant in women with fetal growth retardation. In the placenta of women with fetal growth retardation, the bacterial diversity was significantly lower than in healthy pregnant women. The oral and placental microbiome influences the development of the late fetal growth retardation syndrome. Conclusion. The influence of the altered maternal microbiome on the formation of late fetal growth retardation is not excluded.

Evidence of maternal vascular malperfusion in placentas of women with congenital heart disease.

• Women with congenital heart disease (CHD) deliver small babies and placentas. • Maternal CHD was associated with a high prevalence of pre-eclampsia. • Their placentas have evidence of maternal vascular malperfusion and no vasculopathy. • Cardiovascular dysfunction due to CHD may impact placental development and consequently fetal growth.

Overexpression of glycolysis markers in placental tissue of pregnant women with chronic venous disease: a histological study.

Chronic Venous Disease (CVD) refers to a wide variety of venous disorders being the varicose veins its most common manifestation. It is well-established the link between pregnancy and the risk of suffering CVD, due to hormonal or haematological factors, especially during the third trimester. In the same manner, previous studies have demonstrated the detrimental effect of this condition in the placental tissue of pregnant women, including in the normal physiology and the metabolomic profile of this organ. In this context, the aim of this study was to evaluate the glucose homeostasis in the placental tissue of women presenting CVD. Through immunohistochemistry, we studied the protein expression of the glucose transporter 1 (GLUT-1), Phosphoglycerate kinase 1 (PGK1), aldolase (ALD), Glyceraldehyde-3-phosphate dehydrogenase (GA3PDH) and lactate dehydrogenase (LDH). Our results have reported a significative increase in the expression of GLUT-1, PGK1, ALD, GA3PDH and the isoenzyme LDHA in placentas of women with CVD. This work has proven for the first-time an altered glucose metabolism in the placental tissue of women affected by CVD, what may aid to understand the pathophysiological mechanisms of this condition in more distant organs such as placenta. Furthermore, our research also supports the basis for further studies in the metabolic phenotyping of the human placenta due to CVD, which may be considered during the late pregnancy in these women.

Molecular detection of Toxoplasma gondii in placentas of women who received therapy during gestation in a toxoplasmosis outbreak.

Toxoplasmosis is a disease caused by T. gondii, a protozoa which affects humans and animals and is widely distributed worldwide. In humans, there is great concern due to the serious consequences that can occur in the infection of pregnant women and the newborn. The early diagnosis of gestational toxoplasmosis is important for treatment to be carried out in order to prevent vertical transmission or reduce damage. The diagnosis can be made through the detection of antibodies in pregnant women or neonates and PCR of amniotic fluid. Previous studies have also reported PCR of the placenta as a good diagnostic test. Our study evaluated the detection of T. gondii DNA in placenta samples from parturients seen at the University Hospital of Santa Maria, Southern Brazil and treated during the pregnancy. We performed PCR in forty samples and five were positive, representing 12.5%. When correlating the treatment time and the detection of DNA in the placentas, no significant result was found. The prevalence of positive samples was lower than in other studies in the literature. The data reaffirm the importance of carrying out the analysis of the placenta.

Some opportunistic infections in the structure of premature birth causes

Aim. To determine the structure and detection rate of some opportunistic infections in premature birth.Materials and methods. The study was carried out at the premises of the Research Institute of Maternity and Childhood Protection and the Pathology Department of the Khabarovsk Perinatal Center. We studied 62 placentas from women whose pregnancy ended prematurely and placentas and organ samples (heart, lungs, liver, and kidneys) from 14 premature infants who died in the early neonatal period. Thirty placentas of women who delivered full-term live babies were classified as a control group. Genomes of Chlamydia trachomatis, Mycoplasma hominis, Mycoplasma genitalium, Ureaplasma species (Ureaplasma urealyticum + Ureaplasma parvum), Cytomegalovirus, Herpes simplex virus, Human herpesvirus 4 type, Human herpesvirus 6 type, Parvovirus B19, Listeria monocytogenes, Streptococcus agalactiae, Streptococcus species, Streptococcus pyogenes, Haemophilus influenza, Klebsiella pneumoniae, Candida albicans were detected by polymerase chain reaction (PCR) in samples of placental tissue and samples of internal organs of deceased newborns. Results. The rate of opportunistic agent detection in the placentas from women with preterm birth made 59.6% and in the sectional material from premature newborns who died in the early neonatal period (78.6%), which figures exceeded the same indicator in the control group (30.0%) respectively, by 2.0 (p=0.007) and 2.6 (p=0.002), respectively. In 47.9±7.2% of cases of all positive results, the material from women with preterm birth presented with various combinations of two, three, and four infectious agents, having common pathogenic links, which contributes to the aggravation of pathogenic processes, comorbidity or multimorbidity. According to the detection rates, in terms of total monoinfections and mixed infection components, pathogens detected during preterm birth were distributed as follows: U. urealyticum ‒ 34,2±5,4%; S. agalactiae ‒ 17,1±4,3%; M. hominis ‒ 15,8±4,1%; S. species (S. sanguis, S. salivarius, S. mitis, S. mutans) ‒ 13,1±3,8%; Cytomegalovirus ‒ 11,8±3,7%; Human herpesvirus 4 type – 9,2±3,3%; M. genitalium ‒ 2,6±1,8%. Conclusion. PCR testing showed that placentas from women whose pregnancy ended prematurely and samples of placenta and organs of premature infants who died in the early neonatal period presented with opportunistic agents colonizing female genital tract (streptococci, mycoplasmas) or ubiquitous herpesviruses persistent and reproduced in human lymphocytes (Cytomegalovirus, Human herpesvirus 4 type). Associations of microorganisms that cause comorbidity or multimorbidity account for a significant portion of the infectious agents detected. The context for a microbiota-integrated opportunistic agent to transform into a pathogenic strain, identification of transformation predictors, and possible tools to correct the disorders – all these require further research.

Features of the morphological structure of the placenta in pregnant women with preeclampsia

To study morphological features of the placenta in women in labor, pregnancy which complicated by preeclampsia we studied 26 placentae, of which 17 were from pregnant women with mild to moderate preeclampsia (basic group) and 9 from healthy women (control group). Histologically the study was conducted with methodically recommendations of T.D. Zadorozhnaya et al. for light microscopy.
 During the study of morphological features of the placenta in women in labor with preeclampsia were installed morphological changes in the placenta, which reflect a tendency to develop compensatory-adaptive reactions following their stress and exhaustion, which is a sign of placental insufficiency. Received data allow claiming a high frequency of development placental insufficiency in pregnant women with risk factors such as chronic salpingo-oophoritis, anemia, late preeclampsia, and inflammation diseases kidney.

Upregulated pigment epithelium-derived factor (PEDF) promotes trophoblast apoptosis and inhibits invasion in preeclampsia

Preeclampsia (PE) is a severe pregnancy-specific disorder. Previous findings indicated that pigment epithelium-derived factor (PEDF) was upregulated in placentas of women with PE. Here, we investigated the role of PEDF in trophoblast function, especially under hypoxia. The effects of hypoxia on the morphology of extravillous trophoblast (EVT)-derived HTR-8Svneo cells were observed under inverted microscope. Transfections with Lipofectamine LTX were performed according to the manufacturer's protocol. The expression of PEDF protein and mRNA were confirmed by immunofluorescence (IF) and quantitative real-time PCR (qPCR). Apoptosis was detected by transferase-mediated dUTP nick end labeling (TUNEL) assay, and proliferation of trophoblast was detected by CCK-8 method. The invasion capacity of trophoblast was assessed by Transwell assay. PEDF was expressed in HTR-8/SVneo under both normoxia and hypoxic stress. However, cells of hypoxia groups had higher expression level of PEDF, increased apoptosis and decreased invasion capability, as compared with normoxia group. Moreover, after transfection with plasmid expressing PEDF gene, overexpression of PEDF modulated trophoblast activities. In addition, PEDF expression was negatively associated with invasion while positively correlated with apoptosis.Our data suggest that PEDF is an important factor to maintain the biological function of trophoblast cells, thus representing a rational therapeutic target in PE.

PECULIARITIES OF PREGNANCY COURSE, CHILDBIRTH, AND MORPHOFUNCTIONAL STATE OF PLACENTA IN WOMEN WITH INTRAUTERINE FETAL GROWTH RETARDATION

Fetal growth retardation is a severe obstetric pathology that is accompanied by significant reproductive losses and the cost of treating newborns. The aim of the study is to investigate the clinical difference between the course of pregnancy, childbirth, and morphofunctional state of the placenta in women who gave birth to children with low birth weight before gestational age and normal anthropometric parameters. Materials and methods. The study included 37 women; the individuals of the main group gave birth to a child with low birth weight before gestational age (n = 25), the comparison group consisted of women who had uneventful pregnancy and children born with normal anthropometric parameters (n = 12) . Results and discussion. Pregnancy and childbirth in the main group were registered mostly within the age range of 30 and 39, burdened with bad habits, accompanied by somatic and obstetric pathology. The predominant mode of preterm delivery in most of the main group was cesarean section caused by fetal distress in contrast to women in the comparison group. Analysis of the morphofunctional state of the placenta from the women in the main groups revealed both general structural-adaptive and structural-morphological changes that indicated compensatory hyperplasia of placental tissue in women with foetal intrauterine growth retardation that is characteristic of the compensated stage of chronic placental insufficiency. Conclusion. The multicomponent impact of various factors may contribute to an increased risk of fetal growth retardation and its progression, so timely correction of risk factors will help to improve the management of pregnancy and perinatal outcomes.

Inflammatory changes in the placenta in ischemic-cervical insufficiency

Introduction.The high frequency of inflammatory changin the placenta in isthmic-cervical insufficiency may be primarily associated with an ascending infection as a result of a violation of the barrier function of the cervix, however, premature remodeling of the cervix may also be secondary due to an already existing process. The study of the features of the spread of the infectious process and thnature of the inflammatory reaction in various structures of the placenta and fetal membranes can contribute to the understanding of pathogenetic mechanisms of preterm birth in isthmic-crvical insufficiency.Aim of the study— to evaluate the frequency and structure of inflammatory changes in the placenta in women with isthmic-cervical insufficiency.Materials and methods.A prospective cohort study was conduct, which included 154 pregnant women taken by the continuous sampling method. All patients were divided into two groups: group 1 consisted of 100 pregnant women with isthmic-cervical insufficiency, group 2 — pregnant women without isthmic-cervical insufficiency. All women after childbirth underwent a pathomorphological examination of the afterbirth.Results and discussion.In women with isthmic-cervical insufficiency, inflamatory changes in the placenta were detected in 71% (71) of cases, which was significantly more frequent compared to group 2 — 38.9% (21). Membranitis was significantly more frequent in isthmic-cervical insufficiency, amounting to 16% (16) versus 3.7% (2) comparison group (OR=4.32, 95% СI=1.03-18.09, p=0.023). Chorioamnionitis was 6 times more common in the afterbirth in women of group 1, accounting for 12% (12), versus 1.9% (1) in group 2 (OR=6.48, 95% CI=0.87-48.51, p=0.031). Involvement of the umbilical cord in the inflammatory process occurred only in pregnant women with isthmic-cervical insufficiency: funiculitis was combined with membranitis in 4% (4) of cases (p=0.137), the combination of funiculitis with choriomnionitis was detcted in 7% (7) of women p=0.047).Conclusion.The frequencof detection of inflammatory changes in the placenta in ICN was 71% (71). In the structure of inflammatory changes of the afterbirth in patients with ICN, the defeat of the fetal membranes prevails, which may indicate a predominatly ascending path of infection in this pathology. Damage membranes prevails, which may indicate a predominatly ascending path of infection in this pathology. Damage to the umbilical cord in ICN can occur both wth total inflammation of all structures of the placenta, and directly through the fetal membranes, without involving the chorion in the process.

SARS-CoV-2 Infection in Pregnancy: Clinical Signs, Placental Pathology, and Neonatal Outcome-Implications for Clinical Care.

Introduction: The current COVID-19 pandemic has been associated with high rates of mortality and significant morbidity. Both the risk of infection for pregnant women and the risk of vertical transmission have been evaluated, and the presence of the SARS-CoV-2 virus has been demonstrated both in the placenta and in the amniochorionic membranes. However, the actual effects of this pathogen on pregnancy and on placental morphology are still unclear.Objective: To describe histopathologic findings in the placentas of women with SARS-CoV-2 infection during pregnancy and their correlation with clinical signs and perinatal outcome.Methods: Placental tissues from pregnant women with SARS-CoV-2 infection delivering between March 2020 and February 2021 were analyzed.Results: One hundred six placentas from women with SARS-CoV-2 infection during pregnancy who delivered in Fondazione Policlinico A. Gemelli were examined. Most of them were asymptomatic. All neonates had available test results for SARS-CoV-2 and only one resulted positive. Placental tissues mainly showed signs of maternal vascular malperfusion and of placenta injury in terms of syncytial node increase (96.2%), villar agglutination (77.3%), neointimal hyperplasia (76.4%), excessive fibrin deposition (43.3%), and chorangiosis (35.8%). No significant differences in the frequency of the histopathological lesions were observed according to maternal symptoms.Conclusion: Looking to placental tissues from SARS-CoV-2 positive women at the screening performed close to delivery, placental injuries could be detected without any correlation with fetal and neonatal outcomes. We hypothesize that short latency between SARS-CoV-2 infection and delivery is the main reason for these observations.

Altered protein O-GlcNAcylation in placentas from mothers with diabetes causes aberrant endocytosis in placental trophoblast cells

Women with pre-existing diabetes have an increased risk of poor pregnancy outcomes, including disordered fetal growth, caused by changes to placental function. Here we investigate the possibility that the hexosamine biosynthetic pathway, which utilises cellular nutrients to regulate protein function via post-translationally modification with O-linked N-acetylglucosamine (GlcNAc), mediates the placental response to the maternal metabolic milieu. Mass spectrometry analysis revealed that the placental O-GlcNAcome is altered in women with type 1 (n = 6) or type 2 (n = 6) diabetes T2D (≥ twofold change in abundance in 162 and 165 GlcNAcylated proteins respectively compared to BMI-matched controls n = 11). Ingenuity pathway analysis indicated changes to clathrin-mediated endocytosis (CME) and CME-associated proteins, clathrin, Transferrin (TF), TF receptor and multiple Rabs, were identified as O-GlcNAcylation targets. Stimulating protein O-GlcNAcylation using glucosamine (2.5 mM) increased the rate of TF endocytosis by human placental cells (p = 0.02) and explants (p = 0.04). Differential GlcNAcylation of CME proteins suggests altered transfer of cargo by placentas of women with pre-gestational diabetes, which may contribute to alterations in fetal growth. The human placental O-GlcNAcome provides a resource to aid further investigation of molecular mechanisms governing placental nutrient sensing.

VP31.08: Placental profiling in women with confirmed COVID‐19 infection

to profile the typical lesion characteristics found in placentas of women with COVID-19. Consecutive placental specimens were acquired from pregnant women with confirmed COVID-19 infection by RT-PCR delivering between May 2019 – June 2021 in a tertiary reference hospital. Histological analysis of the placenta was carried out by the same pathologist in all cases and categorised according to the Amsterdam classification for histopathology analysis of the placenta. A principal component analysis was performed to assess the typical placental profile in women with COVID-19 infection. A total of 351 positive-COVID-19 consecutive placentas were analysed. Three main COVID-19 placental profiles were found after principal component analysis. The first profile comprised maternal venous malperfusion, deciduitis, thrombosis, and atherosis with absence of chorioamnionitis, explaining 16% of all placentas. The second placental profile was made of fetal venous malperfusion, placental chorangiosis, thrombosis with absence of atherosis and fibrinoid necrosis explaining 13% of all observations. The third profile comprised placental villitis, thrombosis, and fibrinoid necrosis with absence of fetal venous malperfusion, and deciduitis, explaining 12% of all observations. The most common COVID-19 placental lesion profile comprises maternal venous malperfusion, deciduitis, thrombosis, and atherosis followed by fetal venous malperfusion, placental chorangiosis, and thrombosis. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Maternal-neonatal transfer of SARS-CoV-2 immunoglobulin G antibodies among parturient women treated with BNT162b2 messenger RNA vaccine during pregnancy

BACKGROUNDThe exclusion of pregnant women from initial COVID-19 messenger RNA vaccine trials raised hesitancy regarding the benefits of vaccination for pregnant women, hence little is known about vaccines’ efficacy in this population.OBJECTIVETo determine the maternal-neonatal transplacental transfer of SARS-CoV-2 antibodies among vaccinated parturient women. A control group of COVID-19-recovered patients was included to compare the immunoglobulin G levels between vaccinated and recovered patients.STUDY DESIGNThis is a prospective cohort study conducted in a single tertiary medical center in Israel between February and March 2021; parturient women vaccinated with the BNT162b2 messenger RNA vaccine during pregnancy were included and compared with COVID-19-recovered parturient women. SARS-CoV-2 immunoglobulin G antibodies were measured in maternal and cord sera, dried blood spot samples taken from newborns, and breast milk samples. The primary aim was to determine whether neonatal cord and dried blood spot samples were positive for SARS-CoV-2 antibodies and to evaluate the transfer ratio, defined as cord blood immunoglobulin G divided by maternal immunoglobulin G levels.RESULTSThe study included 64 vaccinated parturient women and 11 parturient women who had COVID-19 during pregnancy. All maternal blood sera samples and 98.3% of the cord blood sera samples were positive for SARS-Cov-2 immunoglobulin G with median concentrations of 26.1 (interquartile range, 22.0–39.7) and 20.2 (interquartile range, 12.7–29.0), respectively. Similarly, 96.4% of neonatal blood spot samples and all breast milk samples were positive for SARS-CoV-2 immunoglobulin G with median concentrations of 11.0 (interquartile range, 7.2–12.8) and 4.9 (interquartile range, 3.8–6.0), respectively. There was a significant positive correlation between maternal serum levels of SARS-CoV-2 immunoglobulin G and cord blood (r=0.483; P=.0001), neonatal blood spot (r=0.515; P=.004), and breast milk levels (r=0.396; P=.005) of SARS-CoV-2 immunoglobulin G. The median placental transfer ratio of SARS-COV-2 immunoglobulin G was 0.77. Comparison of vaccinated and recovered COVID-19 patients revealed significantly higher SARS-CoV-2 immunoglobulin G levels in maternal serum and cord blood among vaccinated women (P<.0001).CONCLUSIONOur study demonstrated the efficient transfer of SARS-CoV-2 immunoglobulin G across the placenta in women, vaccinated with the BNT162b2 messenger RNA vaccine during pregnancy, to their neonates, with a positive correlation between maternal serum and cord blood antibody concentrations. In addition to maternal protection against COVID-19, the vaccine may also provide neonatal humoral immunity.

Autophagy Activation by Hypoxia Regulates Angiogenesis and Apoptosis in Oxidized Low-Density Lipoprotein-Induced Preeclampsia.

Objective: Autophagy influences a wide range of physiological and pathological processes in the human body. In this study, we aimed to investigate the role of autophagy in early-onset preeclampsia (EOPE); autophagy activation by hypoxia could rescue impaired angiogenesis and apoptosis in preeclampsia, leading by ox-LDL.Methods: Transmission electron microscopy was applied to identify autolysosomes in trophoblast cells of the placenta apical region. Quantitative real-time polymerase chain reaction, Western blot, flow cytometry, and wound-healing assays were adopted to determine autophagy activity, angiogenesis, and apoptosis in placenta tissues or HTR8/SVneo cells.Results: Autophagy activity was inhibited in the placenta of women who experienced EOPE; autophagy activation by hypoxia enhanced the migration ability, rescued ox-LDL–mediated impaired angiogenesis in HTR8/SVneo cells [vascular endothelial growth factor A (VEGFA) downregulation and FMS-like tyrosine kinase-1 (FLT1) upregulation], and protected against cell apoptosis (BAX downregulation).Conclusion: Autophagy could maintain the function of trophoblast cells by differentially regulating the expression of VEGFA and FLT1 and protecting against cell apoptosis at the maternal–fetal interface, potentially related to prevention of preeclampsia.

English

BACKGROUND The coronavirus disease 2019 (Covid-19), caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), is a global public health emergency. Data on the effect of coronavirus disease 2019 in pregnancy is limited to few case series. The purpose of this study was to describe the histopathological findings in the placentas of women with Covid-19 during pregnancy. METHODS Pregnant women with Covid-19 who delivered between August 1, 2020 and May 10, 2021, at Government Medical College, Trivandrum were considered for the study. Handling of specimens were carried out using Indian council of medical research (ICMR) guidelines for Covid-19 specimens. Placentas underwent routine clinical examination and processing. Clinical information was retrieved from the medical records. Histological examination was performed and features classified into maternal vascular malperfusion (MVM) and fetal vascular malperfusion (FVM). RESULTS 50 placentas from patients with severe acute respiratory syndrome coronavirus 2 were examined [33 patients delivered at term, 12 patients were preterm, 4 cases were intrauterine fetal demise and 1 case was medical termination of pregnancy (MTP)]. Patients with risk factors for maternal and fetal vascular malperfusion were excluded. 8 cases showed features of maternal vascular malperfusion and 11 cases showed features of fetal vascular malperfusion. Among intra uterine fetal death (IUFD) cases, 2 cases showed features of vascular malperfusion, 7 cases showed low grade acute inflammatory pathology which needs further studies with a greater number of cases to establish relationship with Covid-19 virus. CONCLUSIONS Covid-19 placentas showed increased rates of maternal and fetal vascular malperfusion. These changes may reflect a hypercoagulable state influencing placental pathology and hence an increased antenatal surveillance for women diagnosed with SARS–CoV-2 infection may be warranted. Further studies with control groups are necessary to determine the reproducibility and significance of these initial findings. KEYWORDS Covid-19, Pregnancy, Maternal Vascular Malperfusion, Fetal Vascular Malperfusion.

Pathomorphological changes of the placenta in coronavirus disease (COVID 19)

The aim of this research was to study the pathomorphological changes in the placenta in case of coronavirus disease (COVID-19) in the anamnesis during different periods of gestation. Materials and methods. 53 placentas of women with the coronavirus disease (COVID-19) (RNA determination of the SARS-CoV-2) during the pregnancy were studied. The material was divided into the following groups: 1 and 2 – placentas in cases with a negative PCR test in full-term newborns who were born in satisfactory condition and high Apgar score. Group 1 (n = 29) – mother’s history of COVID-19 at 34–39 weeks of gestation; group 2 (n = 17) – mother’s history of COVID-19 at 23-33 weeks of gestation; 3 (n = 7) – placenta in case of antenatal fetal death. Results. Statistically significant differences were revealed between study groups: chorioamnionitis prevailed in group 1 (in 28 cases (96.6 %); confidence interval (CI): 86.4–100.0 %; P1-2 = 0.004); in groups 2 and 3 – arteriosclerosis (in 13 cases (76.5 %); CI: 52.2– 93.9 %; P1-2 = 0.0003 and in 7 cases (100 %); CI: 75.7–100.0 %; P1-3 = 0.001; respectively). COVID-19 was diagnosed in group 1 from 34 to 39 weeks of gestation (median 36.5), group 2 from 23 to 33 weeks (median 28.0), in group 3 from 13 to 32 weeks with a median of 24.5. Antenatal fetal death was observed between 14 and 41 weeks (median 31.4). Conclusions. Pathomorphological changes in the placenta in the coronavirus disease COVID-19 depended on the duration of the post-COVID interval (the time interval from the diagnosis of COVID-19 and the moment of delivery), due to the sequential change in the phases of the inflammatory process: alteration, exudation and proliferation, followed by fibrosis. The formation of acute placental insufficiency in coronavirus disease COVID-19, diagnosed up to 1–6 weeks to delivery, is associated with the development of severe disorders of circulation and acute exudative inflammatory reactions of varying severity. The formation of chronic placental insufficiency is associated with the proliferative stage of inflammation. These changes lead to the development of fibrosis in the wall of arterioles and intervillous space. The most significant structural changes in the placenta, leading to placental insufficiency, were observed in group 2 – at the time of infection in the period from 23–33 weeks of pregnancy. Coronavirus disease COVID-19 in the mother in the second trimester of pregnancy is a risk factor for perinatal losses, which are caused by the changes in the placenta described above with an increase in the duration of the post-COVID interval.

ADCY5, CAPN10 and JAZF1 Gene Polymorphisms and Placental Expression in Women with Gestational Diabetes

Gestational diabetes mellitus (GDM) is carbohydrate intolerance that occurs during pregnancy. This disease may lead to various maternal and neonatal complications; therefore, early diagnosis is very important. Because of the similarity in pathogenesis of type 2 diabetes and GDM, the genetic variants associated with type 2 diabetes are commonly investigated in GDM. The aim of the present study was to examine the associations between the polymorphisms in the ADCY5 (rs11708067, rs2877716), CAPN10 (rs2975760, rs3792267), and JAZF1 (rs864745) genes and GDM as well as to determine the expression of these genes in the placenta. This study included 272 pregnant women with GDM and 348 pregnant women with normal glucose tolerance. The diagnosis of GDM was based on a 75 g oral glucose tolerance test (OGTT) at 24–28 weeks gestation, according to International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria. There were no statistically significant differences in the distribution of the ADCY5 gene (rs11708067, rs2877716) and CAPN10 gene (rs2975760, rs3792267) polymorphisms between pregnant women with normal carbohydrate tolerance and pregnant women with GDM. We have shown a lower frequency of JAZF1 gene rs864745 C allele carriers among women with GDM CC + CT vs. TT (OR = 0.60, 95% CI = 0.41–0.87, p = 0.006), and C vs. T (OR = 0.75, 95% CI = 0.60–0.95, p = 0.014). In addition, ADCY5 and JAZF1 gene expression was statistically significantly increased in the placentas of women with GDM compared with that of healthy women. The expression of the CAPN10 gene did not differ significantly between women with and without GDM. Our results indicate increased expression of JAZF1 and ADCY5 genes in the placentas of women with GDM as well as a protective effect of the C allele of the JAZF1 rs864745 gene polymorphism on the development of GDM in pregnant women.

The Choline Metabolite TMAO Inhibits NETosis and Promotes Placental Development in GDM of Humans and Mice.

Choline metabolite trimethylamine N-oxide (TMAO) has been recognized as a risk factor of gestational diabetes mellitus (GDM), but its exact role in GDM has not been reported. In this study, we focused on the placenta development to reveal the role of TMAO in GDM. We found that the TMAO levels in peripheral and cord plasma were increased in women with GDM and that TMAO levels were positively correlated with newborn weight and placental thickness. Neutrophil extracellular traps (NETs) in the peripheral and cord plasma and the myeloperoxidase expression in the placenta of women with GDM also increased. NETs could inhibit the proliferation, migration, invasion, and angiogenesis of HTR-8/Svneo cells. However, TMAO not only could inhibit the formation of NETs but also could enhance the biological function of HTR-8/Svneo cells. With induction of GDM in NETs-deficient PAD4-/- and wild-type mice, the placental weight of PAD4-/- mice increased significantly. TMAO feeding also inhibited the formation of NETs and further increased the weight of the placenta and fetuses, and this increase did not affect the placental structure. Our data indicate that higher TMAO levels and the formation of abnormal NETs were associated with GDM. TMAO not only could promote the development of the placenta and fetuses but also could inhibit the formation of NETs.

Assessment of Placental Extracellular Vesicles-Associated Fas Ligand and TNF-Related Apoptosis-Inducing Ligand in Pregnancies Complicated by Early and Late Onset Preeclampsia.

Preeclampsia (PE) is a hypertensive disorder that affects 2–8% of pregnancies and is one of the main causes of fetal, neonatal, and maternal mortality and morbidity worldwide. Although PE etiology and pathophysiology remain unknown, there is evidence that the hyperactivation of maternal immunity cells against placental cells triggers trophoblast cell apoptosis and death. It has also been reported that placenta-derived extracellular vesicles (EV) carry Fas ligand (FasL) and Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and trigger apoptosis in Jurkat T cells. This study aimed to quantify and compare FasL and TRAIL expression in EV derived from cultures of placenta explants from women with PE (early versus late) and women with uncomplicated pregnancies. Also, the study assessed EV capacity to induce apoptosis in Jurkat T cells. The authors isolated EV from placenta explant cultures, quantified FasL and TRAIL using ELISA, and analyzed EV apoptosis-inducing capability by flow cytometry. Results showed increased FasL and TRAIL in EV derived from placenta of women with PE, and increased EV apoptosis-inducing capability in Jurkat T cells. These results offer supporting evidence that EV FasL and TRAIL play a role in the pathophysiology of PE.

WISP1 is increased in the maternal serum, adipose tissue, and placenta of women with gestational diabetes mellitus

WISP1 is increased in the maternal serum, adipose tissue, and placenta of women with gestational diabetes mellitus