Uvaol Prevents Group B Streptococcus-Induced Trophoblast Cells Inflammation and Possible Endothelial Dysfunction

Group B Streptococcus (GBS) infection during pregnancy is involved in maternal sepsis, chorioamnionitis, prematurity, fetal infection, neonatal sepsis, and neurodevelopmental alterations. The GBS-induced chorioamnionitis leads to a plethora of immune and trophoblast cells alterations that could influence endothelial cells to respond differently to angiogenic mediators and alter placental vascular structure and function in pregnant women. In this context, preventive measures are needed to reduce such dysfunctions. As such, we evaluated the effects of a non-lethal exposure to inactivated GBS on trophoblast cells and chorionic villi explants, and if the treatment with uvaol would mitigate these effects. The concentration of 106 CFU of GBS was chosen since it was unable to reduce the HTR-8/SVneo cell line nor term chorionic villi explant viability. Raman spectroscopy of trophoblast cells showed significant alterations in their biochemical signature, mostly reverted by uvaol. GBS exposure increased HTR-8/SVneo cells IL-1β and IFN-γ production, phagocytosis, oxidative stress, and decreased trophoblast cell migration. The Ea.hy926 endothelial cell line produced angiopoietin-2, CXCL-8, EGF, FGF-b, IL-6, PlGF, sPECAM-1, and VEGF in culture. When co-cultured in invasion assay with HTR-8/SVneo trophoblast cells, the co-culture had increased production of angiopoietin-2, CXCL-8, FGF-b, and VEGF, while reduced sPECAM-1 and IL-6. GBS exposure led to increased CXCL-8 and IL-6 production, both prevented by uvaol. Chorionic villi explants followed the same patterns of production when exposed to GBS and response to uvaol treatment as well. These findings demonstrate that, even a non-lethal concentration of GBS causes placental inflammation and oxidative stress, reduces trophoblast invasion of endothelial cells, and increases CXCL-8 and IL-6, key factors that participate in vascular dysregulation observed in several diseases. Furthermore, uvaol treatment prevented most of the GBS-provoked changes. Hence, uvaol could prevent the harmful effects of GBS infection for both the mother and the fetus.

Heterotopic Adipose Tissue in the Placental Parenchyma: Case Report

Objective: Reports of heterotopic tissue in the placenta are few and mainly include liver and adrenal cells. We report on adipose tissue found in the placenta. Case report: We present the case of a microscopic finding in a 25-year-old’s placenta who suffered from hypertensive disorder in pregnancy. During routine microscopic study, we observed a heterotopic, benign, circumscribed and intervillous nodule of adipose tissue. Conclusion: To our knowledge, there is no other reported case of adipocytes among chorionic villi. Why foreign tissues show up in the placenta remains unknown; however, several new theories offer explanations.

Immunohistochemical Study of Trophoblasts Cellular Regulation Processes in Chorioamnionitis and Basal Deciduitis Combined with Iron-Deficiency Anemia in Gravidas

The purpose of the study is to establish quantitative parameters of cell proliferation and apoptosis in the trophoblast of the chorionic villi in chorioamnionitis and basal deciduitis combined with iron-deficiency anemia in gravidas by means of immunohistochemical method. Materials and methods. 198 placentas were examined. The immunohistochemical procedure was performed using primary antibodies against Ki-67 and Bax antigen with imaging by a polymer system with diaminobenzidine dye. The number of Ki-67-positive nuclei of the chorionic villi trophoblast was counted, and for the Bax antigen, the optical density of the immunohistochemical staining was measured by means of microdensitometric method. Comparison of differences in mean trends was performed using the odd Student’s two-sided t-test (p≤0.05). Results and discussion. The number of Ki-67-positive trophoblast nuclei in acute chorioamnionitis with iron-deficiency anemia in gravidas was 56±3.8 ‰, and the relative units of optical density of immunohistochemical staining for protein Bax – 0.234±0.0012, in chronic – 59±3.6 ‰ and 0.2, respectively. The number of Ki-67-positive nuclei of the chorionic villi trophoblast was counted. Placentas with acute as well as chronic chorioamnionitis and basal deciduitis showed even higher averages (p <0.001). In acute basal deciduitis in anemia, the number of Ki-67-positive trophoblast nuclei was 56±3.2 ‰, the average optical density of immunohistochemical staining for protein Bax – 0.236±0.0016, in chronic – 57±3.7 and 0.249±0.0015, respectively. It should be noted that in chronic chorioamnionitis and basal deciduitis, these rates were higher than in acute. With the same regularity the average indicators of optical density of immunohistochemical staining on protein Bax in a trophoblast of chorionic villi at comorbid iron-deficiency anemia concerning an inflammation without anemia increase. We have shown that proliferative activity in iron-deficiency anemia varies with gestational age and placental prematurity, but iron-deficiency anemia in gravidas and chorionic tree maturation both individually and in combination lead to the intensification of these processes. We obtained a justification for the arithmetic mean thickness and volume of the placenta relative to observations of placenta with inflammation without anemia in this comorbid pathology. Conclusion. Iron-deficiency anemia in gravidas leads to the intensification of proliferative processes and Bax-dependent apoptosis in the trophoblast of the chorionic villi of the placenta relative to the placenta from physiological pregnancy. In acute as well as in chronic chorioamnionitis and basal deciduitis, the proliferative activity and apoptotic processes in the trophoblast of the chorionic villi of the placenta increase, while comorbid iron-deficiency anemia in gravidas intensifies only the processes of Bax-dependent apoptosis

The Contribution of QF-PCR and Pathology Studies in the Diagnosis of Diandric Triploidy/Partial Mole

Objective: the aim of our study was to assess the contribution of quantitative fluorescent polymerase chain reaction (QF-PCR) and pathology studies in the diagnosis of diandric triploidies/partial hydatidiform moles. Methods: this study included all fet al triploidies diagnosed by QF-PCR in chorionic villi or amniotic fluid in the 2 centers of BCNatal in which a maternal saliva sample was used to establish its parental origin. Pathology studies were performed in products of conception and concordance between a partial hydatidiform mole diagnosis and the finding of a diandric triploidy was assessed. Results: among 46 fetal triploidies, found in 13 ongoing pregnancies and in 33 miscarriages, there were 26 (56%) diandric triploidies. Concordant molecular (diandric triploidy) and pathology results (partial mole) were achieved in 14 cases (54%), while in 6 cases (23%) pathology studies were normal, and in the remaining 6 cases (23%) pathology studies could not be performed because miscarriage was managed medically. Conclusions: diandric triploidy is associated with partial hydatidiform mole and its diagnosis is crucial to prevent the development of persistent trophoblastic disease. QF-PCR analysis in chorionic villi or amniotic fluid provides a more accurate diagnosis of the parental origin of triploidy than the classical pathology studies.

The pathology of natural and experimentally induced Campylobacter jejuni abortion in sheep

We describe here the gross and microscopic lesions in 18 experimentally induced and 120 natural Campylobacter abortions. In natural Campylobacter abortions, gross lesions were reported infrequently; placentitis was recorded in 6% and hepatic lesions in 4% of our field cases. Placentitis was the microscopic lesion identified most consistently in natural abortions (93%) and was often observed in association with abundant bacterial colonies in chorionic villi (54%) and less often with placental vasculitis (13%). In natural abortions, suppurative fetal pneumonia (48%), necrosuppurative hepatitis (16%), and purulent meningitis (7%) were also observed. The better-preserved specimens from experimentally induced abortions were utilized to define placental changes more precisely. Placentitis was identified in all 18 experimentally induced abortions and was observed most consistently in the chorionic villus stroma (100%), often accompanied by suppurative surface exudate (89%). An inflammatory infiltrate was less commonly identified in the cotyledonary hilus (39%) and intercotyledonary placenta (22%). Bacteria were visualized in H&E-stained sections in 89% of placentas from experimentally infected ewes, primarily as well-demarcated bacterial colonies within subtrophoblastic, sinusoidal capillaries (89%), in the cotyledonary villus stroma (89%), and within the cytoplasm of trophoblasts (22%). Transmission electron microscopy and immunohistochemistry confirmed that the vast majority of the well-demarcated bacterial colonies characteristic of Campylobacter abortion were within subtrophoblastic sinusoidal capillaries. The most characteristic microscopic lesions identified in cases of Campylobacter abortion in sheep were placentitis with placental bacterial colonies, placental vasculitis, and fetal pneumonia.

Examining the Vanishing Twin Hypothesis of Neural Tube Defects: Application of an Epigenetic Predictor for Monozygotic Twinning

Strong associations between neural tube defects (NTDs) and monozygotic (MZ) twinning have long been noted, and it has been suggested that NTD cases who do not present as MZ twins may be the survivors of MZ twinning events. We have recently shown that MZ twins carry a strong, distinctive DNA methylation signature and have developed an algorithm based on genomewide DNA methylation array data that distinguishes MZ twins from dizygotic twins and other relatives at well above chance level. We have applied this algorithm to published methylation data from five fetal tissues (placental chorionic villi, kidney, spinal cord, brain and muscle) collected from spina bifida cases (n = 22), anencephalic cases (n = 15) and controls (n = 19). We see no difference in signature between cases and controls, providing no support for a common etiological role of MZ twinning in NTDs. The strong associations therefore continue to await elucidation.

RNA Demethylase FTO Mediated RNA m6A Modification Is Involved in Maintaining Maternal-Fetal Interface in Spontaneous Abortion

The N6-methyladenosine (m6A) RNA modification regulates the expression of genes associated with various biological and pathological processes, including spontaneous abortion (SA). The aim of this study was to determine the role of the m6A demethylase fat mass and obesity (FTO)- associated protein in SA. The FTO,IGF2BP1 and IGF2BP2 mRNA levels were significantly lower in the chorionic villi obtained from spontaneously aborted pregnancies compared to that of normal pregnancies, while the expression levels of METTL3 and WTAP were significantly elevated. However, ALKBH5, YTHDF2, and IGF2BP3 were elevated with no statistical significance between groups. In addition, MDA was elevated and SOD levels were decreased in the villi tissues of the SA group compared to the normal group, which was indicative of placental oxidative stress in the former. Furthermore, the expression of FTO and HLA-G were significantly decreased in the trophoblasts of the SA patients compared to that of normal pregnant women, while that of m6A was markedly higher in the former. In addition, the HLA-G and VEGFR mRNA levels were downregulated in the SA versus the control group, and that of MMP2, MMP7, MMP9 and VEGFA were upregulated. Finally, The RIP assay showed significantly decreased levels of FTO-bound HLA-G, VEGFR and MMP9 RNA in SA patients (P &lt; 0.05), which corresponded to an increase in transcripts enriched with the m6A antibody (P &lt; 0.05). However, compared with normal pregnant women, the levels of HLA-G, VEGFA, VEGFR, and MMP2 mRNA bound by YTHDF2 were significantly decreased in SA patients. Compared to the normal pregnant women, both FTO- and m6A-bound MMP7 were significantly increased in SA patients (P &lt; 0.05), but YTHDF2 almost unbound to MMP7 mRNA. In summary, the downregulation of FTO in the chorionic villi disrupts immune tolerance and angiogenesis at the maternal-fetal interface, resulting in aberrant methylation and oxidative stress that eventually leads to SA.

Differential Expression Pattern of Retroviral Envelope Gene in the Equine Placenta

Endogenous retroviruses (ERVs) are proviral phases of exogenous retroviruses, which have coevolved with vertebrate genomes for millions of years. The conservation of ERV genes throughout evolution suggests their beneficial effects on their hosts' survival. An example of such positive selection is demonstrated by the syncytin gene, which encodes a protein with affinity for various mammalian placentas that is involved in the formation of syncytiotrophoblasts. Although the horse has an epitheliochorial placenta, in which the fetal trophoblasts are simply apposed to the intact uterine epithelium, we have previously demonstrated that the equine ERV (EqERV) env RNA is unexpectedly expressed in placental tissue. In the present study, we investigated the mRNA expression pattern of the EqERV env gene in different parts of the equine placenta, to gain more insight into its putative role in the fetal–maternal relationship. To this end, we used reverse transcription–quantitative PCR (RT–qPCR) and in situ hybridization assays to analyze different target areas of the equine placenta. The retroviral env gene is expressed in the equine placenta, even though there is no syncytium or erosion of the uterine endometrium. The gene is also expressed in all the sampled areas, although with some quantitative differences. We suggest that these differences are attributable to variations in the density, height, and degree of morphological complexity of the chorionic villi forming the microcotyledons. The involvement of the EqERV env gene in different functional pathways affecting the fetus–mother relationship can be hypothesized.

Diagnostic Test On Modified Score Of Cesarean Section History In Placenta Accreta Index In Predicting Placenta Accreta Diagnosis In Rsup Dr M Djamil

Introduction : Placenta accreta is defined as abnormal implantation of placenta villi which invades myometrium without the presence of decidua bacalis resulting in placenta that is difficult to remove. Based on the depth of invasion, placenta accreta is divided into three grades, placenta accreta, placenta increta, and placenta percreta. Placenta accreta developes if chorionic villi attaches to endometrium beyond desidua basalis. Placenta increta develops when chorionic villi invades the whole myometrium. Placenta percreta developes when chorionic villi attaches beyond myometrium reaching serous and abdominal organ. Based on clinical manifestation, placenta accreta is the common term being used. Incident of abnormal placenta invasion varies from 1 : 93.000 up to 1 : 540 pregnancy. PA incidence had increased four times from 1994 to 2002 in line with increased of caesarean section procedure. Other study showed history of caesarean section increased risk of placenta accreta up to 8,7 times. Placenta accreta index (PAI) was developed based on scoring process or various parameters assessment to help diagnose placenta accreta. The parameters including: history of caesarean section ≥ 2 times, lacunae grade, sagittal smallest myometrial thickness, anterior placenta previa and birding vessel. High PAI indicates high risk of abnormal placenta invasion based on histology.Objective : This study aims to investigate modified history of cesarean section score in placenta accreta index in predicting placenta accreta diagnosis in RSUP DR M Djamil Padang.Material and methods : This was analytical study with cross sectional design. Study population was 84 placenta accreta patients in RSUP Dr. M. Djamil Padang from 2016 to 2019. Study sample was recruited using simple random sampling technique after meeting inclusion and exclusion criteria. Statistic analysis was done using Cohen’s Kappa test. Diagnostic test including sensiticivy, specivicity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy.Result : Strenght of agreement diagnosis placenta accreta based on PAI showed Kappa score of -0,002 (Kappa score < 0,2) which indicated poor strength of agreement. Strenght of agreement diagnosis placenta accreta based on modified PAI showed Kappa score of 0,353 (Kappa score range from 0,21 to 0,40) which indicated fair strength of agreement. PAI diagnostic test yield sensitivity of 97,1%, specificity of 2,8%, positive predictive value of 48,5%, negative predictive value of 50%, and accuracy of 48,6%. Modified PAI diagnostic test yield sensitivity of 97,1%, specificity of 38,9%, positive predictive value of 60%, negative predictive value of 93,3%, and accuracy of 67,1%.Conclusion : PAI has high sensitivity, low specificity, moderate positive predictive value, moderate negative predictive value, and moderate accuration. Modified PAI has high sensitivity, moderate specificity, moderate positive predictive value, high negative predictive value, and high accuracy. PAI diagnosis has poor strength of agreement compared with pathology anatomy. Modified PAI diagnosis has fair strength of agreement compared with pathology anatomy. Modified PAI has identical sensitivity with standard PAI, meanwhile for specificity, positive predictive value, negative predictive value, and accuracy, modified PAI yields higher result compared to PAI.Keywords: Modified score of history caesarean section, placenta accreta index, Modified placenta accreta index, diagnostic test of placenta accreta diagnosis