Trimester Of Normal Pregnancy Research Articles

PB1536 Plasmin Generation and Its Determinants in the Third Trimester of Normal Pregnancy

PB1536 Plasmin Generation and Its Determinants in the Third Trimester of Normal Pregnancy

Comparison of oxidative stress levels during the third Trimester in normal pregnancy and preeclampsia.

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. 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 ischemiamodified 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 pvalue of ≤0.05 was considered significant. Comparison of ischemia-modified albumin and malondialdehyde values between group I and group 2 showed a highly significant difference of pvalue of <0.001. 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.

Correlation of Sonographic Gestational Age with Fetal Kidney Length in Normal Pregnancy

Precise evaluation of gestational age is essential for quality maternity care. Ultrasonography is the most readily available and reliable method to establish gestational age. This study aims to use the length of the fetal kidney as a reliable parameter to measure gestational age in late second and third trimesters. Objective: To determine the relationship between fetal kidney length and gestational age in weeks during the late 2nd and 3rd trimester of normal pregnancy. Methods: It was a prospective cross-sectional study conducted on 105 singleton normal pregnant females between 24th and 40th weeks of gestation who came to the obstetrics and gynecology department at a private sector hospital in Kharian, Pakistan. The duration of the study was four months. Bi-parietal diameter, femur length, and fetal kidney lengths were measured. Statistical analyses were applied using SPSS version 22.0. Results: A moderately significant positive correlation was identified between different gestational age measuring parameters and fetal kidney length. The correlation was significant at the level of 0.01. The correlational values of GA according to LMP with FKLL and FKLR were (r= .85**) and (r= .87**) respectively. GA with BPD indicates a moderately significant positive correlation with FKLL and FKLR (r= .94**) and (r=.94**). GA with FL also shows a moderately significant positive correlation with FKLL and FKLR (r= .83**) and (r= .83**), respectively. Conclusion: In conclusion, fetal kidney length in millimeters correlates well with gestational age in weeks and shows linear growth with gestational age throughout pregnancy. Gestational age estimated from fetal kidney length gives improved dating of fetal age

Measurement of Amniotic Fluid Volume in 2nd and 3rd Trimesters of Normal Pregnancies

The important implication of obstetric care is the assessment of amniotic fluid volume. This assessment can prevent anomalies that are associated with oligohydramnios and polyhydramnios. Objective: To evaluate normal amniotic fluid volume in the 2nd and 3rd trimesters with the correlation of gestational age. Methods: It was a cross-sectional study and data were collected from a private health care setup in Gujrat, Pakistan. After informed consent data were collected in four months. A sample size of 75 patients was calculated conveniently using a mean from previous related studies. The women with singleton gestation from 20 to 40 years of age group were included in this research. The data were entered and analyzed on SPSS version 20. Results: This study showed that 47(62.7%) of women were multigravida and 28(37.3%) were primigravida. The most frequent maternal age group was 26-30(38.7%) years and the gestational age group was 31 to 35(42.7%) weeks. At the gestational age of 21-25 weeks, the mean of AFI was 14.38 and the mean of SDP was 5.69, while at the age of 26-30 weeks the estimated mean of AFI was 12.12 and the mean of SDP was 5.11. The mean of AFI and SDP at the age of 31-35 weeks were calculated at 11.48 and 4.26 respectively. At the age of 36-40 weeks, the estimated mean of AFI and SDP were calculated 10.22 and 3.73 correspondingly. Conclusions: This study concluded that amniotic fluid volume measured by amniotic fluid index and the single deep pool was increased in the 2nd trimester from 21-25 weeks of gestation and then progressively reduced in the third trimester as the pregnancy advances.

Dynamic changes in regulatory T cells during normal pregnancy, recurrent pregnancy loss, and gestational diabetes

Regulatory T cells (Tregs) are critical to regulating maternal T-cell activation against trophoblast; however, the characteristics of maternal Tregs during pregnancy have not been elucidated well. In this study, we analyzed the proportion of CD4+ and CD8+ Tregs in the peripheral blood and their surface expression of PD-1, GITR, HLA-G, and CTLA-4 in normal pregnant women during the first (n = 28), second (n = 43), and the third trimester (n = 33), non-pregnant women (n = 57), pregnant women with a history of recurrent pregnancy loss (RPL) during the first trimester (n = 21), and pregnant women with gestational diabetes mellitus (GDM) during the second (n = 17) and third trimester (n = 28). The proportions of CD4+ and CD8+ Tregs were higher in normal pregnant women than that of non-pregnant women (P < 0.01 respectively). The proportion of CD4+ Tregs was peaked during the second trimester and then decreased. Contrarily, the proportion of CD8+ Tregs was increased throughout gestation and peaked during the third trimester. Proportions of CD4+/PD-1+ Tregs, CD4+/GITR+ Tregs, CD8+/PD-1+ Tregs, and CD8+/CTLA-4+ Tregs peak during the third trimester of normal pregnancy. Pregnant women with RPL and GDM had lower proportions of CD4+ Tregs (P < 0.05 and P < 0.01 respectively) and higher proportions of CD8+ Tregs (P < 0.01 and P < 0.01 respectively) than those of normal pregnancies.Together, our findings indicate that CD4+ and CD8+ Tregs play different roles in pregnancy maintenance, and the dysregulation may contribute to obstetrical complications.

The Regulatory Network Played by miRNAs During Normal Pregnancy and Preeclampsia: A Comparative Study.

Preeclampsia is a pregnancy-specific syndrome, characterized by hypertension, proteinuria, and edema. Affecting between 2% and 8% of gestations worldwide, it accounts for 10% to 15% of maternal deaths. Although its etiology remains unclear, it includes complex pathological processes involving microRNAs, small non-coding RNA molecules with post-transcriptional repression effects on target mRNAs. To assess the expression of miRNAs during normal pregnancies and those complicated by preeclampsia, a sample of Venezuelan women were studied. Nine placental microRNAs (hsa-miR- 20a-5p, 21-3p, 26a-5p, 181a-5p, 199a-5p, 210-3p, 222-5p, 223-3p, 424-3p) were measured in maternal plasma during the second and third trimesters of normal pregnancies, using a SYBR Green®-based real-time PCR, and compared the results against women affected by preeclampsia. All assessed miRNAs were detected in maternal plasma in pregnancies with and without preeclampsia. All except miR-222 were over-expressed during disease when compared to the second and to third-trimester controls. miR-20a, miR-21, miR-26a, and miR-223 were down-regulated in the third trimester in comparison to the second trimester in normal pregnancies. The variation of the miRNAs expression through normal pregnancies suggested their involvement in normal physiological pregnancy processes. In contrast, the significant deregulation of the nine studied miRNAs during preeclampsia indicated the involvement of their target genes in the pathogenesis of the disease. miR-199a and miR-21-3p showed the greatest changes in expression. This study shows for the first time the presence of miR-20a, miR-199, and miR-424 and the variations they undergo in the plasma of pregnant women with preeclampsia.

Coordinated Expressional Landscape of the Human Placental miRNome and Transcriptome.

Placenta is a unique organ that serves its own function, and contributes to maternal gestational adaptation and fetal development. Coordination of its transcriptome to satisfy all the maternal-fetal needs across gestation is not fully understood. MicroRNAs are powerful transcriptome modulators capable to adjust rapidly the expression level and dynamics of large gene sets. This MiR-Seq based study presents a multi-omics investigation of the human placental miRNome and its synergy with the transcriptome. The analysis included 52 placentas representing three trimesters of normal pregnancy, and term cases of late-onset preeclampsia (LO-PE), gestational diabetes and affected fetal growth. Gestational-age dependent differential expression (FDR < 0.05) was detected for 319 of 417 tested miRNAs (76.5%). A shared list of target genes of dynamic miRNAs suggested their coordinated action. The most abundant miR-143-3p revealed as a marker for pregnancy progression. The data suggested critical, but distinct roles of placenta-specific imprinted C19MC and C14MC miRNA clusters. Paternally encoded primate-specific C19MC was highly transcribed during first trimester, potentially fine-tuning the early placental transcriptome in dosage-sensitive manner. Maternally encoded eutherian C14MC showed high expression until term, underlining its key contribution across gestation. A major shift in placental miRNome (16% miRNAs) was observed in LO-PE, but not in other term pregnancy complications. Notably, 13/38 upregulated miRNAs were transcribed from C19MC and only one from C14MC, whereas 11/28 downregulated miRNAs represented C14MC and none C19MC. miR-210-3p, miR-512-5p, miR-32-5p, miR-19a-3p, miR-590-3p, miR-379-5p were differentially expressed in LO-PE and cases of small-for-gestational-age newborns, supporting a shared etiology. Expression correlation analysis with the RNA-Seq data (16,567 genes) of the same samples clustered PE-linked miRNAs into five groups. Large notable clusters of miRNA–gene pairs showing directly and inversely correlated expression dynamics suggested potential functional relationships in both scenarios. The first genome-wide study of placental miR-eQTLs identified 66 placental SNVs associated with the expression of neighboring miRNAs, including PE-linked miRNAs miR-30a-5p, miR-210-3p, miR-490-3p and miR-518-5p. This study provided a rich catalog of miRNAs for further in-depth investigations of their individual and joint effect on placental transcriptome. Several highlighted miRNAs may serve as potential biomarkers for pregnancy monitoring and targets to prevent or treat gestational disorders.

Assessment of plasma cell-free DNA and ST2 as parameters in gestational hypertension and preeclampsia.

The objective of this study was to evaluate the differences and predictive efficacy of circulating cell-free DNA (cfDNA) and human suppression of tumorigenesis 2 (ST2) among women with uncomplicated pregnancies and patients with gestational hypertension (GH) or preeclampsia (PE). This study included patients with GH (n = 41), patients with PE (n = 62), and women with uncomplicated pregnancies (n = 148). The cfDNA concentration was determined by qPCR, and the ST2 levels were measured by ELISA. A receiver operating characteristic curve was employed to measure the diagnostic performance of cfDNA and ST2. Our results showed that ST2 but not cfDNA was increased in the middle and third trimesters of normal pregnancy; ST2 and cfDNA were increased in GH and PE patients compared to women with uncomplicated pregnancies. More importantly, plasma cfDNA and ST2 served as diagnostic biomarkers for GH and PE, and the AUCs were 0.883 and 0.734 for GH and 0.838 and 0.816 for PE, respectively. Moreover, their combination significantly elevated the diagnostic efficiency for GH and PE, with AUCs of 0.906 and 0.916, respectively. Plasma cfDNA and ST2 could be used as parameters for GH and PE.

Second-trimester and third-trimester maternal lipid profiles significantly correlated to LGA and macrosomia.

According to the theory of fetal-derived adult diseases, abnormal fetal development might affect the occurrence of diseases in adulthood, and appropriate fetal growth status intrauterine might have a beneficial effect on it. To adapt properly for fetal development, there are numerous changes in the maternal physiology during pregnancy, including blood lipid metabolism. The aim of this study is to evaluate the association between lipid profiles in the second and third trimesters of normal pregnancy and fetal birth weight. The study population was derived from 5695 pregnant women, who maintained routine prenatal care at the women's hospital of Zhejiang University, School of medicine January 1, 2014, and December 31, 2014. The pregnant women in this study all carried uncomplicated singleton pregnancies to at least 37 weeks. The mean (standard deviation) birth weight was 3361.00 (385.94) g; 413 (7.3%) of the infants were large for gestational age, and 330 (5.8%) were macrosomia. On multiple linear regression analysis, positive determinants of birth weight were gravidity, parity, gestational age at delivery, male infant, maternal height, and weight before pregnancy, weight gain during pregnancy, fasting blood glucose (FBG) level, second-trimester cholesterol (TC) and third-trimester triglyceride (TG), gestational albumin (ALB), and third-trimester high-density lipoprotein (HDL-C) levels were each negatively associated with birth weight. On logistic regression analysis, the significant metabolic lipid predictors of delivering a large-for-gestational-age infant were second- and third-trimester TG (aOR = 1.178, 95% CI 1.032-1.344, p = 0.015; aOR = 1.106, 95% CI 1.043-1.173, p = 0.001, respectively) and second- and third-trimester HDL-C level (aOR = 0.655, 95% CI 0.491-0.874, p = 0.004; aOR = 0.505, 95% CI 0.391-0.651, p < 0.001, respectively). Third-trimester TG and HDL-C were stable predictors of large-for-gestational-age infants in stratification analysis. High TG and low HDL-C level during third trimester could be considered as indicators of a high risk of large for gestational age (LGA) and macrosomia, regardless of infant gender. These results suggest that future lifestyle programs in women of reproductive age with a focus on lowering TG levels (i.e., diet, weight reduction, and physical activity) may help to reduce the incidence of LGA and macrosomia.

Circular RNA Sequencing of Maternal Platelets: A Novel Tool for the Identification of Pregnancy-Specific Biomarkers.

In the first trimester of pregnancy, the maternal platelet is directly involved in a positive feedback mechanism that facilitates invasion of the extravillous trophoblast into the maternal spiral arteries. Dysfunctional trophoblast invasion with defective deep placentation is primordial in the etiology of the "great obstetrical syndromes." In this proof-of-concept study, using transcriptome analysis of circular RNA (circRNA) following RNA sequencing of maternal platelets, we tested whether pregnancy-specific circRNA markers could be identified in the first trimester of normal pregnancies. Differential transcript expression analysis of circRNAs, as predicted by Accurate CircRNA Finder Suite, CircRNA Identifier (version 2), and Known and Novel Isoform Explorer, was done using thromboSeq.R with variation of multiple settings. Test performance was checked for (a) de novo circRNA identification using the novel platelet-specific Plt-circR4 as a positive control, (b) complete segregation of groups (pregnant vs nonpregnant) after heat map-dendrogram clustering, (c) identification of pregnancy-specific circRNA markers at a false discovery rate (FDR) <0.05, and (d) confirmation of differentially expressed circRNA markers with an FDR <0.05 by an independent method, reverse transcription-quantitative PCR. Of the differentially expressed circRNAs with P values <0.05, 41 circRNAs were upregulated (logFC >2), and 52 circRNAs were downregulated (logFC less than -2) in first-trimester platelet RNA. Of these, nuclear receptor-interacting protein 1 circRNA covering exons 2 and 3 of the 5'-untranslated region was pregnancy specific with upregulation in first-trimester maternal platelets compared to nonpregnant controls. CircRNA sequencing of first-trimester maternal platelets permits the identification of novel pregnancy-specific RNA biomarkers. Future use could include the assessment of maternal and fetal well-being.

СONSECUTIVE INTEGRATION OF AVAILABLE MICROARRAY DATA FOR ANALYSIS OF DIFFERENTIAL GENE EXPRESSION IN HUMAN PLACENTA

The purpose of the study was to provide the pipeline for processing of publicly available unprocessed data on gene expression via integration and differential gene expression analysis. Data collection from open gene expression databases, normalization and integration into a single expression matrix in accordance with metadata and determination of differentially expressed genes were fulfilled. To demonstrate all stages of data processing and integrative analysis, there were used the data from gene expression in the human placenta from the first and second trimesters of normal pregnancy. The source code for the integrative analysis was written in the R programming language and publicly available as a repository on GitHub. Four clusters of functionally enriched differentially expressed genes were identified for the human placenta in the interval between the first and second trimester of pregnancy. Immune processes, developmental processes, vasculogenesis and angiogenesis, signaling and the processes associated with zinc ions varied in the considered interval between the first and second trimester of placental development. The proposed sequence of actions for integrative analysis could be applied to any data obtained by microarray technology.

Serum progesterone in first trimester of normal pregnancy

Serum progesterone in first trimester of normal pregnancy

Estimation of Reference Interval of Serum Progesterone During Three Trimesters of Normal Pregnancy in a Tertiary Care Hospital of Kolkata

Estimation of Reference Interval of Serum Progesterone During Three Trimesters of Normal Pregnancy in a Tertiary Care Hospital of Kolkata

Human Miscarriage Is Associated With Dysregulations in Peripheral Blood-Derived Myeloid Dendritic Cell Subsets.

Dendritic cells (DC) are critically involved in decisions related to the acceptance or rejection of the foreign fetal antigens by the maternal immune system. However, particularly for human peripheral blood DCs (PBDC), available literature is rather inconsistent and the factors regulating these cells are ill-defined. Here, we investigated the phenotype and functionality of different human PBDC subsets during normal and pathologic pregnancies and studied an involvement of human chorionic gonadotropin (hCG) in PBDC regulation. Peripheral blood samples were obtained from normal pregnant women in all three trimesters, from first trimester miscarriage patients and from healthy non-pregnant women. Samples were analyzed for plasma hCG levels, for regulatory T (Treg) cell numbers, for frequencies of total and mature plasmacytoid (PDC) and myeloid (MDC1 and MDC2) PBDC subsets and for their cytokine secretion. In vitro assays, culturing PDC, MDC1 or MDC2 in the presence of two trophoblast cell lines, placenta explant supernatants or two hCG preparations were performed. The Treg-inducing capability of hCG- or non-hCG-treated stimulated MDC1 was assessed. Total and mature MDC1 and MDC2 frequencies increased during the first and second trimester of normal pregnancy, respectively. Miscarriage was associated with a reduced MDC1 and an increased MDC2 activation profile. PDC were not altered neither during normal pregnancy progression nor during miscarriage. In vitro, the culture of isolated PBDC subsets in the presence of placenta-derived factors impaired the maturation of MDC1 and differentially affected PDC maturation. An inhibitory effect on MDC1 and PDC maturation was also proven for the urine-derived hCG preparation. Finally, we observed a Treg cell elevation during early normal pregnancy that was not present in miscarriages. Stimulated MDC1 induced Treg cells in vitro, however, hCG was not involved in this process. Our findings suggest that during normal pregnancy PBDC subsets are differentially regulated dependent on gestational age. Miscarriage seems to be associated with dysregulations in the myeloid PBDC subsets and with disturbances in Treg cell frequencies. Moreover, our results propose an interdependency between MDC1 and Treg cells during early pregnancy. hCG, although shown to impair MDC1 maturation, does not seem to be a key regulator of PBDC alterations during pregnancy.

Ultrasound Assessment of Placental Thickness in The Last Two Trimesters of Normal Pregnancy and Its Relation with Fetal Outcome

Abstract:Background: The placenta is a vital organ which plays an important role in the normal fetal growth and development process. The aim of work: Is to assess the relation between thickness of the placenta during the 2nd and 3rd trimesters and fetal birth weight and placental weight .Patients & Methods: 50 cases of uncomplicated pregnant women who were attended the outpatient clinic at Zagazig University Maternity Hospital were involved in this cohort study from the period between June 2018 to March 2019;, The thickness of the placenta was measured by trans abdominal ultrasound during second and third trimester .The relation between thickness of the placenta and fetal outcome was examined by Pearson’s correlation. Results: according to our study there was positive relation between thickness of the placenta at the 2ndtrimester and 3rdtrimester with fetal birth weight, placental weight and APGAR score. The fetal outcome was better with normal placental thickness (10th- 90th) in comparison to that with thin (90th) &the incidence of NICU admission increased in thick placenta and thin placenta.Conclusions: The thickness of the placenta by ultrasound can be used beside other biometric parameters in predicting neonatal outcome and measurement of placental parameters should be involved in all routine antenatal ultrasounds.

Characteristics of bile acids metabolism profile in the second and third trimesters of normal pregnancy

PurposeBile acids are a group of cholesterol metabolites functioning as key regulators of glucose, lipid, and energy metabolism. Their homeostatic control is essential to the physiology of the normal pregnancy. Abnormalities of bile acids regulation in pregnancy lead to intrahepatic cholestasis of pregnancy, a serious condition associated with a number of fetal and maternal morbidities. Dysregulation of glucose and lipids is also tied to perturbations in bile acid concentrations. Changes in bile acid metabolic profiles in the second and third trimesters of pregnancy have been incompletely explored. We seek to establish pregnancy-specific normative ranges for a number of bile acids in women in the second and third trimesters and explore changes in their concentrations in the period from 12 to 40 weeks gestation. ProcedureIn this cross-sectional study, a total of 782 normal pregnant women were enrolled including n = 290 in the second trimester (12–28 weeks) and n = 492 in the third trimester (29–40 weeks). The concentrations of 14 bile acids were measured by liquid chromatography and mass spectrometry (LC-MS) and compared at various time points. Reference intervals of these bile acids were calculated using standard statistical techniques. ResultsA reference interval profile of 14 bile acids from a cohort of 782 normal pregnant women was developed. Significant differences in concentration were found between the second trimester and the third trimester. Unconjugated bile acids dominate the bile acid profile in the second trimester, while conjugated bile acids, especially (taurine-conjugated) dominate in the third trimester. 28–31 weeks gestation was the notable change period of bile acid metabolism. ConclusionThis study establishes pregnancy-specific reference intervals for bile acids in the second and third trimesters. As bile acid composition changes with gestational age, this study establishes a foundation for trimester-specific clinical interpretation of bile acid metabolic profiles in pregnant women.

Role of Immune Distribution of Tissue Factor in the Development of Hemostasis during the First Trimester of Normal Pregnancy.

Immunohistochemistry of tissue factor, vimentin, and cytokeratin-8 was studied in the medical abortion material at gestation week 5-10 in 20 healthy women. No expression of tissue factor was found in vimentin-positive decidual cells of the parietal endometrium. By contrast, intensive immunostaining of the TF/FVIIα complex was detected in the marginal layer of Rohr fibrinoid and less intense staining was found in vimentin-positive decidual cells adjacent to the walls of modified spiral arteries in the utero-placental region under conditions of invasion of the interstitial and intravascular cytotrophoblast (marker: cytokeratin-8). In the villi, tissue factor was expressed only in the fibrinoid lumps at sites of the syncytiotrophoblast defects. We demonstrated the formation of local hemostasis system in the uteroplacental region at weeks 5-8. This system creates optimal conditions for external thrombogenesis aimed at realization of the cytotrophoblast invasion and subsequent flow of arterial blood between the villi at the end of the first trimester.

Deregulation of miR-324/KISS1/kisspeptin in early ectopic pregnancy: mechanistic findings with clinical and diagnostic implications

Ectopic pregnancy is a life-threatening condition for which novel screening tools that would enable early accurate diagnosis would improve clinical outcomes. Kisspeptins, encoded by KISS1, play an essential role in human reproduction, at least partially by regulating placental function and possibly embryo implantation. Kisspeptin levels are elevated massively in normal pregnancy and reportedly altered in various gestational pathologic diseases. Yet, the pathophysiologic role of KISS1/kisspeptin in ectopic pregnancy has not been investigated previously. The purpose of this study was to evaluate changes of KISS1/kisspeptin levels in ectopic pregnancy and their underlaying molecular mechanisms and to ascertain the diagnostic implications of these changes. A total of 122 women with normal pregnancy who underwent voluntary termination of pregnancy and 84 patients who experienced tubal ectopic pregnancy were recruited. Measurements of plasma kisspeptins and KISS1 expression analyses in human embryonic/placental tissue were conducted in ectopic pregnancy and voluntary termination of pregnancy control subjects during the early gestational window (<12 weeks). Putative microRNA regulators of KISS1 were predicted in silico, followed by expression analyses of selected microRNAs and validation of repressive interactions invitro. Circulating levels of these microRNAs were also assayed in ectopic pregnancy vs voluntary termination of pregnancy. Circulating kisspeptins gradually increased during the first trimester of normal pregnancy but were reduced markedly in ectopic pregnancy. This profile correlated with the expression levels of KISS1 in human embryonic/placental tissue, which increased in voluntary termination of pregnancy but remained suppressed in ectopic pregnancy. Bioinformatic predictions and expression analyses identified miR-27b-3p and miR-324-3p as putative repressors of KISS1 in human embryonic/placental tissue at <12 weeks gestation, when expression of microRNAs was low in voluntary termination of pregnancy control subjects but significantly increased in ectopic pregnancy. Yet, a significant repressive interaction was documented only for miR-324-3p, occurring at the predicted 3'-UTR of KISS1. Interestingly, circulating levels of miR-324-3p, but not of miR-27b-3p, were suppressed distinctly in ectopic pregnancy, despite elevated tissue expression of the pre-microRNA. A decision-tree model that used kisspeptin and miR-324-3p levels was successful in discriminating ectopic pregnancy vs voluntary termination of pregnancy, with a receiver-operating characteristic area under the curve of 0.95±0.02 (95% confidence interval). Our results document a significant down-regulation of KISS1/kisspeptins in early stages of ectopic pregnancy via, at least partially, a repressive interaction with miR-324-3p. Our data identify circulating kisspeptins and miR-324-3p as putative biomarkers for accurate screening of ectopic pregnancy at early gestational ages.

Trophoblast CD200 expression in successful human pregancies and missed abortions

Presence of the CD200 immune check-point inhibitor at the feto-maternal interface is linked to prevention of spontaneous abortion in mice and humans. In human missed abortions (MA), absence of Th17-driven inflammation has been attributed to expression of villus trophoblast CD200 quantified using immunohistochemistry. While rapid aneuploidy (QF-PCR) testing linked low CD200 to pregnancy failure, data showing normal VT CD200 in first trimester normal pregnancy and in abortion of chromosomally abnormal embryos has not been demonstrated. The present report shows normal CD200 in a 7 week gestation termination with normal male QF-PCR and in a 10 week male trisomy 18 MA.

The Role of Pro- and Antioxidant Systems in the Development of Placental Dysfunction in Human Pregnancy

The pro-and antioxidant systems of the human placenta have been studied in its central and peripheral areas in the state of dysfunction. It has been shown that the intensity of free-radical oxidation (FRO) is 24% higher (p < 0.05) in mitochondria isolated from peripheral placental areas in the case of preterm termination of pregnancy than in placental mitochondria of women with normal pregnancy ending in delivery on due dates. The values of total antioxidant activity in mitochondria isolated from the central and peripheral areas of placentae of women with preterm labor exceeded 1.5-and 1.8-fold the respective values for the placental mitochondria of women with the normal duration of pregnancy. The rate of glutathione peroxidase activity in placental mitochondria of women with preterm labor was lower than in patients with normal duration of pregnancy terminated on due dates. Higher values of intensity of both the FRO processes and the active components of thiobarbituric acid (TBA) were recorded (higher by 42% and 62%, respectively) in the postmitochondrial fraction in the peripheral area of placentae of women with spontaneous termination of pregnancy, compared with the placentae of women with uncomplicated duration of pregnancy with labor on due date. No differences have been observed in the intensity of oxidative modification of placental proteins in both the periphery and the center in the placentae of women from the studied groups. The rate of glutathione peroxidase activity in the placenta of women with spontaneous termination of pregnancy was more than twice as high as the activity of this enzyme during the first trimester of normal pregnancy and remained high during the second and third trimesters. The activity of the enzyme did not depend on its localization (center or periphery) in placentae of women participating in the study. The values of glutathione transferase activity in the placentae increased in the course of normal pregnancy but remained at the level of the first trimester in the central and peripheral areas in the case of a miscarriage at different gestational terms. Our findings allow us to suggest that oxidative stress developing in placenta from its center to periphery plays a key role in the pathogenesis of placental dysfunction, mainly, due to the glutathione-dependent component of the placental antioxidant defense.