Functional evidence for two distinct mechanisms of action of progesterone and selective progesterone receptor modulator on uterine leiomyomas.

OBJECTIVE: To study the specific mechanisms through which progesterone and selective progesterone receptor modulators impact the growth, synthesis, and accumulation of the extracellular matrix in uterine leiomyomas. DESIGN: Laboratory study. SETTING: Academic Research Institutions. PATIENTS (S): This study involved reproductive-age women diagnosed with infertility associated uterine leiomyomas who underwent myomectomy either after selective progesterone receptor modulator ulipristal acetate (UA) treatment or without any pharmacological pretreatment. Control samples included healthy myometrium tissue (n = 100). Specimens were obtained from the Department of Reproduction and Gynecological Endocrinology and Biobank, Medical University of Bialystok, Poland. INTERVENTIONS: Daily (5 mg/d) UA treated for 2 months (n = 100) and untreated (n = 150) patients with uterine leiomyomas or normal healthy myometrium (n = 100) tissue samples immediately after surgery were collected for transcriptional analysis and assessments. MAIN OUTCOME MEASURES: Progesterone-induced activation of the signaling pathways related to uterine leiomyomas extracellular matrix synthesis, deposition, and growth, as well as the expression profile of progesterone receptors in uterine leiomyomas, were assessed. RESULTS: The results indicated that progesterone activated the transforming growth factor-ß and SMAD3 signaling pathways and promoted proliferation, growth, and extracellular matrix remodeling in uterine leiomyomas by up-regulating SMAD3, transforming growth factor-ß (TGF-ß) receptor type 1 and II, Ras homolog A, vascular endothelial growth factor, or increasing the fibrosis-related gene collagen, type I, ɑ-1, and procollagen, type I, ɑ-1 production. In contrast, UA had inhibitory effects on these processes. The study also showed that both nuclear and membrane progesterone receptors play distinct roles in uterine leiomyoma pathobiology. CONCLUSIONS: We showed that both nuclear and membrane progesterone receptors were relevant in the treatment of uterine leiomyomas, especially when combined with selective progesterone receptor modulators. Novel therapeutic approaches combining selective progesterone receptor modulators with or without direct and indirect extracellular matrix targeting through selected specifically TGF-ß and SMAD3 (SMAD3, TGF-ß receptor types 1 and II, Ras homolog A, vascular endothelial growth factor, collagen, type I, ɑ-1) signaling pathways could therefore be a treatment option for uterine leiomyomas.

Exploring new perspectives on congenital diaphragmatic hernia: A comprehensive review.

Congenital diaphragmatic hernia (CDH) represents a developmental anomaly that profoundly impacts the embryonic development of both the respiratory and cardiovascular systems. Understanding the influences of developmental defects, their origins, and clinical consequences is of paramount importance for further research and the advancement of therapeutic strategies for this condition. In recent years, groundbreaking studies in the fields of metabolomics and genomics have significantly expanded our knowledge regarding the pathogenic mechanisms of CDH. These investigations introduce novel diagnostic and therapeutic avenues. CDH implies a scarcity of available information within this domain. Consequently, a comprehensive literature review has been undertaken to synthesize existing data, providing invaluable insights into this rare disease. Improved comprehension of the molecular underpinnings of CDH has the potential to refine diagnostic precision and therapeutic interventions, thus potentially enhancing clinical outcomes for CDH patients. The identification of potential biomarkers assumes paramount significance for early disease detection and risk assessment in CDH, facilitating prompt recognition and the implementation of appropriate interventions. The process of translating research findings into clinical practice is significantly facilitated by an exhaustive literature review. It serves as a pivotal step, enabling the integration of novel, more effective diagnostic and therapeutic modalities into the management of CDH patients.

Identification of MicroRNA Profiles in Fetal Spina Bifida: The Role in Pathomechanism and Diagnostic Significance.

Distinct miRNA expression patterns may reflect anomalies related to fetal congenital malformations such as spinal bifida (SB). The aim of this preliminary study was to determine the maternal miRNA expression profile of women carrying fetuses with SB. Therefore, six women carrying fetuses with SB and twenty women with euploid healthy fetuses were enrolled in this study. Using NanoString technology, we evaluated the expression level of 798 miRNAs in both plasma and amniotic fluid samples. A downregulation of miR-1253, miR-1290, miR-194-5p, miR-302d-3p, miR-3144-3p, miR-4536-5p, miR-548aa + miR-548t-3p, miR-548ar-5p, miR-548n, miR-590-5p, miR-612, miR-627-5p, miR-644a, and miR-122-5p, and an upregulation of miR-320e, let-7b-5p, miR-23a-3p, miR-873-3p, and miR-30d-5p were identified in maternal amniotic fluid samples in SB when compared to the control group. The target genes of these miRNAs play a predominant role in regulating the synthesis of several biological compounds related to signaling pathways such as those regulating the pluripotency of stem cells. Moreover, the maternal plasma expression of miR-320e was increased in pregnancies with SB, and this marker could serve as a valuable non-invasive screening tool. Our results highlight the SB-specific miRNA signature and the differentially expressed miRNAs that may be involved in SB pathogenesis. Our findings emphasize the role of miRNA as a predictive factor that could potentially be useful in prenatal genetic screening for SB.

The Role of Oxidative Stress in Trisomy 21 Phenotype.

Extensive research has been conducted to gain a deeper understanding of the deregulated metabolic pathways in the development of trisomy 21 (T21) or Down syndrome. This research has shed light on the hypothesis that oxidative stress plays a significant role in the manifestation of the T21 phenotype. Although in vivo studies have shown promising results in mitigating the detrimental effects of oxidative stress, there is currently a lack of introduced antioxidant treatment options targeting cognitive impairments associated with T21. To address this gap, a comprehensive literature review was conducted to provide an updated overview of the involvement of oxidative stress in T21. The review aimed to summarize the insights into the pathogenesis of the Down syndrome phenotype and present the findings of recent innovative research that focuses on improving cognitive function in T21 through various antioxidant interventions. By examining the existing literature, this research seeks to provide a holistic understanding of the role oxidative stress plays in the development of T21 and to explore novel approaches that target multiple aspects of antioxidant intervention to improve cognitive function in individuals with Down syndrome. The guides -base systematic review process (Hutton et al. 2015).

Plasma Levels of Metalloproteinase 3 (MMP-3) and Metalloproteinase 7 (MMP-7) as New Candidates for Tumor Biomarkers in Diagnostic of Breast Cancer Patients.

Matrix metalloproteinases (MMPs) are a group of enzymes that mediate both physiological and pathological processes such as carcinogenesis. The role of matrix metalloproteinase-3 (MMP-3) and (MMP-7) in the pathogenesis of breast cancer (BC) has been demonstrated, suggesting that they may be considered as potential markers of this condition. The aim of this study was to assess plasma concentrations and diagnostic utility of MMP-3 and MMP-7 in 100 patients with early-stage breast cancer with Luminal A subtype or Luminal B HER-negative subtype, before and after surgical treatment, and in the following control groups: patients with a benign tumor (fibroadenoma) and healthy subjects. The concentrations of MMP-3 and MMP-7 were referenced to the levels of the widely recognized marker for BC diagnosis CA 15-3. MMP-3 and MMP-7 was measured by ELISA method and CA 15-3 by CMIA. Plasma levels of MMP-7 were significantly higher in Luminal A and Luminal B HER2-negative subtype breast cancer patients as compared to the healthy group. MMP-7 demonstrated comparable but mostly higher to CA 15-3 or MMP-3 values of diagnostic sensitivity, specificity, positive and negative predictive values and AUC (0.6888 for Luminal A subtype; 0.7612 for Luminal B HER2-negative; 0.7250 for BC total group, respectively) in the groups tested. The combined use of the tested parameters resulted in a further increase in diagnostic criteria and AUC. These results suggest the usefulness of combining MMP-7 with CA 15-3 in the diagnostics of breast cancer, especially in Luminal B HER2-negative subtypes patients, as a new candidate for tumor markers.

Future Perspectives in Oxidative Stress in Trisomy 13 and 18 Evaluation.

Autosomal aneuploidies are the most frequently occurring congenital abnormalities and are related to many metabolic disorders, hormonal dysfunctions, neurotransmitter abnormalities, and intellectual disabilities. Trisomies are generated by an error of chromosomal segregation during cell division. Accumulating evidence has shown that deregulated gene expression resulting from the triplication of chromosomes 13 and 18 is associated with many disturbed cellular processes. Moreover, a disturbed oxidative stress status may be implicated in the occurrence of fetal malformations. Therefore, a literature review was undertaken to provide novel insights into the evaluation of trisomy 13 (T13) and 18 (T18) pathogeneses, with a particular concern on the oxidative stress. Corresponding to the limited literature data focused on factors leading to T13 and T18 phenotype occurrence, the importance of oxidative stress evaluation in T13 and T18 could enable the determination of subsequent disturbed metabolic pathways, highlighting the related role of mitochondrial dysfunction or epigenetics. This review illustrates up-to-date T13 and T18 research and discusses the strengths, limitations, and possible directions for future studies. The progressive unification of trisomy-related research protocols might provide potential medical targets in the future along with the implementation of the foundation of modern prenatal medicine.

Metformin Intervention-A Panacea for Cancer Treatment?

The molecular mechanism of action and the individual influence of various metabolic pathways related to metformin intervention are under current investigation. The available data suggest that metformin provides many advantages, exhibiting anti-inflammatory, anti-cancer, hepatoprotective, cardioprotective, otoprotective, radioprotective, and radio-sensitizing properties depending on cellular context. This literature review was undertaken to provide novel evidence concerning metformin intervention, with a particular emphasis on cancer treatment and prevention. Undoubtedly, the pleiotropic actions associated with metformin include inhibiting inflammatory processes, increasing antioxidant capacity, and improving glycemic and lipid metabolism. Consequently, these characteristics make metformin an attractive medicament to translate to human trials, the promising results of which were also summarized in this review.

miRNAs as Predictive Factors in Early Diagnosis of Gestational Diabetes Mellitus.

Introduction: Circulating miRNAs are important mediators in epigenetic changes. These non-coding molecules regulate post-transcriptional gene expression by binding to mRNA. As a result, they influence the development of many diseases, such as gestational diabetes mellitus (GDM). Therefore, this study investigates the changes in the miRNA profile in GDM patients before hyperglycemia appears. Materials and Methods: The study group consisted of 24 patients with GDM, and the control group was 24 normoglycemic pregnant women who were matched for body mass index (BMI), age, and gestational age. GDM was diagnosed with an oral glucose tolerance test between the 24th and 26th weeks of pregnancy. The study had a prospective design, and serum for analysis was obtained in the first trimester of pregnancy. Circulating miRNAs were measured using the NanoString quantitative assay platform. Validation with real time-polymerase chain reaction (RT-PCR) was performed on the same group of patients. Mann-Whitney U-test and Spearman correlation were done to assess the significance of the results. Results: Among the 800 miRNAs, 221 miRNAs were not detected, and 439 were close to background noise. The remaining miRNAs were carefully investigated for their average counts, fold changes, p-values, and false discovery rate (FDR) scores. We selected four miRNAs for further validation: miR-16-5p, miR-142-3p, miR-144-3p, and miR-320e, which showed the most prominent changes between the studied groups. The validation showed up-regulation of miR-16-5p (p<0.0001), miR-142-3p (p=0.001), and miR-144-3p (p=0.003). Conclusion: We present changes in miRNA profile in the serum of GDM women, which may indicate significance in the pathophysiology of GDM. These findings emphasize the role of miRNAs as a predictive factor that could potentially be useful in early diagnosis.

Plasma Levels and Diagnostic Utility of VEGF in a Three-Year Follow-Up of Patients with Breast Cancer.

Breast cancer is the most common malignancy in women globally. The increasing worldwide incidence of this type of cancer illustrates the challenge it represents for healthcare providers. Therefore, new tumor markers are constantly being sought. The aim of this study was to assess plasma concentrations and the diagnostic power of VEGF in 100 patients with early-stage breast cancer, both before and after surgical treatment and during a three-year follow-up. The control groups included 50 subjects with benign breast tumors (fibroadenoma) and 50 healthy women. The VEGF concentration was determined using enzyme-linked immunosorbent assay (ELISA) and the CA 15-3 concentration was determined by chemiluminescent microparticle immunoassay (CMIA). We observed significantly higher preoperative plasma concentrations of VEGF and CA 15-3 in patients with breast cancer. VEGF, similar to CA 15-3, demonstrated high diagnostic utility in the assessment of the long-term efficacy of surgical removal of the tumor. Determinations of VEGF had the highest diagnostic usefulness in the detection of breast cancer recurrence (SE 40%, SP 92%, PPV 67%, NPV 79%). Additionally, the highest values of SE, NPV and AUC were observed during the combined analysis with CA 15-3 (60%; 84%; 0.7074, respectively). Our study suggests a promising diagnostic utility of VEGF in the early stages of breast cancer and in the evaluation of the efficacy of the surgical treatment of breast cancer as well as the detection of breast cancer recurrence, particularly in a combined analysis with CA 15-3 as a new diagnostic panel.

Novel Approaches to an Integrated Route for Trisomy 21 Evaluation.

Trisomy 21 (T21) is one of the most commonly occurring genetic disorders, caused by the partial or complete triplication of chromosome 21. Despite the significant progress in the diagnostic tools applied for prenatal screening, commonly used methods are still imprecise and involve invasive diagnostic procedures that are related to a maternal risk of miscarriage. In this case, novel prenatal biomarkers are still being evaluated using highly specialized techniques, which could increase the diagnostic usefulness of biochemical prenatal screening for T21. From the other hand, the T21's pathogenesis, caused by the improper division of genetic material, disrupting many metabolic pathways, could be further evaluated with the use of omics methods, which could result in bringing relevant insights for the evaluation of potential medical targets. Accordingly, a literature search was undertaken to collect novel information about prenatal screening for Down syndrome with the use of advanced technology, with a particular emphasis on the evaluation of novel screening biomarkers and the discovery of potential medical targets. These meta-analyses are focused on novel approaches designed with the use of omics techniques, representing the most rapidly developing and promising field in research today. Considering the limitations and progress of these methods, the use of omics techniques in evaluating T21 pathogenesis could bring beneficial results in prenatal screening, simultaneously uncovering novel potential medical targets.

Assessment of different markers of ovarian reserve in women with papillary thyroid cancer treated with radioactive iodine.

Treatment with radioactive iodine (RAI) in women with differentiated thyroid cancer is associated with decreased serum concentrations of anti-Müllerian hormone (AMH); however, other markers have not been investigated. Therefore, this study aimed to evaluate the effect of RAI treatment on antral follicle count (AFC) and the serum concentration of inhibin B, follicle-stimulating hormone (FSH), and AMH in women with papillary thyroid cancer (PTC) treated with RAI. We examined 25 women at a median age of 33 years treated with a single dose of RAI. We divided the participants into women over (n = 11) and under 35 years of age (n = 14). Serum concentrations of inhibin B, FSH, AMH, and AFC were assessed at baseline and 1 year after RAI treatment. We found decreased AFC (P = 0.03), serum levels of AMH (P < 0.01), inhibin B (P = 0.03), but not FSH (P = 0.23), 1 year after RAI treatment in comparison to baseline in the whole group. When we compared serum levels of AMH in younger vs older women separately, we observed a significant reduction of this hormone's serum level after RAI treatment in both groups (P < 0.01; P = 0.04, respectively). We concluded that RAI treatment significantly impacts the functional ovarian reserve in premenopausal women with PTC.

Prenatal Screening of Trisomy 21: Could Oxidative Stress Markers Play a Role?

Despite significant progress in trisomy 21 (T21) diagnostic tools, amniocentesis is still used for the confirmation of an abnormal fetal karyotype. Invasive tests carry the potential risk of miscarriage; thus, screening biomarkers are commonly used before undergoing invasive procedures. In our study, we investigated the possible application of oxidative stress markers in the prenatal screening of trisomy 21. The DNA/RNA oxidative stress damage products (OSDPs), advanced glycation end (AGE) products, ischemia-modified albumin (IMA), alfa-1-antitrypsin (A1AT), asprosin, and vitamin D concentrations were measured in both maternal plasma and amniotic fluid in trisomy 21 (T21) and euploid pregnancies. The obtained results indicated increased levels of DNA/RNA OSDPs and asprosin with simultaneous decreased levels of vitamin D and A1AT in the study group. The diagnostic utility of the plasma measurement based on the area under the received operative characteristic (ROC) curve (AUC) calculation of asprosin (AUC = 0.965), IMA (AUC = 0.880), AGE (AUC = 0.846) and DNA/RNA OSDPs (AUC = 0.506) in T21 screening was demonstrated. The obtained results indicate a potential role for the application of oxidative stress markers in the prenatal screening of T21 with the highest screening utility of plasma asprosin.

Amniotic fluid metabolic fingerprinting indicated metabolites which may play a role in the pathogenesis of foetal Down syndrome - a preliminary report.

OBJECTIVES: Down syndrome is the most common human chromosomal aberration. It is commonly known that it is a genetic- based disease, but still, pathomechanisms which lead to observed disorders have not been explained. The objective of this study was to determine the metabolic fingerprinting of the amniotic fluid women carrying foetuses with Down syndrome (DS). MATERIAL AND METHODS: The study and control groups consisted of women who underwent routine amniocentesis between the 15th and 18th week of gestation. After analysis of the karyotyping results, 13 women with foetal DS were chosen. For the control group, 13 healthy patients with uncomplicated pregnancies who delivered healthy newborns at term was selected. Amniotic fluid was analyzed using liquid chromatography combined with high resolution mass spectrometry. RESULTS: In the amniotic fluid of women with foetal DS compared to patients with healthy foetuses, we reported significant differences in the level of four metabolites: methylhistidine, hexanoylcarnitine, diacetylspermine and p-cresol sulfate which may be connected with improper development of nervous system and muscles. We detected bacterial metabolite, which support the latest thesis about non-sterile intrauterine environment. CONCLUSIONS: Based on our findings, we hypothesise that differences in the level of four metabolites in the amniotic fluid may play role in the pathogenesis of DS. Defining their potential as biochemical pathogenic factors of DS requires further investigation of the biological pathways involving in the foetal development.

The Significance of Apolipoprotein E Measurement in the Screening of Fetal Down Syndrome.

Prenatal screening for Down syndrome (DS) is based on both noninvasive and invasive methods. Noninvasive, cell-free fetal DNA genetic tests are expensive, whereas biochemical methods remain imprecise. Amniocentesis is the most frequently used invasive diagnosis procedure, characterized by 99.8% diagnostic efficiency and less than 1% risk of miscarriage. The aim of this study was to evaluate the screening value of apolipoprotein E (ApoE) as a potential noninvasive biomarker for prenatal DS assessment. This study was conducted on a group of female patients who decided to undergo routine amniocentesis between the 15th and 18th week of pregnancy at the Department of Reproduction and Gynecological Endocrinology of the Medical University of Bialystok, Poland. For the purpose of this study, 20 women with DS fetuses were selected as the study group, and 20 healthy pregnant women with euploid fetus karyotypes as the control group. The plasma levels of ApoE were significantly higher in the study group compared to healthy subjects (p < 0.05). The area under the receiver operating characteristic (ROC) curve was 0.978 (p < 0.001), with the cut-off set to 1.37 mg/mL, which was characterized by 80% of sensitivity and 100% of specificity. The high sensitivity and specificity demonstrate the screening utility of maternal ApoE concentration in prenatal fetal DS screening.

Diagnostic Power of Cytokine M-CSF, Metalloproteinase 2 (MMP-2) and Tissue Inhibitor-2 (TIMP-2) in Cervical Cancer Patients Based on ROC Analysis.

Macrophage colony-stimulating factor (M-CSF), matrix metalloproteinase-2 (MMP-2) and its specific tissue inhibitor (TIMP-2) may play an important role in the pathogenesis of cancer disease. We investigated the plasma levels and diagnostic power (ROC curve analysis) of M-CSF, MMP-2, TIMP-2 and tumor markers CA 125 and SCC-Ag in cervical cancer (CC) patients as compared to control group. The study included 89 patients with cervical cancer. The control group consisted of 50 healthy, untreated women. The plasma levels of M-CSF, MMP-2 and TIMP-2 were determined using ELISA, CA 125 and SCC-Ag - by CMIA method. The median levels of M-CSF, TIMP-2, SCC-Ag and CA 125 in the entire group of CC were significantly different than compared to the healthy women group. MMP-2 showed the highest value of sensitivity from all examined parameters (in stage I of CC - 93.10%, II - 82.76%, III and IV - 96.88%, total group - 92.05%). The highest specificity was obtained by M-CSF (86%). The area under the ROC curve (AUC) of M-CSF (0.8051) was the largest of all the tested parameters (even higher than commonly used tumor markers) in the group of cervical cancer. The combination of M-CSF, MMP-2 or TIMP-2 with SCC antigen resulted in an increase AUCs in all cases (0.8760;0.7880;0.8081;respectively). The findings of this study suggest the usefulness of all examined parameters in the diagnostics of CC patients. Out of the tested substances, M-CSF also appears to be the best candidate for cancer diagnostics in all stages of the disease, based on ROC analysis.

Plasma Levels and Tissue Expression of Selected Cytokines, Metalloproteinases and Tissue Inhibitors in Patients With Cervical Cancer.

BACKGROUND: Cytokines, metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) take part in many processes involved in tumor progression and invasion such as degradation of the extracellular matrix, influence on immune cells associated with tumor tissue, and angiogenesis. Thus, the aim of this study was to compare the concentration of plasma levels and tissue expression of macrophage colony-stimulating factor (M-CSF), vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMP)-2 and MMP9, and their tissue inhibitors TIMP1 and TIMP2 in patients with cervical cancer, patients with high-grade cervical intraepithelial dysplasia (CIN3) and patients with ectropion. PATIENTS AND METHODS: Concentration and expression of all tested parameters was measured in serum with enzyme-linked immunosorbent assay (ELISA) and in tissue with immunohistochemistry method. RESULTS: The epithelial expression of M-CSF and TIMP1 in cancer tissue was much stronger as compared to that in ectropion and CIN3. In the case of MMP2, lack of or weak expression in epithelial cells was observed in all tested groups. Our studies showed statistical differences of tested parameters in tissue expression and in plasma concentrations in patients with cervical cancer, patients with CIN3 and patients with ectropion. Moreover, data revealed positive correlation between plasma level and cervical cancer cell expression of VEGF. CONCLUSION: Our findings indicate a potential role of all the proteins tested here in cervical cancer diagnosis, especially VEGF. However, further studies will show whether they play a role in the progression of cancerous changes in epithelial tissue of the cervix.

Oxytocin antagonism reverses the effects of high oestrogen levels and oxytocin on decidualization and cyclooxygenase activity in endometrial tissues.

RESEARCH QUESTION: What is the in-vitro effect of oxytocin receptor (OTR) antagonism on parameters of receptivity in human endometrial explants and endometrial stromal cell lines cultured in oestradiol-rich conditions mimicking ovarian stimulation? DESIGN: Experimental in-vitro study on endometrial tissue explants collected by aspiration biopsy from 30 women undergoing fertility treatment and cultured endometrial tHESC cell line. The study examined the effects of high oestradiol, oxytocin and OTR antagonist on parameters of decidualization (cell viability and prolactin secretion) as well as cyclooxygenase-1/2 (COX-1/2) activity and prostaglandin F2α (PGF2α) secretion. Changes in expression of OXTR and COX-2 genes were examined using quantitative polymerase chain reaction (qPCR). RESULTS: In experiments on cultured endometrial cell line, high oestradiol and oxytocin similarly limited the viability of cells. In cultured endometrial explants both also decreased the secretion of prolactin (a marker of decidualization) and augmented endometrial COX-2 activity and formation of PGF2α. Oxytocin antagonist atosiban was confirmed to reverse the above effects, both in the endometrial line and endometrial explants. Addition of atosiban to cultures acted analogously in experiments employing both oxytocin and high oestradiol. CONCLUSIONS: Oxytocin antagonist reversed the effects of high oestradiol and oxytocin on parameters related to endometrial receptivity in conditions mimicking ovarian stimulation. This might point to a novel, endometrium-related mechanism to support embryo implantation achieved by the application of oxytocin antagonist prior to embryo transfer.

The Influence Of Intrauterine Pressure On Embryo Retention In A Catheter After Embryo Transfer.

The retention of the embryo in the transfer catheter after embryo transfer (ET) during in vitro fertilization is a very common phenomenon, encountered by even the most experienced operators, and embryos retained in the transfer catheter or its sleeve require a repeat transfer. The exact mechanism of embryo retention has not been explained. Therefore, the present study aimed to investigate the mechanism of embryo retention in the catheter during embryo transfer by using a transparent uterus model equipped with pressure sensors and a video recorder. The results indicate that pressure changes in the uterine cavity during ET can influence the distribution of the transferred fluid containing the embryo. Under certain conditions, the transferred fluid can flow backward in the catheter, which may lead to retention of the embryo in the catheter.

Simultaneous analysis of bisphenol A fractions in maternal and fetal compartments in early second trimester of pregnancy.

Background Bisphenol A (BPA) is an estrogenic, endocrine-disrupting compound widely used in the industry. It is also a ubiquitous environmental pollutant. Its presence was confirmed in human fetuses, which results from maternal exposure during pregnancy. The mechanisms behind maternal-fetal transfer, and relationships between pregnant women and fetal exposures remain unclear. The aim of this study was to assess the impact of maternal exposure to BPA on the exposure of the fetus. Methods Maternal plasma and amniotic fluid samples were collected from 52 pregnant women undergoing amniocentesis for prenatal diagnosis of chromosomal abnormalities. BPA was measured by gas chromatography-mass spectrometry (GC-MS). The permeability factor - a ratio of fetal-to-maternal BPA concentration - was used as a measure delineating the transplacental transfer of BPA. Results The median concentration of maternal plasma BPA was 8 times higher than the total BPA concentration in the amniotic fluid (8.69 ng/mL, range: 4.3 ng/mL-55.3 ng/mL vs. median 1.03 ng/mL, range: 0.3 ng/mL-10.1 ng/mL). There was no direct relationship between the levels of BPA in maternal plasma and amniotic fluid levels. The permeability factor, in turn, negatively correlated with fetal development (birth weight) (R = -0.54, P < 0.001). Conclusion Our results suggest that the risk of fetal BPA exposure depends on placental BPA permeability rather than the levels of maternal BPA plasma concentration and support general recommendations to become aware and avoid BPA-containing products.

Plasma levels of M-CSF and VEGF in laboratory diagnostics and differentiation of selected histological types of cervical cancers.

BACKGROUND: The search of useful serum biomarkers for the early detection of cervical cancers has been of a high priority. The activation of Macrophage-Colony Stimulating Factor (M-CSF) and Vascular Endothelial Growth Factor (VEGF) is likely involved in the pathogenesis and spread of cancer. We compared the plasma levels of M-CSF and VEGF to the ones of commonly accepted tumor markers CA 125and SCC-Ag in three groups of patients: 1. the cervical cancer group (patients with either squamous cell carcinoma or adenocarcinoma); 2. the cervical dysplasia group; 3. the control group. METHODS: This cohort study included 100 patients with cervical cancer and 55 patients with cervical dysplasia. The control group consisted of 50 healthy volunteers. The plasma levels of VEGF and M-CSF were determined using ELISA, while CA 125 and SCC-Ag concentrations were obtained by the chemiluminescent microparticle immunoassay (CMIA). RESULTS: The median levels of M-CSF and VEGF as well as CA 125 and SCC-Ag in the entire group of cervical cancer patients, were significantly different compared to the healthy women group. In case of both the squamous cell carcinoma and the adenocarcinoma groups, plasma levels of M-CSF and VEGF were higher compared to the control group. No significant differences in the studied parameters between the squamous cell carcinoma and the adenocarcinoma group were observed. The highest sensitivity and specificity were obtained for VEGF (81.18 and 76.00%, respectively) and SCC-Ag (81.18%; 74.00%) in the squamous cell carcinoma group and for VEGF (86.67%; 76.00%) in the adenocarcinoma group. The area under the ROC curve for VEGF was the largest in the adenocarcinoma group followed by the squamous cell carcinoma group (0.9082 and 0.8566 respectively). CONCLUSIONS: Obtained results indicate a possible clinical applicability and a high diagnostic power for the combination of MSC-F, VEGF, CA 125 and SCC-Ag in the diagnosis of both studied types of cervical cancer.