Quantitative Proteomics of Maternal Blood Plasma in Isolated Intrauterine Growth Restriction.

Intrauterine growth restriction (IUGR) remains a significant concern in modern obstetrics, linked to high neonatal health problems and even death, as well as childhood disability, affecting adult quality of life. The role of maternal and fetus adaptation during adverse pregnancy is still not completely understood. This study aimed to investigate the disturbance in biological processes associated with isolated IUGR via blood plasma proteomics. The levels of 125 maternal plasma proteins were quantified by liquid chromatography-multiple reaction monitoring mass spectrometry (LC-MRM MS) with corresponding stable isotope-labeled peptide standards (SIS). Thirteen potential markers of IUGR (Gelsolin, Alpha-2-macroglobulin, Apolipoprotein A-IV, Apolipoprotein B-100, Apolipoprotein(a), Adiponectin, Complement C5, Apolipoprotein D, Alpha-1B-glycoprotein, Serum albumin, Fibronectin, Glutathione peroxidase 3, Lipopolysaccharide-binding protein) were found to be inter-connected in a protein-protein network. These proteins are involved in plasma lipoprotein assembly, remodeling, and clearance; lipid metabolism, especially cholesterol and phospholipids; hemostasis, including platelet degranulation; and immune system regulation. Additionally, 18 proteins were specific to a particular type of IUGR (early or late). Distinct patterns in the coagulation and fibrinolysis systems were observed between isolated early- and late-onset IUGR. Our findings highlight the complex interplay of immune and coagulation factors in IUGR and the differences between early- and late-onset IUGR and other placenta-related conditions like PE. Understanding these mechanisms is crucial for developing targeted interventions and improving outcomes for pregnancies affected by IUGR.

Extracellular DNA levels and cytokine profiles in preterm birth: a cohort study.

PURPOSE: The content of eight different cytokines, cell-free DNA (cfDNA) and cell-free fetal DNA (cffDNA) in women's plasma during preterm birth (PB) was studied. The purpose of this study was to identify the relationships between the investigated factors and determine their prognostic significance. METHODS: Venous blood samples were collected from 45 women with PB and 35 women with full-term labor at 22-31 and 32-36 weeks of gestation, as well as from 17 women during labor at 39-40 weeks of gestation. The concentration of IL-2, IL-4, IL-6, IL-8, IL-10, GM-CSF, IFN-γ and TNF-α cytokines in peripheral blood plasma was measured by multiplex method. The level of cfDNA and cffDNA was evaluated using PCR analysis. RESULTS: It was found that, the level of IL-6, IL-8 and cfDNA in the blood was significantly increased in women with PB at 22-31 weeks of gestation (p = 0.044, p = 0.001, p < 0.001) and 32-36 weeks of gestation (p = 0.025, p = 0.001, p = 0.002) compared to women with physiological pregnancy at the same terms. The level of cffDNA (p = 0.014) was significantly increased in women with PB at 32-36 weeks of gestation. The IL-8 content had a significant correlation with the cfDNA level in women with PB at all stages of labor and with the cffDNA level in the group who gave birth at 32-36 weeks of gestation. There was no correlation between IL-8, cfDNA and cffDNA, but there was consistency with other cytokines at all studied terms and during delivery in the term-delivery group. CONCLUSION: The results of the study suggest that cfDNA is a potential marker of PB and show that the aberrant relationship between cfDNA and IL-8 may be important in the genesis of PB.

Synthetic osmotic dilators for cervical preparation prior to abortion-An international multicentre observational study.

OBJECTIVES: To evaluate the outcomes with the use of Dilapan-S for cervical preparation prior to medical or surgical abortion. STUDY DESIGN: International, multicentre, prospective observational study in women between 6 + 0-24 + 0 weeks' gestation. The study was conducted across 7 study sites in 4 countries, between 1/5/2015 to 31/12/2016. The primary outcomes studied were the number of dilators used and the duration required for cervical preparation prior to abortion. Secondary outcomes were complications of dilator use and infection. Participants were followed-up for 4 weeks post procedure to capture any delayed complications. RESULTS: A total of 483 women were enrolled with 439 women eligible for analysis. Medical abortion was performed in 38% (n = 165) women and surgical abortion in 62% (n = 274). For medical abortions and surgical abortions, an average of 3 osmotic dilators for time interval of 4-7 hours provided effective cervical preparation. Medical abortions were performed as day-case procedures (<12 h) in 81% of women. There was no difference in using either adjunctive misoprostol or Dilapan-S followed by misoprostol for cervical ripening effect to achieve complete medical abortion. Dilapan-S permitted surgical abortions to be performed as same-day procedures (<12 h), in 85% of women regardless of gestational age and without the need to use adjunctive or additional misoprostol. There were no serious adverse events reported with the use of Dilapan-S, including in women with a previous caesarean section. The overall infectious morbidity was 0.9% of cases with no causal relationship with the use of synthetic osmotic dilator use (for a length <24 h). In addition, Dilapan-S was reported as easy to insert and remove in over 90% of women. CONCLUSION: Dilapan-S is a safe and effective method for cervical preparation for medical and surgical abortions up to 24 weeks' gestation. It allows medical and surgical abortions to be performed as day case procedures and is associated with a low complication rate. Future research should aim at directly comparing Dilapan-S and preferred pharmacological agents in a randomised controlled trial.

Ultrastructural and Immunohistochemical Features of Telocytes in Placental Villi in Preeclampsia.

A new cell type, interstitial Cajal-like cell (ICLC), was recently described in different organs. The name was recently changed to telocytes (TCs), and their typical thin, long processes have been named telopodes (Tp). TCs regulate the contractile activity of smooth muscle cells and play a role in regulating vessel contractions. Although the placenta is not an innervated organ, we believe that TCs are present in the placenta. We studied placenta samples from physiological pregnancies and in different variants of preeclampsia (PE). We examined these samples using light microscopy of semi-thin sections, transmission electron microscopy, and immunohistochemistry. Immunohistochemical examination was performed with primary antibodies to CD34, CD117, SMA, and vimentin, and TMEM16a (DOG-1), the latter was used for the diagnosis of gastrointestinal stromal tumours (GIST) consisting of TCs. We have identified a heterogenetic population of ТСs in term placentas, as these cell types differed in their localization, immunophenotype and ultrastructural characteristics. We assume TMEM16a could be used as the marker for identification of TCs. In PE we have revealed telocyte-like cells with ultrastructural signs of fibrocytes (significant process thickening and the granular endoplasmic reticulum content was increased) and a loss of TMEM16a immunohistochemical staining.

The role of extracellular inducer of matrix metalloproteinases in premature rupture of membranes.

OBJECTIVE: To investigate the role of matrix metalloproteinases (MMP-2, MMP-9) and their inducer (CD147) in premature rupture of membranes (PROM) at term labor. METHODS: In a cross-sectional study, 24 women aged 19-39, with 37-40-week pregnancy, and no clinical and histological signs of chorioamnionitis, were divided into two groups with and without PROM. The histological and immunohistochemical study of the fetal membranes was performed with polyclonal rabbit antibodies to MMP-2/MMP-9 and monoclonal rabbit antibodies to CD147. RESULTS: The analysis of MMP revealed the increase of MMP-9 expression in the amniotic epithelium during premature membrane rupture both in rupture area, and beyond it, and increased MMR-2 expression in the mesodermal cells. We also found high level of CD147 in the amniotic epithelium in PROM group. The above-mentioned changes were found in all areas of fetal membranes, regardless of the rupture localization. CONCLUSIONS: The study results demonstrate the increased expression of MMR-2 and MMR-9, which regulate the catabolism of fetal membrane extracellular matrix proteins, in amniotic membranes of women with PROM at term labor. The increased expression of CD147 may be one of the mechanisms triggering PROM in the absence of infection.