Adenomyosis and adverse perinatal outcomes: increased risk of second trimester miscarriage, preeclampsia, and placental malposition

<p><b>Objective:</b> To evaluate the potential impact of adenomyosis on the pregnancy outcomes by retrospectively investigating adenomyosis-complicated pregnancy cases.</p> <p><b>Methods:</b> We performed a retrospective case–control study. Forty-nine singleton pregnancy cases complicated with adenomyosis were included in this study. The controls (<i>n</i> = 245) were singleton pregnant women without adenomyosis and were frequency matched to adenomyosis cases by age, parity, and the need for assisted reproductive technology for this conception. The incidence of obstetrical complications and delivery and neonatal outcomes were examined.</p> <p><b>Results:</b> Patients in the adenomyosis group were significantly more likely to have a second trimester miscarriage (12.2% versus 1.2%, odds ratio (OR): 11.2, 95% confidence interval (95% CI): 2.2–71.2), preeclampsia (18.3% versus 1.2%, OR: 21.0, 95% CI: 4.8–124.5), placental malposition (14.2% versus 3.2%, OR: 4.9, 95% CI: 1.4–16.3), and preterm delivery (24.4% versus 9.3%, OR: 3.1, 95% CI: 1.2–7.2), compared with the control group.</p> <p><b>Conclusion:</b> Adenomyosis was associated not only with an increased incidence of preterm delivery, as previously reported, but also with an increased risk of second trimester miscarriage, preeclampsia, and placental malposition, which could lead to poor perinatal outcomes.</p

Additional file 1: of Expression of the glucagon-like peptide-1 receptor and its role in regulating autophagy in endometrial cancer

Table S1. Detailed data of participants. Clinicopathological data of 154 patients with endometrial cancer who underwent surgery at the Teikyo University Hospital. These clinical characteristics were obtained by a retrospective review of medical records and the pathological data were obtained by our tissue microarray. (XLSX 14 kb

Concentration of ATX isoform in sera from healthy subjects.

<p>The concentration of total ATX (A), classical ATX (B), and novel ATX (C) antigen and the content ratio of classical ATX (D) and novel ATX (E) relative to total ATX was examined using the sera of healthy subjects (24 men and 33 women). *Statistically significant, as determined using the Mann-Whitney <i>U</i> test (<i>P</i> < 0.01).</p

The concentrations of total ATX, classical ATX, and novel ATX in sera before and after adsorption by R10.23.

<p>The mean ± SD (n = 20) are shown.</p><p>The concentrations of total ATX, classical ATX, and novel ATX in sera before and after adsorption by R10.23.</p

Development of the automated immunoassay for quantitative determination of ATX isoforms.

<p>(A, B) The calibration curves of the classical (A) and novel (B) ATX assays. Rate means the production per second of 4-Methylumbelliferone from 4-methylumbelliferyl phosphate by alkaline phosphatase. (C, D) Dilution linearity of the serum ATX isoform assays. Three different pooled serum samples (samples 1, 2, and 3) were diluted and measured using the classical (C) and novel (D) ATX assays.</p

The concentrations of total ATX, classical ATX, and novel ATX in sera adsorbed by an ATX isoform-specific mAb.

<p>The mean ± SD (n = 28) are shown.</p><p>The concentrations of total ATX, classical ATX, and novel ATX in sera adsorbed by an ATX isoform-specific mAb.</p

The concentrations of the serum total ATX, classical ATX, and novel ATX antigens in males and females.

<p>CLD, chronic liver diseases; FL, follicular lymphoma; DM, diabetes mellitus.</p><p>* <i>p</i> < 0.01 vs Whole male subjects.</p><p>^†<i>p</i> < 0.01 vs Healthy male subjects.</p><p>^‡<i>p</i> < 0.01 vs Healthy female subjects.</p><p>The concentrations of the serum total ATX, classical ATX, and novel ATX antigens in males and females.</p

A Novel Interaction between hScrib and PP1γ Downregulates ERK Signaling and Suppresses Oncogene-Induced Cell Transformation

<div><p>Previous studies have shown that the cell polarity regulator hScrib interacts with, and consequently controls, the ERK signaling pathway. This interaction occurs through two well-conserved Kinase Interacting Motifs, which allow hScrib to bind ERK1 directly, resulting in a reduction in the levels of phospho-ERK. This suggests that hScrib might recruit a phosphatase to regulate this signaling pathway. Using a proteomic approach we now show that Protein Phosphatase 1γ (PP1γ) is a major interacting partner of hScrib. This interaction is direct and occurs through a conserved PP1γ interaction motif on the hScrib protein, and this interaction appears to be required for hScrib's ability to downregulate ERK phosphorylation. In addition, hScrib also controls the pattern of PP1γ localization, where loss of hScrib enhances the nuclear translocation of PP1γ. Furthermore, we also show that the ability of hScrib to interact with PP1γ is important for the ability of hScrib to suppress oncogene-induced transformation of primary rodent cells. Taken together, these results demonstrate that hScrib acts as a scaffold to integrate the control of the PP1γ and ERK signaling pathways and explains how disruption of hScrib localisation can contribute towards the development of human malignancy.</p> </div

hScrib suppresses HPV-16 E7 and EJ-ras induced transformation in cooperation with PP1γ in a RVxF motif-dependent manner.

<p>BRK cells were transfected with EJ-ras alone, HPV-16 E7 plus EJ-ras, HPV-16 E7 plus EJ-ras and wild type hScrib, HPV-16 E7 plus EJ-ras and PP1γ, and HPV-16 E7 plus EJ-ras and wild type hScrib with PP1γ, and HPV-16 E7 plus EJ-ras and PP1γ plus the KADA non-PP1γ binding mutant of hScrib. After three weeks the dishes were fixed and stained and the colonies counted. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0053752#s3" target="_blank">Results</a> represent the mean number of colonies from 3 independent assays and standard deviations are shown.</p

hScrib contains a consensus PP1-binding motif.

<p>A) The schematic shows the arrangement of the functional domains on the hScrib protein, highlighting the LRR, LAPSD and PDZ domains. The putative PP1-binding site, the RVXF (the consensus sequence is K/R/H/N/S V/I/L X F/W/Y) motif is also shown, where X is any amino acid. The hScrib mutant in which the PP1-binding site KLDY was mutated to KADA in order to disrupt the interaction with PP1 is shown. A comparison sequence alignment of the region of hScrib containing the PP1-binding motif indicating its absence in Drosophila also shown. B) In vitro translated and radiolabeled PP1γ was incubated with purified full length GST-hScrib fusion protein (FL), GST-hScrib PDZ1-4 (P1-4), GST-hScrib CT (CT), GST-hScrib L1266Y1268→AA (KADA) and GST alone as a control. After extensive washing the bound PP1γ was ascertained by SDS PAGE and autoradiography. The upper panel shows the autoradiograph, with the input of PP1γ also shown for comparison. The lower panel shows the Coomassie stain of the gel showing the levels of GST fusion protein loading, with the arrows indicating the relevant full length fusion proteins.</p