Trophoblast invasion of the uterine extracellular matrix, a critical process of human implantation and essential for fetal development, is a striking example of controlled invasiveness. To identify molecules that regulate trophoblast invasion, mRNA signatures of trophoblast cells isolated from first trimester (high invasiveness) and term placentae (no/low invasiveness) were compared using U95A GeneChip microarrays yielding 220 invasion/migrationrelated genes. In this 'invasion cluster', KiSS-1 and its G-protein-coupled receptor KiSS-1R were expressed at higher levels in first trimester trophoblasts than at term of gestation. Receptor and ligand mRNA and protein were localized to the trophoblast compartment. In contrast to KiSS-1, which is only expressed in the villous trophoblast, KiSS-1R was also found in the extravillous trophoblast, suggesting endocrine/paracrine activation mechanisms. The primary translation product of KiSS-1 is a 145 amino acid polypeptide (Kp-145), but shorter kisspeptins (Kp) with 10, 13, 14 or 54 amino acid residues may be produced. We identified Kp-10, a dekapeptide derived from the primary translation product, in conditioned medium of first trimester human trophoblast. Kp-10, but not other kisspeptins, increased intracellular Ca 2+ levels in isolated first trimester trophoblasts. Kp-10 inhibited trophoblast migration in an explant as well as transwell assay without affecting proliferation. Suppressed motility was paralleled with suppressed gelatinolytic activity of isolated trophoblasts. These results identifed Kp-10 as a novel paracrine/endocrine regulator in fine-tuning trophoblast invasion generated by the trophoblast itself.
The DALI Lifestyle Study Context: Lifestyle approaches for preventing gestational diabetes mellitus (GDM) have produced mixed results. Objective: The aim of this study was to compare the effectiveness of three lifestyle interventions (Healthy eating (HE), Physical activity (PA) and both HE and PA (HE+PA)) with usual care (UC) in reducing GDM risk. Design: Multicentre Randomised Controlled Trial 2012-2014: The Dali Lifestyle Study Setting: Antenatal clinics across 11 centres in 9 European countries Patients: Consecutive pregnant women <20 weeks gestation with a BMI≥29 kg/m 2 and without GDM by IADPSG criteria (n=436).Intervention: Women were randomized, stratified by site, to Control, HE, PA or HE+PA. Women received 5 face-to-face and up to 4 telephone coaching sessions, based on the principles of motivational interviewing. Gestational weight gain (GWG) <5kg was targeted. Coaches received standardized training and an intervention toolkit tailored to their culture/language. Main outcome measures: GWG at 35-37 weeks, fasting glucose and insulin sensitivity (HOMA-IR) at 24-28 weeks. Results: We randomized 108 women to HE&PA, 113 to HE, 110 to PA and 105 to UC. In the HE+PA group, but not HE or PA alone, women achieved substantially less GWG than controls by 35-37 weeks . Despite this reduction there were no improvements in fasting or post-load glucose or,insulin concentrations or HOMA-IR. Birthweight, large and small for gestational age rates were similar. Copyright 2016 DOI: 10.1210/jc.2016 Conclusions: The combined HE+PA intervention was able to limit GWG but did not reduce fasting glycaemia. Lifestyle change alone is unlikely to prevent GDM among women with a BMI≥29 kg/m 2 .PRECIS: We studied pregnant women in a large European multi-centre RCT of physical activity and/or healthy eating and found no effect on GDM risk in spite of significant gestational weight gain limitation INTRODUCTIONGestational diabetes mellitus (GDM), high pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) are independently associated with an increased risk of adverse perinatal outcomes, including macrosomia, operative delivery and shoulder dystocia (1). In GDM, such complications have a continuous relationship with maternal glucose concentrations during the oral glucose tolerance test (OGTT) (2). With the increasing prevalence of obesity in pregnancy and GDM (3), it has become increasingly important to develop evidence based clinical interventions that prevent the development of GDM and minimise excess GWG. The development of type 2 diabetes through intensive lifestyle interventions can be reduced by 58% over 4 years in non-pregnant women who have previously had GDM (4). However, whether GDM can be prevented through antenatal lifestyle interventions, even with limitation in excess GWG, is disputed (5). RCTs have provided variable evidence that lifestyle interventions 'work' (6); likely because of different intervention protocols and study populations. Furthermore, at the moment, no studies are available that assessed, ...
Normal human pregnancy is considered a state of enhanced oxidative stress. In pregnancy, it plays important roles in embryo development, implantation, placental development and function, fetal development, and labor. However, pathologic pregnancies, including gestational diabetes mellitus (GDM), are associated with a heightened level of oxidative stress, owing to both overproduction of free radicals and/or a defect in the antioxidant defenses. This has important implications on the mother, placental function, and fetal well-being. Animal models of diabetes have confirmed the important role of oxidative stress in the etiology of congenital malformations; the relative immaturity of the antioxidant system facilitates the exposure of embryos and fetuses to the damaging effects of oxidative stress. Of note, there are only a few clinical studies evaluating the potential beneficial effects of antioxidants in GDM. Thus, whether or not increased antioxidant intake can reduce the complications of GDM in both mother and fetus needs to be explored. This review provides an overview and updated data on our current understanding of the complications associated with oxidative changes in GDM.
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