Uterine scars after caesarean delivery: From histology to the molecular and ultrastructural level.

Uterine rupture during a trial of labor after caesarean delivery (CD) is a serious complication for mother and fetus. The lack of knowledge on histological features and molecular pathways of uterine wound healing has hindered research in this area from evolving over time. We analysed collagen content and turnover in uterine scars on a histological, molecular and ultrastructural level.

A Sustainable Translational Sheep Model for Planned Cesarean Delivery of Contraction-Free Ewes.

We evaluated whether the sheep constitutes a useful translational model to evaluate anatomical and surgical aspects of cesarean delivery (CD) from a human medical perspective with the aim of both maternal and neonatal well-being. Our hypothesis was that CD in contraction-free ewes is not associated with major complications. Primary endpoint was the transferability of anatomical conditions and surgical techniques of CD from the ewe to the human.

Intraoperative ultrasound during repeat cesarean delivery facilitates sampling of uterine scar tissue.

Objectives: Histological examination of uterine scars provides insight into uterine wound healing and helps to develop prevention methods of uterine wall rupture after previous uterine surgery. Therefore, exact intraoperative scar identification is needed for specimen collection from the actual scar tissue. The aim of this study was to correlate pre- and intraoperative ultrasound measurements of the lower uterine segment (LUS) with histological findings of scar tissue and to evaluate the relevance of intraoperative ultrasound.

Optimized RNA isolation of FFPE uterine scar tissues for RNA expression analyses delineated by laser microdissection.

Samples for histological analyses are often formalin-fixed paraffin-embedded (FFPE) and slide-mounted, which complicates RNA extraction for many downstream molecular applications. Furthermore, when the region of interest is extremely small due to isolation with laser microdissection (LMD), extracting RNA of adequate quality and quantity is difficult. We describe an optimized protocol for maximizing RNA output from FFPE tissue devised to identify and analyze gene expression of human maternal uterine scar tissue obtained from uterotomy scars resulting from prior cesarean deliveries.

Placenta Percreta Presents with Neoangiogenesis of Arteries with Von Willebrand Factor-Negative Endothelium.

In placenta percreta cases, large vessels are present on the precrete surface area. As these vessels are not found in normal placentation, we examined their histological structure for features that might explain the pathogenesis of neoangiogenesis induced by placenta accreta spectrum disorders (PAS). In two patients with placenta percreta (FIGO grade 3a) of the anterior uterine wall, one strikingly large vessel of 2 cm length was excised.

Altered DNA methylation within exon 2 is associated with increased mRNA expression in visceral adipose tissue in gestational diabetes.

Overweight/obesity is the main risk factor for gestational diabetes mellitus (GDM). In our cohort of pregnant women with GDM, n = 19, and without, n = 22, we previously reported a significant increase in mRNA expression (+62%) in visceral adipose tissue (VAT) according to GDM, without altered promoter DNA-methylation. Here, we examined methylation status of additional exon 2 regions in VAT and maternal blood.

Maternal but Not Paternal High-Fat Diet (HFD) Exposure at Conception Predisposes for 'Diabesity' in Offspring Generations.

While environmental epigenetics mainly focuses on xenobiotic endocrine disruptors, dietary composition might be one of the most important environmental exposures for epigenetic modifications, perhaps even for offspring generations. We performed a large-scale rat study on key phenotypic consequences from parental (F0) high-caloric, high-fat diet (HFD) food intake, precisely and specifically at mating/conception, focusing on 'diabesity' risk in first- (F1) and second- (F2) generation offspring of both sexes. F0 rats (maternal or paternal, respectively) received HFD overfeeding, starting six weeks prior to mating with normally fed control rats.

Visceral Adipose Tissue Inflammatory Factors (TNF-Alpha, SOCS3) in Gestational Diabetes (GDM): Epigenetics as a Clue in GDM Pathophysiology.

Gestational diabetes (GDM) is among the most challenging diseases in westernized countries, affecting mother and child, immediately and in later life. Obesity is a major risk factor for GDM. However, the impact visceral obesity and related epigenetics play for GDM etiopathogenesis have hardly been considered so far.

Sex-specific epigenetic alterations of the hypothalamic Agrp-Pomc system do not explain 'diabesity' in the offspring of high-fat diet (HFD) overfed maternal rats.

Maternal high-fat diet (HFD) overfeeding pre- and during pregnancy and lactation may 'program' a 'diabesity' predisposition in the offspring, for inconclusive reasons. Acquired alterations of the hypothalamic promoter methylation and mRNA expression of the satiety neurohormone Pomc are possibly of critical importance here. We investigated within one developmental approach, including male and female rats, the sex-specific DNA methylation pattern and corresponding mRNA expression of both Pomc and its endogenous functional antagonist Agrp in the hypothalamus of adult HFD offspring.

Visceral adipose tissue alteration of expression is associated with gestational diabetes but not promoter DNA methylation.

Obesity and diabetes are at an epidemic rate, as well as growing incidences of gestational diabetes mellitus (GDM) which causes pregnancy risks, and harm in both maternal and child health. It remains unclear which molecular mechanisms are driving the functional differences between visceral and subcutaneous fat and how these types directly affect an individual's health outcome. Paired abdominal subcutaneous and omental visceral adipose tissue were collected from women with GDM (n = 20) and with normal glucose tolerance (NGT, n = 22) during planned caesarian section.

Hypothalamic insulin receptor expression and DNA promoter methylation are sex-specifically altered in adult offspring of high-fat diet (HFD)-overfed mother rats.

Maternal overnutrition around reproduction has been shown to increase the offspring's risk for "diabesity," mediated by altered hypothalamic neuropeptide expression. In this report, a possible contribution of altered hypothalamic sensing capacity for the peripheral satiety signals glucose, insulin and leptin will be addressed, taking into account potential sex differences. Specifically, we evaluated the effects a maternal high-fat diet (HFD) overfeeding has in rats pre- and during pregnancy and lactation on the hypothalamic gene expression patterns of insulin and leptin receptors (InsR, ObRb) and glucose transporter 3 (Glut3) as well as DNA methylation in the offspring at adult age (day 200 of life).

Alterations of adiponectin gene expression and DNA methylation in adipose tissues and blood cells are associated with gestational diabetes and neonatal outcome.

Background: Adiponectin critically contributes to metabolic homeostasis, especially by insulin-sensitizing action. Gestational diabetes mellitus (GDM) is characterized by insulin resistance leading to materno-fetal hyperglycemia and detrimental birth outcomes. By investigating paired subcutaneous (SAT) and visceral adipose tissue (VAT) as well as blood (cell) samples of GDM-affected (n = 25) vs.

Reduced Insulin Receptor Expression and Altered DNA Methylation in Fat Tissues and Blood of Women With GDM and Offspring.

Context: Altered expression of the insulin receptor (IR) in adipose tissue (AT) could contribute to gestational diabetes mellitus (GDM) etiopathogenesis. Transcriptional regulation via epigenetic mechanisms (e.g.

Maternal overweight is not an independent risk factor for increased birth weight, leptin and insulin in newborns of gestational diabetic women: observations from the prospective 'EaCH' cohort study.

Background: Both gestational diabetes mellitus (GDM) as well as overweight/obesity during pregnancy are risk factors for detrimental anthropometric and hormonal neonatal outcomes, identified to 'program' adverse health predispositions later on. While overweight/obesity are major determinants of GDM, independent effects on critical birth outcomes remain unclear. Thus, the aim of the present study was to evaluate, in women with GDM, the relative/independent impact of overweight/obesity vs.

Short-term regulation of the hypothalamic melanocortinergic system under fasting and defined glucose-refeeding conditions in rats: a laser capture microdissection (LMD)-based study.

It is well established that under fasting conditions the expression of the orexigenic neuropeptide agouti-related peptide (AGRP) is up-regulated in the hypothalamic arcuate nucleus (ARC), while inconsistent data exist regarding fasting regulation of the anorexigenic neurohormone proopiomelanocortin (POMC). Inconsistencies might have methodological reasons, especially concerning neuromorphological and/or experimental (nutritional) specificity. We analyzed the expression of both neuropeptides in ARC neurons, using lasercapture microdissection (LMD) and real-time PCR in 12h fasted vs.

Epigenetic malprogramming of the insulin receptor promoter due to developmental overfeeding.

Aim: Prenatal and neonatal overfeeding programs a permanent obesity and diabetes disposition, e.g., due to induction of hypothalamic insulin resistance.

Hypothalamic proopiomelanocortin promoter methylation becomes altered by early overfeeding: an epigenetic model of obesity and the metabolic syndrome.

Pre- and neonatal overfeeding programmes a permanent obesity disposition and accompanying diabetic and cardiovascular disorders, by unknown mechanisms. We proposed that early overfeeding may alter DNA methylation patterns of hypothalamic promoter regions of genes critically involved in the lifelong regulation of food intake and body weight. We induced neonatal overfeeding by rearing Wistar rats in small litters (SL) and thereafter mapped the DNA methylation status of CpG dinucleotides of gene promoters from hypothalamic tissue, using bisulfite sequencing.

'Programming' of orexigenic and anorexigenic hypothalamic neurons in offspring of treated and untreated diabetic mother rats.

Exposure to maternal diabetes in utero (GD) may 'program' for obesity. Orexigenic neuropeptides, like neuropeptide Y (NPY) and agouti-related peptide (AGRP), and anorexigenic neuropeptides, like proopiomelanocortin (POMC) and alpha-melanocyte-stimulating hormone (MSH), are decisively involved in body weight regulation. We investigated consequences of GD and its treatment by pancreatic islet transplantation in rats for development of neuropeptidergic neurons in the arcuate hypothalamic nucleus (ARC) in weanling offspring.

Cross-fostering to diabetic rat dams affects early development of mediobasal hypothalamic nuclei regulating food intake, body weight, and metabolism.

Exposure to maternal gestational diabetes (GD) "programs" offspring for obesity in childhood and later life. Recent clinical data suggest that neonatal ingestion of breast milk from diabetic mothers might be crucially involved. Mediobasal hypothalamic nuclei such as the ventromedial nucleus (VMN), the paraventricular nucleus (PVN) and the arcuate nucleus (ARC) play a key role in the central nervous system regulation of food intake and body weight.