Fulvio Zullo

Genome–wide microRNA expression profiling in placentas from pregnant women exposed to BPA

BackgroundBisphenol A (BPA) is an environmental compounds is known to possess endocrine disruption potentials. Bisphenol A has epigenetic effects as deregulated expression of microRNAs; such epigenetic marks can induce up/down alterations in gene expression that may persist throughout a lifetime. Bisphenol A (BPA) exposure has been documented in pregnant women, but consequences for development of offspring after BPA exposure during pregnancy are not yet widely studied. Therefore, the aim of this study was to gain a comprehensive understanding of microRNAs changes in the placenta transcriptome from pregnant women subjected to therapeutic abortion for fetal malformation and correlate the impact of gestational exposure to BPA on these developmental changes.MethodsWe performed a comparative analysis of genome wide miRNA expression in placentas from pregnant women exposed to BPA using microarray technology to identify miRNAs which were aberrantly expressed in placentas from malformed fetuses. The expression changes of differential expressed miRNAs in the samples used for microarray were confirmed by qPCR . Beside, we applied various bioinformatics tools to predict the target genes of the identified miR-146a and explore their biological function and downstream pathways.ResultsWe found that miR-146a was significant overexpressed and correlated significantly with BPA accumulation in the placenta from pregnant women living in a polluted area and undergoing therapeutic abortion due to fetal malformations. Beside, we applied various bioinformatics tools to predict the target genes of miR-146a and explore their biological function and downstream pathways.ConclusionsFor the first time, we found, in humans, that miR-146a was significant over-expressed and correlated significantly with BPA accumulation in the placenta. Our results lead to the suggestion that miRNAs could be potential biomarkers to clarify the mechanisms of environmental diseases.

Bisphenol A and congenital developmental defects in humans.

Over 50% of the causes of fetal malformations in humans are still unknown. Recent evidence suggests the relationship between environmental exposure to endocrine disruptors and fetal malformations. Our study aims to establish the role of Bisphenol A (BPA), if any, in altering human reproduction. We enrolled 151 pregnant women who were divided into two groups: case group (CS, n=101), women with established diagnosis of developmental defect, and control group (CL, n=50), pregnant women with normally developed fetus. Total, free and conjugated BPA were measured in their blood using GC-MS with isotopic dilution. The results show a correlation between environmental exposure to BPA and the genesis of fetal malformations. Conjugated BPA, which was higher in the CL, casts light on the hypothesis that a reduced ability to metabolize the chemical in the mother can concur to the occurrence of malformation. In a more detailed manner, in case of chromosomal malformations, the average value of free BPA appears to be nearly three times greater than that of the controls. Similarly, in case of central and peripheral nervous system non-chromosomal malformations, the value of free BPA is nearly two times greater than that of the controls.

Pharmacological approach to overactive bladder and urge urinary incontinence in women: an overview

Besides life-style changes, electrical stimulation or surgery, pharmacological treatment is becoming the first-choice approach in women suffering from lower urinary tract symptoms (LUTS), including urge urinary incontinence (UUI) and overactive bladder (OAB). Several drugs for the treatment of bladder storage and voiding disorders are currently available and, in the near future, novel compounds with higher specificity for the lower urinary tract receptors will be accessible. This will bring optimization of therapy, reducing side effects and increasing compliance, especially in patients with comorbidities and in women. The purpose of this paper is to give an overview on the pharmacotherapy of two common inter-correlated urological conditions, UUI and OAB. The study was conducted by analyzing and comparing the data of the recent international literature on this topic. Advances in the discovery of pharmacological options have dramatically improved the quality of life of patients affected by incontinence, but further studies are needed to increase the effectiveness and safety of the therapies used in this field.

Association between exposure to dioxin-like polychlorinated biphenyls and miR-191 expression in human peripheral blood mononuclear cells

Accumulating evidence shows an association between deregulation of miRNAs and exposure to environmental chemicals; miRNAs play a unique regulatory role in gene expression. Among environmental pollutants, dioxins are a family of compounds that are known to have multiple hazardous effects. Also, in utero exposure of the fetus to dioxins has been shown to cause impaired psychomotor development, decreased immune function and skin disease. miR-191 is a microRNA that has been found to be up-regulated by dioxin in hepatocellular carcinoma cells in vitro. Our study provides the first molecular evidence in vivo of a positive relationship between levels of polychlorinated biphenyls (PCBs) and miR-191 expression in human peripheral blood mononuclear cells. miR-191 expression was significantly correlated with blood concentrations of total PCB and, in particular, of 3,3,4,4,5,5-hexachlorobiphenyl (PCB 169, a coplanar congener). Blood concentrations of PCB 169 correlated significantly with miR-191 expression in pregnant women living in a PCB-polluted area, who underwent therapeutic abortion due to fetal malformations. These data suggest that miRNAs could be potential biomarkers to clarify the mechanisms of environmental disease.

BAG3 Protein Is Over-Expressed in Endometrioid Endometrial Adenocarcinomas

Endometrioid endometrial cancer is the most common gynaecological tumor in developed countries, and its incidence is increasing. The definition of subtypes, based on clinical and endocrine features or on histopathological characteristics, correlate to some extent with patients prognosis, but there is substantial heterogeneity within tumor types. The search for molecules and mechanisms implied in determining the progression and the response to therapy for this cancer is still ongoing. BAG3 protein, a member of BAG family of co‐chaperones, has a pro‐survival role in several tumor types. BAG3 anti‐apoptotic properties rely on its characteristic to bind several intracellular partners, thereby, modulating crucial events such as apoptosis, differentiation, cell motility, and autophagy. BAG3 expression in human endometrial cancer tissues was not investigated so far. Here, we show that BAG3 protein levels are elevated in tumoral and hyperplastic cells in respect to normal glands. Furthermore, BAG3 subcellular localization appears to be changed in tumoral compared to normal cells. Our results indicate a possible role for BAG3 protein in the maintenance of cell survival in endometrioid endometrial cancer and suggest that this field of studies is worthy of further investigations. J. Cell. Physiol. 232: 309–311, 2017.

Ultrasonographic evaluation of urethrovesical junction mobility: correlation with type of delivery and stress urinary incontinence

Introduction and hypothesisA relationship between urinary incontinence and hypermobility of the urethrovesical junction (UVJ) during pregnancy has been described. The aim of the study was to compare the effects of vaginal delivery (VD) and caesarean section (CS) on UVJ mobility.MethodsThe retrovesical angle (RVA) and the anterior angle between the UVJ and the pubic bone, the pubovesical angle (PVA), were evaluated ultrasonographically in controls and pregnant women during their first pregnancy between 38 and 40xa0weeks, and then re-evaluated 6xa0weeks and 6xa0months after delivery. All patients completed a validated questionnaire (ICIQ-SF). Differences between and within groups were assessed with Student’s t test, the chi-squared test for trend, and one-way two-tailed analysis of variance with Scheffé’s post-hoc test. The correlation between PVA and RVA was evaluated using the Spearman R correlation. The positive predictive value, negative predictive value, sensitivity and specificity for the prediction of stress urinary incontinence (SUI) symptoms were also determined.ResultsIncluded in the study were 42 controls and 217 pregnant women. PVA at rest, during cough and Valsalva manoeuvre was significantly higher in pregnant women than in controls and in women 6xa0weeks after VD in comparison with women who had undergone CS. Patients affected by SUI showed a significantly higher PVA. RVA did not differ between subjects affected or not by SUI symptoms. PVA and RVA were not correlated with each other.ConclusionsPVA and RVA are increased in pregnant women in comparison with controls. In patients undergoing VD, PVA is restored significantly later than in those undergoing CS. The change in RVA after pregnancy and delivery seems to persist longer than the change in PVA.

A rare case of endometriosis in Turner's syndrome

Endometriosis is defined by the presence of functional endometrial tissue outside the uterine cavity and musculature. It has a prevalence rate as high as 35e50% in women experiencing pain or infertility [1] and sometimes has a peculiar and rare onset [2,3]. Endometriosis is a common disease in menstruating women [4,5] but has also been reported in postmenopausal or surgically castrated women on hormone replacement therapy (HRT) [6]. The common denominator of all such cases is exposure to female hormones [7]. However, endometriosis, a common and important clinical problem in women of reproductive age, has rarely been described in prepubertal girls. In patients with Turners syndrome or other ovarian dysgenesis, endometriosis is very rare. Some cases are subclinical, and endometriosis is an incidental finding during routine examination. Although endometriosis was described in the medical literature at the end of the 19th century, and the first theories regarding its hystogenesis were developed at the beginning of the 20th century, the real pathogenesis of endometriosis remains unknown. Most studies about the etiology of endometriosis claim that the main possible causes of endometriosis are probably multifactorial. Three theories of histogenesis have been proposed. (1) The metastatic theory [8] proposes the transplantation of endometrial tissue via retrograde menstrual implantation, vascular/lymphatic spread, and intraoperative implantation. (2) The coelomic metaplastic theory [9] suggests that the germinal epithelium of the ovary can be transformed by metaplasia into endometrium. This theory, which initially explained only ovarian endometriosis, has since been extended to the peritoneal serosa, as embryologic studies have indicated that Mullerian ducts, the