Bárbara Yasmin Gueuvoghlanian-Silva

Genetic Polymorphisms and Recurrent Spontaneous Abortions: An Overview of Current Knowledge

The relevance of gene polymorphisms in the development of unexplained recurrent spontaneous abortion is still unclear. Cytokines, angiogenic mediators, and hormones are involved in all stages of reproduction and pregnancy outcome. Impaired production and/or unbalanced ratios of these mediators have been implicated in the pathogenesis of unexplained recurrent spontaneous abortion. Functional polymorphism influence gene activity and therefore can interfere with the expression of mediators. Several studies have been carried out to evaluate the relationship between cytokines, angiogenic mediators, and hormones gene polymorphisms and unexplained recurrent spontaneous abortion. The results of these studies are mostly contradictory, and few significant associations have been identified. Up to present time, the evidence is insufficient to support the evaluation of cytokines, angiogenic mediators, and hormones gene polymorphism in routine workup in all cases of recurrent pregnancy loss, and these tests are not included in any of the major obstetric guidelines.

Cytokine Levels in Gestational Diabetes Mellitus: a Systematic Review of the Literature

Gestational diabetes mellitus (GDM) is an inflammatory condition that involves unbalanced cytokine production. We carried out a systematic review on the relationship between GDM and maternal circulating levels of cytokines in the 2nd/3rd trimesters.

Profile of inflammatory mediators in gestational diabetes mellitus: phenotype and genotype.

Citation Gueuvoghlanian‐Silva BY, Torloni MR, Mattar R, de Oliveira LS, Scomparini FB, Nakamura MU, Daher S. Profile of inflammatory mediators in gestational diabetes mellitus: phenotype and genotype. Am J Reprod Immunol 2012; 67: 241–250

Resistin concentration and gestational diabetes: a systematic review of the literature

Gestational diabetes (GD) exposes mothers and infants to the risk of immediate and later adverse outcomes. Increased insulin resistance is a common feature of GD and obesity. Because of its critical role in regulating insulin sensitivity, resistin has been implicated in the physiopathology of GD. The aim of this study was to review the existing literature on the relationship between circulating maternal resistin levels and GD. Three electronic databases (MEDLINE, EMBASE, and LILACS) were searched for pertinent studies published from 2001 to 2012, without language restrictions. Eleven studies, with a total of 639 participants between 23 and 41 weeks of gestation, were included. The number of GD patients per study ranged from 11 to 81, with varying degrees of disease severity and several different GD diagnostic criteria. Mean concentrations of resistin varied widely both in control women (0.05-22.21 ng/ml) and in GD patients (0.05-62.38 ng/ml). We performed a meta-analysis including a total of 10 studies, and also subgroup analyses according to gestational age at sample collection (up to 32 and >33 weeks). The pooled absolute mean difference (WMD) in resistin levels was slightly lower in GD patients than in controls, but this did not reach statistical significance (WMD=-0.02, 95% CI -0.07 to 0.04). According to the data from the 11 studies analyzed, there was no association between circulating resistin levels and GD. However, this result should be interpreted with caution owing to the large heterogeneity amongst the existing published studies.

Angiogenic factors and uterine Doppler velocimetry in early- and late-onset preeclampsia

To assess correlations between maternal serum levels of pro‐ and anti‐angiogenic factors with uterine perfusion in women with early‐ compared with late‐onset preeclampsia, and in healthy pregnant women.

FAS and FAS-L genotype and expression in patients with recurrent pregnancy loss.

We assessed FAS and FAS-L gene polymorphisms and messenger RNA (mRNA) levels in patients with recurrent pregnancy loss (RPL). This case–control study compared 129 women with RPL with 235 healthy multiparous women (control group). Genomic DNA and total mRNA were extracted from whole blood, and polymorphisms genotyping was performed by polymerase chain reaction (PCR). Messenger RNA expression levels were analyzed by real-time PCR. Data were analyzed by chi-square and Fisher exact tests; P < .05 was considered significant. There were no significant differences in the FAS (670 A/G) genotype or allelic frequencies between the RPL and control groups. We found significant differences in the FAS-L (844 C/T) genotype and allelic frequencies between women with RPL and controls. Patients with RPL had significantly higher FAS-L expression. Our data suggest that FAS-L gene polymorphism is associated with increased susceptibility to RPL. Moreover, women with RPL seem to abnormally express FAS-FAS-L molecules.

Getting too sweet: galectin-1 dysregulation in gestational diabetes mellitus

Galectin-1 (gal-1) is a prototype carbohydrate-binding protein, whose dysregulation is associated with adverse pregnancy outcomes such as spontaneous abortion and pre-eclampsia. Furthermore, it is known that faulty gal-1 protein production or gene regulation can be caused by single-nucleotide polymorphisms in the LGALS1 gene. Gestational diabetes mellitus (GDM) is also an adverse pregnancy outcome and the most common metabolic disorder during gestation. However, gal-1 expression patterns during GDM remain largely unknown. Our aims were to define local and peripheral gal-1 expression patterns during pregnancy, and to investigate LGALS1 gene polymorphisms in GDM patients. Circulating gal-1 levels were determined by ELISA in GDM patients and normal pregnant controls, and LGALS1 gene polymorphisms were assessed for association with GDM. Placental tissues were collected from control and GDM term pregnancies to evaluate local gal-1 expression by immunofluorescence. Our results show that GDM is associated with a failure to increase circulating gal-1 levels during the second and third trimester, as well as overexpression of gal-1 in placental tissue. Additionally, the LGALS1 polymorphism rs4820294 was associated with the development of GDM. In pregnancies complicated by GDM, we observed gal-1 dysregulation both locally in the placenta and peripherally in the circulation. Furthermore, the association between the LGALS1 polymorphism and GDM may indicate a genetic contribution to this adverse pregnancy outcome.

Inflammatory mediator gene polymorphisms and gestational diabetes: a review of the literature.

The incidence of gestational diabetes (GD) is rising worldwide, in parallel with obesity and type 2 diabetes. Obesity and GD are conditions that have in common a state of chronic, low-grade subclinical inflammation characterized by abnormal production of cytokines and mediators. Genetic polymorphisms may influence the production of inflammatory mediators and predispose to different disorders, including diabetes. The aim of this study was to review the existing literature on the relationship between inflammatory mediator gene polymorphisms and GD. The search in PubMed was restricted to articles published in English, from January 1990 to December 2010. Eight studies were included. These publications evaluated 13 different SNPs and six inflammatory mediators in the blood of women with GD. Gene polymorphisms related to leptin, mannose-binding lectin (MBL) and RAGE (receptor for advanced glycation end products) were individually evaluated in a single study each. Leptin and MBL plasma levels were also evaluated in two studies. The participants included in the studies were ethnically different, but matched with controls. Different criteria were adopted to select the participants. Seven of the eight studies included took into consideration the BMI of patients and controls. Due to the heterogeneity and limited number of studies on GD and inflammatory gene polymorphisms, we could not pool together any of the results or perform any additional analyses of the existing data. Since the existing findings come from isolated studies with mostly small sample sizes, there is a need for new, larger, properly designed studies of good methodological quality.

Treg and NK cells related cytokines are associated with deep rectosigmoid endometriosis and clinical symptoms related to the disease

The aim of this study was to evaluate Treg and NK cells related cytokines in deep infiltrating endometriosis lesions and its relationship with clinical symptoms of the disease. mRNA expression of Transforming Growth Factor Beta (TGFB), Interleukin (IL)10, Interferon Gamma (IFNG), IL7, and IL15 was analyzed by Real-Time PCR in eutopic endometrium and rectosigmoid lesions from 11 women with deep infiltrating endometriosis and in eutopic endometrium from 11 healthy women. IL10, IFNG, and IL7 expression was significantly higher in endometriotic bowel lesions than in eutopic endometrium from women with endometriosis. IL10 and TGFB expression was significantly higher in endometriotic bowel lesions than in eutopic endometrium from healthy women. In addition, TGFB and IL15 levels correlated positively with deep dyspareunia and cyclic dyschezia, respectively, while IL7 levels correlated negatively with dysmenorrhea. Deep infiltrating rectosigmoid endometriosis displays alterations in Treg and NK cells related cytokine, and TGFB, IL7 and IL15 expression is related with dyspareunia, dysmenorrhea and cyclic dyschezia, respectively, in patients with the disease.

Corrigendum to “What do we know about regulatory T cells and endometriosis? A systematic review” [J. Reprod. Immunol. 120 (April) (2017) 48–55]

Noteworthy is the lead author and year, methodological design, method of analysis of samples and results found, showing increase (↑), decrease (↓) or no difference (=) in TReg cells concentrations in eutopic endometrium, endometriotic lesions, peritoneal fluid and peripheral blood of research subjects with endometriosis and the non-endometriosis controls. The symbol (−) indicates that the tissue/fluid was not evaluated. a Studies with Bona Fide TReg cells (CD4CD25FoxP3 TReg cells phenotypes). b Studies with Sub-optimal TReg cells (CD4CD25 TReg phenotypes or FoxP3 expression). c The authors did not find any significance difference between the menstrual cycle phases. d Control versus Endometriosis. e Versus eutopic endometrium from women with endometriosis and/or the non-endometriosis controls.