Physiological and pathological evidence of O-GlcNAcylation regulation during pregnancy related process.

O-GlcNAcylation is a dynamic and reversible post-translational modification (PTM) controlled by the enzymes O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). Changes in its expression lead to a breakdown in cellular homeostasis, which is linked to several pathological processes. Placentation and embryonic development are periods of high cell activity, and imbalances in cell signaling pathways can result in infertility, miscarriage, or pregnancy complications. O-GlcNAcylation is involved in cellular processes such as genome maintenance, epigenetic regulation, protein synthesis/degradation, metabolic pathways, signaling pathways, apoptosis, and stress response. Trophoblastic differentiation/invasion and placental vasculogenesis, as well as zygote viability and embryonic neuronal development, are all dependent on O-GlcNAcylation. This PTM is required for pluripotency, which is a required condition for embryonic development. Further, this pathway is a nutritional sensor and cell stress marker, which is primarily measured by the OGT enzyme and its product, protein O-GlcNAcylation. Yet, this post-translational modification is enrolled in metabolic and cardiovascular adaptations during pregnancy. Finally, evidence of how O-GlcNAc impacts pregnancy during pathological conditions such as hyperglycemia, gestational diabetes, hypertension, and stress disorders are reviewed. Considering this scenario, progress in understanding the role of O- GlcNAcylation in pregnancy is required.

Preeclampsia association of placental nucleotide variations in eNOS, VEGFA, and FLT-1 genes in Latin American pregnant women.

INTRODUCTION: Preeclampsia is a leading cause of maternal and fetal morbidity in low- and middle-income countries, including those in Latin America. Placental vascular alterations are crucial in the pathophysiology of preeclampsia and few studies have evaluated nucleotide variations on genes associated with vascular regulation in the human placenta. This study aimed to evaluate whether placental nucleotide variations on eNOS, VEGFA, and FLT-1 genes are more frequently associated with preeclampsia in the Latin American population. METHODS: This case-control study included placental tissue from 88 controls and 82 cases that were genotyped through Taqman probes for eNOS, VEGFA, and FLT-1 genes. The intergroup comparisons were analyzed with the Mann-Whitney U test. Genotype and allele frequencies were compared by the X2 test. The association between the nucleotide variants with preeclampsia was evaluated through logistic regression analysis. RESULTS: A significant association was observed for VEGFA SNV rs2010963 (OR 1.95; CI 95% 1.13-3.37), after adjusting for population substructure. The allele combination T, G, G, C, C, C (rs2070744, rs1799983, rs2010963, rs3025039, rs699947 and rs4769613 respectively), showed a negative association with preeclampsia (OR 0.08; CI 95% 0.01-0.93). DISCUSSION: Placental SNV rs2010963 in the VEGFA gene was a risk factor for preeclampsia, while the allele combination T, G, G, C, C, C may represent potential protective factors for preeclampsia within Latin American women.

Maternal and Fetal-Placental Effects of Etanercept Treatment During Rats' Pregnancy.

Etanercept is a tumor necrosis factor alpha (TNF-α) inhibitor chronically used to treat autoimmune diseases. However, the use of etanercept during pregnancy still needs to be further investigated. The aim of this study is to evaluate the etanercept treatment during pregnancy, analyzing maternal reproductive performance, fetal outcomes, and placental repercussions. Wistar rats (200-250 g) were mated and randomly distributed into two experimental groups: control and etanercept (n = 10 animals/group). Treatments with etanercept (0.8 mg/kg, s.c.), or saline (control group) were carried out on days 0, 6, 12, and 18 of gestation. On the morning of the 21st day of pregnancy, rats were euthanized in a CO2 chamber and submitted to laparotomy to remove the fetuses, placentas, ovaries, and maternal organs. There were no differences between groups in the following parameters: water and food consumption; placental efficiency; reproductive parameters, including number of corpora lutea and implants, reabsorption, and pre- and post-implantation losses. However, etanercept treatment increased liver weight, reduced fetal and placental weight, decreased the placental junction zone, reduced the percentage of normal fetuses, and increased visceral or skeletal fetal abnormalities. Therefore, etanercept resulted in damages more related to fetus and placenta. However, more studies with different doses are required to better predict possible injuries elicited using etanercept during pregnancy.

Evaluation of drug prescriptions for pregnant women in the Legal Amazon Region / Avaliação de prescrições medicamentosas para gestantes da Amazônia Legal

Abstract Objectives: to evaluate the drug prescriptions for pregnant women in the Legal Amazon during prenatal care. Methods: this is a pharmacoepidemiological, descriptive, retrospective and cross-sectional study. Medical records included sociodemographic variables, prenatal care, most frequent pharmacological classes prescribed, risk classification of drugs and possible drug-drug interactions among pregnant women. Results: a total of 159 records from pregnant women, enrolled in the Unified Health System were used. Most pregnant women began prenatal consultations in the first trimester of pregnancy (53.3%) whereas most of the drugs were prescribed in the second gestational trimester (55.5%). The most used pharmacological classes, classified according to the National List of Essential Drugs were: antianemic preparations (52.9%), vitamins (12.5%) and analgesic (10.6%). According to the risk classification, the highest prevalence of prescribed drugs belongs to category A (46.8%), followed by category C (28.9%), category B (20.0%) and category D (4.3%). Eight possible drug-drug interactions were found, being considered with mild severity, and six classified with moderate risk. Conclusions: the results demonstrate a lack of information regarding prescription drugs for pregnant women and this may endanger maternal and fetal health. It is essential that medical records be an effective therapeutic tool, which should be read, analyzed and reviewed in order to ensure effective and safe medical treatment.

Resumo Objetivos: avaliar a prescrição de medicamentos para gestantes da Amazônia Legal, durante o pré-natal. Métodos: trata-se de um estudo farmacoepidemiológico, descritivo, retrospectivo e transversal. Através de prontuários médicos foram avaliados variáveis sociodemográficas, assistência pré-natal, classes farmacológicas mais prescritas, classificações de risco e possíveis interações medicamentosas nas gestantes. Resultados: foram utilizados 159 prontuários de gestantes usuárias do Sistema Único de Saúde. A maioria das grávidas iniciaram as consultas do pré-natal no primeiro trimestre gestacional (53,3%) e a maior parte dos medicamentos prescritos foram no segundo trimestre gestacional (55,5%). As classes mais utilizadas conforme a Relação Nacional de Medicamentos Essenciais foram: preparações antianêmicas (52,9%), vitaminas (12,5%) e analgésico (10,6%). De acordo com a classificação de risco, a prevalência maior dos medicamentos prescritos pertence à categoria A de risco (46,8%), seguido da categoria C (28,9%), categoria B (20,0%) e categoria D (4,3%). Foram encontradas oito possíveis interações medicamentosas, sendo duas consideradas de risco leve e seis de risco moderado. Conclusões: os resultados demonstram falhas na prescrição de medicamentos para gestantes o que pode colocar em risco a saúde materna e fetal. É fundamental que o prontuário médico seja uma ferramenta terapêutica efetiva, o qual deve ser lido, analisado e revisado a fim de garantir um tratamento medicamentoso eficaz e seguro.