RESUMO
Multiple sclerosis (MS) is a common disease in young women of reproductive age, characterized by demyelination of the central nervous system (CNS). Understanding how genes related to MS are expressed during pregnancy can provide insights into the potential mechanisms by which pregnancy affects the course of this disease. This review article presents evidence-based studies on these patients' gene expression patterns. In addition, it constructs interaction networks using bioinformatics tools, such as STRING and KEGG pathways, to understand the molecular role of each of these genes. Bioinformatics research identified 25 genes and 21 signaling pathways, which allows us to understand pregnancy patients' genetic and biological phenomena and formulate new questions about MS during pregnancy.
Assuntos
Biologia Computacional , Esclerose Múltipla , Humanos , Esclerose Múltipla/genética , Esclerose Múltipla/metabolismo , Feminino , Gravidez , Biologia Computacional/métodos , Redes Reguladoras de Genes , Complicações na Gravidez/genética , Complicações na Gravidez/metabolismo , Perfilação da Expressão Gênica , Transdução de Sinais/genética , Regulação da Expressão GênicaRESUMO
Using a rabbit model, we investigated whether maternal intake of a high-fat and high-carbohydrate diet (HFCD) before and during pregnancy induces an increase in micronuclei frequency and oxidative stress in offspring during adulthood. Female rabbits received a standard diet (SD) or HFCD for two months before mating and during gestation. The offspring from both groups were nursed by foster mothers fed SD until postnatal day 35. After weaning, all the animals received SD until postnatal day 440. At postnatal day 370, the frequency of micronuclei in peripheral blood reticulocytes (MN-RETs) increased in the male offspring from HFCD-fed mothers compared with the male offspring from SD-fed mothers. Additionally, fasting serum glucose increased in the offspring from HFCD-fed mothers compared with the offspring from SD-fed mothers. At postnatal day 440, the offspring rabbits were challenged with HFCD or continued with SD for 30 days. There was an increase in MN-RET frequency in the male rabbits from HFCD-fed mothers, independent of the type of challenging diet consumed during adulthood. The challenge induced changes in serum cholesterol, LDL and HDL that were influenced by the maternal diet and offspring sex. We measured malondialdehyde in the liver of rabbits as an oxidative stress marker after diet challenge. Oxidative stress in the liver only increased in the female offspring from HFCD-fed mothers who were also challenged with this same diet. The data indicate that maternal overnutrition before and during pregnancy is able to promote different effects depending on the sex of the animals, with chromosomal instability in male offspring and oxidative stress and hypercholesterolemia in female offspring. Our data might be important in the understanding of chronic diseases that develop in adulthood due to in utero exposure to maternal diet.
Assuntos
Dano ao DNA , Hipernutrição/genética , Efeitos Tardios da Exposição Pré-Natal/genética , Animais , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Feminino , Masculino , Fenômenos Fisiológicos da Nutrição Materna , Hipernutrição/complicações , Hipernutrição/patologia , Estresse Oxidativo/fisiologia , Gravidez , Complicações na Gravidez/genética , Complicações na Gravidez/patologia , Efeitos Tardios da Exposição Pré-Natal/patologia , Coelhos , Caracteres SexuaisRESUMO
OBJECTIVES: To investigate the association between selected single nucleotide polymorphisms (SNPs) with cervical insufficiency and its relationship with obstetric history. METHODS: Twenty-eight women with cervical insufficiency (case group) and 29 non-pregnant women (control group) were included. The SNPs sequenced included rs2586490 in collagen type I alpha 1 chain (COL1A1), rs1882435 in collagen type IV alpha 3 chain (COL4A3), rs2277698 in metallopeptidase inhibitor 2 (TIMP2), and rs1800468 in transforming growth factor beta 1 (TGFB1). RESULTS: We found a higher frequency of the normal allele in the control group (65.5%) and the homozygous mutated genotype in the case group (64.3%) for rs2586490 in COL1A1 (p=0.023). An unplanned finding in the cervical insufficiency group was a higher gestational age of delivery (median≥38 weeks) in the mutated allele than in the wild-type genotype (median of 28.2 weeks) for rs2857396, which is also in the COL1A1 gene (p=0.011). CONCLUSIONS: The findings of the present study corroborate the hypothesis that cervical insufficiency has a genetic component and probably involves genes encoding proteins in the extracellular matrix, in addition to inflammatory processes.
Assuntos
Colágeno Tipo I/genética , Complicações na Gravidez , Incompetência do Colo do Útero , Adulto , Brasil/epidemiologia , Estudos de Casos e Controles , Cadeia alfa 1 do Colágeno Tipo I , Proteínas da Matriz Extracelular/genética , Feminino , Predisposição Genética para Doença , Idade Gestacional , Humanos , Polimorfismo de Nucleotídeo Único , Gravidez , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/epidemiologia , Complicações na Gravidez/genética , Resultado da Gravidez/epidemiologia , História Reprodutiva , Incompetência do Colo do Útero/diagnóstico , Incompetência do Colo do Útero/epidemiologia , Incompetência do Colo do Útero/genéticaAssuntos
Síndrome do Ovário Policístico/fisiopatologia , Complicações na Gravidez/fisiopatologia , Efeitos Tardios da Exposição Pré-Natal/etiologia , Androgênios/metabolismo , Transtorno do Espectro Autista/etiologia , Biomarcadores/metabolismo , Doenças Cardiovasculares/etiologia , Feminino , Microbioma Gastrointestinal , Predisposição Genética para Doença , Genitália/embriologia , Genitália/fisiopatologia , Transtornos do Crescimento/etiologia , Desenvolvimento Humano/fisiologia , Humanos , Doenças Metabólicas/etiologia , Síndrome do Ovário Policístico/genética , Síndrome do Ovário Policístico/metabolismo , Gravidez , Complicações na Gravidez/genética , Complicações na Gravidez/metabolismo , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Efeitos Tardios da Exposição Pré-Natal/fisiopatologiaRESUMO
Recent revolutionary advances at the intersection of medicine, omics, data sciences, computing, epidemiology, and related technologies inspire us to ponder their impact on health. Their potential impact is particularly germane to the biology of pregnancy and perinatal medicine, where limited improvement in health outcomes for women and children has remained a global challenge. We assembled a group of experts to establish a Pregnancy Think Tank to discuss a broad spectrum of major gestational disorders and adverse pregnancy outcomes that affect maternal-infant lifelong health and should serve as targets for leveraging the many recent advances. This report reflects avenues for future effects that hold great potential in 3 major areas: developmental genomics, including the application of methodologies designed to bridge genotypes, physiology, and diseases, addressing vexing questions in early human development; gestational physiology, from immune tolerance to growth and the timing of parturition; and personalized and population medicine, focusing on amalgamating health record data and deep phenotypes to create broad knowledge that can be integrated into healthcare systems and drive discovery to address pregnancy-related disease and promote general health. We propose a series of questions reflecting development, systems biology, diseases, clinical approaches and tools, and population health, and a call for scientific action. Clearly, transdisciplinary science must advance and accelerate to address adverse pregnancy outcomes. Disciplines not traditionally involved in the reproductive sciences, such as computer science, engineering, mathematics, and pharmacology, should be engaged at the study design phase to optimize the information gathered and to identify and further evaluate potentially actionable therapeutic targets. Information sources should include noninvasive personalized sensors and monitors, alongside instructive "liquid biopsies" for noninvasive pregnancy assessment. Future research should also address the diversity of human cohorts in terms of geography, racial and ethnic distributions, and social and health disparities. Modern technologies, for both data-gathering and data-analyzing, make this possible at a scale that was previously unachievable. Finally, the psychosocial and economic environment in which pregnancy takes place must be considered to promote the health and wellness of communities worldwide.
Assuntos
Promoção da Saúde/tendências , Resultado da Gravidez , Economia , Feminino , Desenvolvimento Fetal/genética , Desenvolvimento Fetal/fisiologia , Humanos , Assistência Perinatal , Gravidez , Complicações na Gravidez/etnologia , Complicações na Gravidez/genética , Complicações na Gravidez/fisiopatologia , Resultado da Gravidez/epidemiologia , Resultado da Gravidez/genética , PsicologiaRESUMO
OBJECTIVE: To report the case of a patient with mosaic Turner syndrome who underwent assisted reproduction treatment with preimplantation genetic testing for aneuploidy and gave birth to a healthy baby girl with normal karyotype; and to conduct a review of the literature on the usefulness of preimplantation genetic diagnosis in women with Turner syndrome. METHODS: A case of a 27 year-old woman diagnosed with mosaic Turner syndrome and secondary altered ovarian reserve, seen in a referral center for infertility management in Medellín, Colombia. The patient underwent in vitro fertilization followed by pre-implantation genetic testing to prevent transmission of Turner syndrome to her progeny. A literature search was conducted in the Medline via PubMed, Clinical Key, OVID, Embase, Lilacs, SciELO and Oxford Journals databases using the following terms: "Turner Syndrome," "Mosaic Turner," "Preimplantation Genetic Screening," "Preimplantation Genetic Testing," "Preimplantation Genetic Diagnosis," "Pregnancy," "Successful pregnancy." Inclusion criteria were case series and case reports, cohort studies and review articles published between January 1980 and June 2017 that included women with Turner syndrome achieving pregnancy by means of in vitro fertilization techniques with their own oocytes and who had undergone embryo biopsy for preimplantation genetic diagnosis. The search was limited to articles in Spanish and English. RESULTS: one study met the inclusion criteria. Both in this report and in our case, patients with mosaic Turner syndrome underwent several cycles of intracytoplasmic sperm injection (ICSI) with their own eggs, then performed embryonic biopsy for preimplantation genetic analysis using different techniques. In both cases, euploid embryos were transferred to the uterus with the subsequent birth of healthy girls with normal karyotype. CONCLUSIONS: Patients with mosaic Turner syndrome could benefit from preimplantation biopsy and genetic analysis to prevent transmission of the genetic defect to their progeny.
TITULO: RECIÉN NACIDO SANO DESPUÉS DE DIAGNÓSTICO GENÉTICO PREIMPLANTATORIO EN UNA MADRE CON SÍNDROME DE TURNER MOSAICO. REPORTE DE CASO Y REVISIÓN DE LA LITERATURA. OBJETIVO: reportar el caso de una paciente con síndrome de Turner en mosaico, a quien se le realizó un tratamiento de reproducción asistida con análisis genético preimplantatorio para aneuploidias, logrando el nacimiento de una niña sana con cariotipo normal, y realizar una revisión de la literatura sobre la utilidad del diagnóstico genético preimplantatorio en las mujeres con síndrome de Turner. METODOS: se presenta el caso de una mujer de 27 años, con diagnóstico de síndrome de Turner en mosaico y con alteración secundaria en la reserva ovárica, atendida en centro de referencia para el manejo de infertilidad en Medellín, Colombia, a quien se le realizó un tratamiento de fertilización in vitro con análisis genético preimplantatorio para prevenir la transmisión del síndrome de Turner a su descendencia. Se realizó una búsqueda de la literatura en las bases de datos Medline vía PubMed, Clinical Key, OVID, Embase, Lilacs, SciELO y Oxford Journals, con los siguientes términos: "Turner Syndrome", "Mosaic Turner", "Preimplantation Genetic Screening", "Preimplantation Genetic Testing", "Preimplantation Genetic Diagnosis", "Pregnancy", "Successful pregnancy". Como criterios de inclusión se consideraron artículos tipo series y reportes de casos, cohortes y artículos de revisión desde enero de 1980 hasta junio de 2017, que incluyeran mujeres con síndrome de Turner embarazadas por medio de técnicas de fertilización in vitro, con sus propios óvulos, y que hubiesen sido sometidas a biopsia embrionaria para diagnóstico genético preimplantatorio. La búsqueda se limitó a los idiomas español e inglés. RESULTADOS: un estudio cumplió con los criterios de inclusión. Tanto en este reporte como en nuestro caso, las pacientes con síndrome de Turner en mosaico se sometieron a varios ciclos de inyección intracitoplasmática de espermatozoides (ICSI) con sus propios óvulos, luego se realizó biopsia embrionaria para análisis genético preimplantatorio utilizando diferentes técnicas. En ambos casos se logró la transferencia al útero de embriones euploides con el posterior nacimiento de niñas sanas con cariotipo normal. CONCLUSIONES: Las pacientes con ST mosaico podrían beneficiarse de la biopsia embrionaria y análisis genético preimplantatorio para prevenir la transmisión del defecto genético a su descendencia. Palabras clave: síndrome de Turner; aneuploidía; diagnóstico preimplantación; análisis genético preimplantatorio; reserva ovárica.
Assuntos
Mosaicismo , Complicações na Gravidez/genética , Diagnóstico Pré-Implantação , Injeções de Esperma Intracitoplásmicas , Síndrome de Turner/complicações , Adulto , Feminino , Humanos , Recém-Nascido , Infertilidade Feminina/genética , Gravidez , Síndrome de Turner/genética , Síndrome de Turner/prevenção & controleRESUMO
Epigenetics refers to changes in gene function, not resulting from the primary DNA sequence, influenced by the environment. It provides a link between the molecular regulation of the genome and the environmental signals exposed during the life of individuals (including lifestyle, social behavior, development, and nutrition). Notably, early development (intrauterine or postnatal) is highly influenced by the adverse socioeconomic status that leads to malnutrition or obesity; these conditions induce changes over the fetal epigenetic programming and can be transferred by transgenerational inheritance, inducing alterations of the transcription of genes related to several metabolic and neurological processes. Moreover, obesity during pregnancy, and excessive gestational weight gain are associated with an increased risk of fatal pregnancy complications, and adverse cardio-metabolic, respiratory and cognitive-related outcomes of the future child. However, most of our knowledge in this field comes from experimental animal models, that partially resemble the nutritional effects of humans. In this context, nutritional effects implicated in historical famines represent valuable information about the transgenerational effects of undernutrition and stress. In the present review, we attempt to describe the most outstanding results from the most studied famines about the impact of malnutrition on the epigenome.
Assuntos
Envelhecimento/genética , Epigênese Genética , Estado Nutricional/genética , Obesidade/genética , Envelhecimento/patologia , Envelhecimento/fisiologia , Criança , Feminino , Desenvolvimento Fetal/genética , Humanos , Estado Nutricional/fisiologia , Obesidade/fisiopatologia , Fenótipo , Gravidez , Complicações na Gravidez/genética , Complicações na Gravidez/fisiopatologiaRESUMO
The consumption of fructose during pregnancy can cause hyperglycaemia and may stimulate production of reactive oxygen species; however, there are only a few studies reporting whether fructose consumption during pregnancy causes DNA damage. Therefore, the aim of this study was to evaluate the effects of fructose consumption on genetic and biochemical parameters in Swiss mice treated during pregnancy and lactation. For this, 15 couples of 60-day-old Swiss mice were divided into three groups of five couples: negative control (water) and two fructose groups (fructose dose of 10%/l and 20%/l). During this period, we evaluated food consumption, energy efficiency and body weight. Samples of blood were collected from the females before copulation, after the 15th day of conception and on the 21st day after the lactation period, for the glycaemic and lipid profiles as well as comet assay and micronucleus (MN) test. Comet assay and MN test evaluate DNA damage and clastogenicity, respectively. In the gestation and lactation period, the two fructose doses tested showed DNA damage as observed in the comet assay, which is associated with an increase in dietary intake, body weight, lipid profile and fasting glycaemia in females. Thus, it can be suggested that the high consumption of fructose during these periods is harmful for pregnancy and lactation.
Assuntos
Dano ao DNA/efeitos dos fármacos , Frutose/efeitos adversos , Hiperglicemia/genética , Complicações na Gravidez/genética , Animais , Dano ao DNA/genética , Modelos Animais de Doenças , Feminino , Frutose/farmacologia , Humanos , Hiperglicemia/induzido quimicamente , Hiperglicemia/metabolismo , Hiperglicemia/patologia , Lactação/efeitos dos fármacos , Camundongos , Testes para Micronúcleos , Gravidez , Complicações na Gravidez/induzido quimicamente , Complicações na Gravidez/metabolismo , Complicações na Gravidez/patologia , Espécies Reativas de Oxigênio/metabolismoRESUMO
ATP-binding cassette (ABC) subfamily B member 4 (ABCB4), also known as multidrug resistance protein 3 (MDR3), encoded by ABCB4, is involved in biliary phospholipid secretion, protecting hepatobiliary system from deleterious detergent and lithogenic properties of the bile. ABCB4 mutations altering canalicular ABCB4 protein function and expression may have variable clinical presentation and predispose to several human liver diseases. Well-established phenotypes of ABCB4 deficit are: progressive familial intrahepatic cholestasis type 3, gallbladder disease 1 (syn. low phospholipid associated cholelithiasis syndrome), high ɣ-glutamyl transferase intrahepatic cholestasis of pregnancy, chronic cholangiopathy, and adult biliary fibrosis/cirrhosis. Moreover, ABCB4 aberrations may be involved in some cases of drug induced cholestasis, transient neonatal cholestasis, and parenteral nutrition-associated liver disease. Recently, genome-wide association studies have documented occurrence of malignant tumours, predominantly hepatobiliary malignancies, in patients with ABCB4/MDR3 deficit. The patient's age at the time of the first presentation of cholestatic disease, as well as the severity of liver disorder and response to treatment are related to the ABCB4 allelic status. Mutational analysis of ABCB4 in patients and their families should be considered in all individuals with cholestasis of unknown aetiology, regardless of age and/or time of onset of the first symptoms.
Assuntos
Subfamília B de Transportador de Cassetes de Ligação de ATP/deficiência , Doença Hepática Induzida por Substâncias e Drogas/genética , Colelitíase/genética , Colestase Intra-Hepática/genética , Cirrose Hepática Biliar/genética , Complicações na Gravidez/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Idade de Início , Alelos , Doenças dos Ductos Biliares/genética , Colagogos e Coleréticos/uso terapêutico , Colestase/genética , Doenças da Vesícula Biliar/genética , Humanos , Hepatopatias/etiologia , Hepatopatias/genética , Nutrição Parenteral/efeitos adversos , Ácido Ursodesoxicólico/uso terapêuticoRESUMO
In recent years, the vascular endothelium has gained attention as a key player in the initiation and development of pregnancy disorders. Endothelium acts as an endocrine organ that preserves the homeostatic balance by responding to changes in metabolic status. However, in metabolic disorders, endothelial cells adopt a dysfunctional function, losing their normal responsiveness. During pregnancy, several metabolic changes occur, in which endothelial function decisively participates. Similarly, when pregnancy metabolic disorders occur, endothelial dysfunction plays a key role in pathogenesis. This review outlines the main findings regarding endothelial dysfunction in three main metabolic pathological conditions observed during pregnancy: gestational diabetes, hypertensive disorders, and obesity and hyperlipidemia. Organ, histological and cellular characteristics were thoroughly described. Also, we focused in discussing the underlying molecular mechanisms involved in the cellular signaling pathways that mediate responses in these pathological conditions.