RESUMO
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
Although preeclampsia is a common and serious complication of pregnancy, insight into its pathobiology and diagnosis is lacking. Circulating plasma exosomes, which contain RNA and other molecules and have recently become accessible for diagnostics, may be informative in this regard. We tested the hypothesis that preeclampsia may affect the miRNA cargo within circulating maternal blood exosomes. We collected plasma from 60 pregnant women at term, including 20 women with pregnancy complicated by preeclampsia, and 20 women with fetal growth restriction and 20 with healthy pregnancy, serving as controls. We isolated exosomes from the maternal plasma by continuous density gradient ultracentrifugation. Our main outcome variable was exosomal miRNA cargo, analyzed by quantitative polymerase chain reaction-based TaqMan advanced miRNA assay in a card format and the expression of differentially expressed exosomal miRNA in whole plasma from the same participants. We found that 7 miRNA species were differentially expressed in exosomes from women with preeclampsia and those from controls. In contrast, there was no significant difference in exosomal miRNA expression between women with fetal growth restriction and controls. The results were not affected by fetal sex. Only one of the preeclampsia-related, differentially expressed exosomal miRNAs was significantly different in whole plasma miRNA analysis. We concluded that unlike whole plasma miRNA, exosomes extracted from the plasma of women with preeclampsia exhibit a unique miRNA profile, suggesting that plasma exosomal miRNA could provide insight into the pathophysiology of preeclampsia, and may play a role in disease diagnostics.
Assuntos
Exossomos/química , Retardo do Crescimento Fetal/sangue , MicroRNAs/sangue , Pré-Eclâmpsia/sangue , Adulto , Peso ao Nascer , Estudos de Casos e Controles , Feminino , Regulação da Expressão Gênica , Idade Gestacional , Humanos , Recém-Nascido , Masculino , Tamanho do Órgão , Placenta/patologia , Pré-Eclâmpsia/genética , Pré-Eclâmpsia/fisiopatologia , Gravidez , Reação em Cadeia da Polimerase em Tempo Real , Alinhamento de Sequência , Homologia de Sequência do Ácido NucleicoRESUMO
MicroRNAs (miRNAs) constitute a large family of small noncoding RNAs that are encoded by the genomes of most organisms. They regulate gene expression through posttranscriptional mechanisms to attenuate protein output in various genetic networks. The discovery of miRNAs has transformed our understanding of gene regulation and sparked intense efforts intended to harness their potential as diagnostic markers and therapeutic tools. Over the last decade, a flurry of studies has shed light on placental miRNAs but has also raised many questions regarding the scope of their biologic action. Moreover, the recognition that miRNAs of placental origin are released continually in the maternal circulation throughout pregnancy suggested that circulating miRNAs might serve as biomarkers for placental function during pregnancy. Although this generated much enthusiasm, recently recognized challenges have delayed the application of miRNA-based biomarkers and therapeutics in clinical practice. In this review, we summarize key findings in the field and discuss current knowledge related to miRNAs in the context of placental biology.
Assuntos
MicroRNAs/fisiologia , Doenças Placentárias/genética , Biomarcadores/sangue , Espaço Extracelular/metabolismo , Feminino , Humanos , MicroRNAs/sangue , Doenças Placentárias/sangue , GravidezRESUMO
Advancing biomedical knowledge is crucial to the understanding of disease pathophysiology, diagnosis, treatment, and the maintenance of health. Whereas collaborative pursuits among basic and translational scientists, clinical researchers, and clinicians should advance biomedical progress and its translation to better medicine. The field of obstetrics and gynecology and its subspecialties has not escaped this problem. Obstetrics and gynecology specialists and subspecialists have limited opportunities to interact with translational or basic investigators, and cross-fertilization and collaborations are further challenged by the current healthcare and funding climate. This opinion manuscript focuses on the field of maternal-fetal medicine, serving as an example that illustrates the risks and opportunities that might exist within our obstetrics and gynecology academic community. A Pregnancy Task Force recently sought to identify ways to overcome hurdles related to research training, and ensure a sufficient pool of physician-scientists pursuing pertinent questions in the field. The group discussed strategies to promote a culture of intellectual curiosity and research excellence, securing additional resources for trainees, and attracting current and next generation basic, translational, and clinical scholars to our field. Recommendations encompassed activities within annual academic meetings, training initiatives, and additional funding opportunities. Inferences from these discussions can be made to all obstetrics and gynecology subspecialty areas.