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Leslie Myatt

Calais S Prince, Alina Maloyan, Leslie Myatt
INTRODUCTION: Obesity is a major clinical problem in obstetrics being associated with adverse pregnancy outcomes and fetal programming. Brain derived neurotrophic factor (BDNF), a validated miR-210 target, is necessary for placental development, fetal growth, glucose metabolism, and energy homeostasis. Plasma BDNF levels are reduced in obese individuals; however, placental BDNF has yet to be studied in the context of maternal obesity. In this study, we investigated the effect of maternal obesity and sexual dimorphism on placental BDNF signaling...
January 2017: Placenta
Chao Liu, Chunming Guo, Wangsheng Wang, Ping Zhu, Wenjiao Li, Yabing Mi, Leslie Myatt, Kang Sun
The mechanisms underlying human parturition are still not understood, yet we need this knowledge to combat preterm birth. Fetal membranes express abundant 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1), which converts inert cortisone to active cortisol. We examined whether cortisol regeneration in the amnion might play a role in human parturition through regulation of lysyl oxidase (LOX), a collagen cross-linking enzyme, thereby contributing to the rupture of fetal membranes. By using cultured human primary amnion fibroblasts, we demonstrated that, in addition to the induction of the key enzymes involved in prostaglandin E2 (PGE2) synthesis, cortisol stimulated 11β-HSD1 and inhibited LOX reciprocally...
October 2016: Endocrinology
Robert M Silver, Leslie Myatt, John C Hauth, Kenneth J Leveno, Alan M Peaceman, Susan M Ramin, Philip Samuels, George Saade, Yoram Sorokin, Rebecca G Clifton, Uma M Reddy
Objective The objective of this study was to assess the relationship between first trimester cell-free total and fetal DNA in maternal plasma and the subsequent development of preeclampsia. Study Design Nested case-control study of patients enrolled in the Combined Antioxidant and Preeclampsia Prediction Studies prediction study of 175 women who did and 175 women who did not develop preeclampsia. The predictive values of cell-free total and fetal DNA and the subsequent development of preeclampsia were measured using receiver operating characteristic curves...
January 2017: American Journal of Perinatology
Chao Liu, Ping Zhu, Wangsheng Wang, Wenjiao Li, Qun Shu, Zi-Jiang Chen, Leslie Myatt, Kang Sun
No abstract text is available yet for this article.
June 15, 2016: Molecular and Cellular Endocrinology
Brenna L Hughes, Rebecca G Clifton, John C Hauth, Kenneth J Leveno, Leslie Myatt, Uma M Reddy, Michael W Varner, Ronald J Wapner, Brian M Mercer, Alan M Peaceman, Susan M Ramin, Jorge E Tolosa, George Saade, Yoram Sorokin
Objective The objective of this study was to examine whether there is an association between insulin resistance and subsequent development of puerperal infection by measuring insulin resistance in the mid-trimester using the homeostasis model assessment (HOMA:IR). Methods Secondary analysis of low-risk nulliparas enrolled in a multicenter preeclampsia prevention trial. HOMA:IR was measured on fasting plasma glucose and insulin concentrations among low-risk nulliparas between 22 and 26 weeks' gestation. Median HOMA:IR was compared between women who did and did not develop puerperal infection using Wilcoxon rank sum test...
August 2016: American Journal of Perinatology
Sribalasubashini Muralimanoharan, Alina Maloyan, Leslie Myatt
A predisposing factor for development of the hyperglycaemic state of gestational diabetes mellitus (GDM) is obesity. We previously showed that increasing maternal obesity is associated with significant reductions in placental mitochondrial respiration. MicroRNA (miR)-143 has been previously shown to regulate the metabolic switch from oxidative phosphorylation to aerobic glycolysis in cancer tissues. We hypothesized that mitochondrial respiration is reduced and aerobic glycolysis is up-regulated via changes in miR-143 expression in the placenta of women with GDM...
June 1, 2016: Clinical Science (1979-)
Sribalasubashini Muralimanoharan, Xiaoli Gao, Susan Weintraub, Leslie Myatt, Alina Maloyan
The incidence of maternal obesity and its co-morbidities (diabetes, cardiovascular disease) continues to increase at an alarming rate, with major public health implications. In utero exposure to maternal obesity has been associated with development of cardiovascular and metabolic diseases in the offspring as a result of developmental programming. The placenta regulates maternal-fetal metabolism and shows significant changes in its function with maternal obesity. Autophagy is a cell-survival process, which is responsible for the degradation of damaged organelles and misfolded proteins...
May 3, 2016: Autophagy
John V Ilekis, Ekaterini Tsilou, Susan Fisher, Vikki M Abrahams, Michael J Soares, James C Cross, Stacy Zamudio, Nicholas P Illsley, Leslie Myatt, Christine Colvis, Maged M Costantine, David M Haas, Yoel Sadovsky, Carl Weiner, Erik Rytting, Gene Bidwell
Although much progress is being made in understanding the molecular pathways in the placenta that are involved in the pathophysiology of pregnancy-related disorders, a significant gap exists in the utilization of this information for the development of new drug therapies to improve pregnancy outcome. On March 5-6, 2015, the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health sponsored a 2-day workshop titled Placental Origins of Adverse Pregnancy Outcomes: Potential Molecular Targets to begin to address this gap...
July 2016: American Journal of Obstetrics and Gynecology
Chao Liu, Ping Zhu, Wangsheng Wang, Wenjiao Li, Qun Shu, Zi-Jiang Chen, Leslie Myatt, Kang Sun
The underlying mechanism leading to rupture of the membranes at parturition is not fully understood. Lysyl oxidase (LOX) cross-links collagen fibrils thereby increasing the tensile strength of the membranes. Thus, understanding the regulation of LOX expression may be of crucial importance for elucidation of the process of rupture of the fetal membranes. Prostaglandin E2 (PGE2), mainly produced in the amnion, plays crucial roles during human parturition. However it is not known whether PGE2 regulates LOX expression in the fetal membranes...
March 15, 2016: Molecular and Cellular Endocrinology
Mollie McDonnold, Lisa M Mele, Leslie Myatt, John C Hauth, Kenneth J Leveno, Uma M Reddy, Brian M Mercer
Objective In nonpregnant populations the waist-to-hip ratio (WHR) is a better predictor of obesity-related outcomes than body mass index (BMI). Our objective was to determine, in pregnancy, the relationship between these measures of obesity, and large-for-gestational age (LGA) and cesarean delivery (CD). Methods This is a secondary analysis of data from the Combined Antioxidant and Preeclampsia Prediction Study. Women with a WHR of ≥ 0.85 and 0.80 to 0.84 at 9 to 16 weeks gestation were compared with those with a WHR < 0...
May 2016: American Journal of Perinatology
Leslie Myatt, Alina Maloyan
An increasing number of women of reproductive age are obese which affects the continuum of pregnancy and is associated with an increased incidence of adverse maternal and fetal outcomes, including preeclampsia, preterm birth, stillbirth, congenital anomalies, and macrosomia. Maternal obesity is associated with an increased incidence of metabolic and cardiovascular disease later in life in the mother and in the offspring who are developmentally programed by the obese pregnancy environment. The placenta transduces and mediates the effect of the adverse maternal environment to the fetus...
January 2016: Seminars in Reproductive Medicine
Anne Cathrine Staff, Christopher W G Redman, David Williams, Paul Leeson, Kjartan Moe, Basky Thilaganathan, Per Magnus, Eric A P Steegers, Eleni Z Tsigas, Roberta B Ness, Leslie Myatt, Lucilla Poston, James M Roberts
No abstract text is available yet for this article.
February 2016: Hypertension
Wangsheng Wang, Chunming Guo, Ping Zhu, Jiangwen Lu, Wenjiao Li, Chao Liu, Huiliang Xie, Leslie Myatt, Zi-Jiang Chen, Kang Sun
The induction of cyclooxygenase-2 (COX-2) and subsequent production of prostaglandin E2 (PGE2) by cortisol in the amnion contrast with the effect of cortisol on most other tissues, but this proinflammatory effect of cortisol may be a key event in human parturition (labor). We evaluated the underlying mechanism activated by cortisol in primary human amnion fibroblasts. Exposure of the amnion fibroblasts to cortisol led to the activation of the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) pathway, which induced the phosphorylation of the kinase SRC and STAT3 (signal transducer and activator of transcription 3)...
October 27, 2015: Science Signaling
Leslie Myatt, James M Roberts
The focus on disease mechanisms underlying the hypertension and proteinuria defining preeclampsia has increased knowledge of the pathophysiology yet we lack both therapy and predictors. We propose this is in part due to the fact that diagnostic findings identify a "preeclampsia syndrome" but do not necessarily indicate the most important pathophysiology nor if organs are involved as cause or consequence. The increased risk for later life cardiovascular disease in women who develop preeclampsia suggests the stress test of pregnancy exposes pre-existing subclinical vascular disease...
November 2015: Current Hypertension Reports
Sanmaan K Basraon, Lisa Mele, Leslie Myatt, James M Roberts, John C Hauth, Kenneth J Leveno, Michael W Varner, Ronald J Wapner, John M Thorp, Alan M Peaceman, Susan M Ramin, Anthony Sciscione, Jorge E Tolosa, Yoram Sorokin
OBJECTIVE: To determine the risk of gestational diabetes mellitus (GDM) and insulin resistance (IR) in obesity defined by body mass index (BMI), waist-to-hip ratio (WHR), or both combined. METHODS: Secondary analysis of a randomized multicenter trial of antioxidant supplementation versus placebo in nulliparous low-risk women to prevent pregnancy associated hypertension. Women between 9 and 16 weeks with data for WHR and BMI were analyzed for GDM (n = 2,300)...
January 2016: American Journal of Perinatology
Jessica Cantu, Rebecca G Clifton, James M Roberts, Kenneth J Leveno, Leslie Myatt, Uma M Reddy, Michael W Varner, Ronald J Wapner, John M Thorp, Brian M Mercer, Alan M Peaceman, Susan M Ramin, Philip Samuels, Anthony Sciscione, George Saade, Yoram Sorokin
OBJECTIVE: To estimate the frequency of abnormal laboratory test results in pregnancy-associated hypertension and the relationship with pregnancy outcomes. METHODS: This was a secondary analysis of a multicenter trial of vitamin C and E for prevention of pregnancy-associated hypertension in low-risk nulliparous women. Laboratory abnormalities included: platelets less than 100,000/mm, aspartate aminotransferase 100 units/L or greater, creatinine 1.5 mg/dL or greater, lactate dehydrogenase 600 units/L or greater, total bilirubin 1...
November 2014: Obstetrics and Gynecology
Luis Sobrevia, Leslie Myatt, Gregory Rice
No abstract text is available yet for this article.
2014: BioMed Research International
Rossa W K Chiu, Leslie Myatt, Lucas Otaño
From both presentations, it is clear that understanding the APO associated with placental dysfunction represents one of the greatest challenges in the field of prenatal screening, diagnosis, and therapy. Their clinical impact on the health of the mother and child was well recognized by the debaters, and both have agreed that there is a paucity of knowledge in the etiophysiopathology of placental dysfunction and the associated clinical phenotypes. They also agreed that this marked limitation in our understanding is a significant problem when designing a research protocol, and both stressed the importance of proper study designs...
January 2015: Prenatal Diagnosis
James Mele, Sribalasubashini Muralimanoharan, Alina Maloyan, Leslie Myatt
The placenta plays a key role in regulation of fetal growth and development and in mediating in utero developmental programming. Obesity, which is associated with chronic inflammation and mitochondrial dysfunction in many tissues, exerts a programming effect in pregnancy. We determined the effect of increasing maternal adiposity and of fetal sex on placental ATP generation, mitochondrial biogenesis, expression of electron transport chain subunits, and mitochondrial function in isolated trophoblasts. Placental tissue was collected from women with prepregnancy BMI ranging from 18...
September 1, 2014: American Journal of Physiology. Endocrinology and Metabolism
Leslie Myatt, Sribalasubashini Muralimanoharan, Alina Maloyan
In pregnancy fetal growth and development occur in a sexually dimorphic manner. Male and female fetuses respond differently to the intrauterine environment with males disproportionately suffering from perinatal morbidity and mortality. We have demonstrated placental dysfunction and sexually dimorphic responses in pregnancies complicated by severe preeclampsia. Production of cytokines and apoptosis in the male placenta is heightened relative to that of the female placenta. We also find increased expression and stabilization and a sexual dimorphism in expression of the transcription factor HIF-1α, but a defect in binding to the hypoxia response element with corresponding reduced expression of HIF-1α target genes including VEGF and Glut-1...
2014: Advances in Experimental Medicine and Biology
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