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hpa and fetus

Assaf Arie Barg, Aviya Dvir Ifrah, Tzipi Strauss, Michal J Simchen, Raoul Orvieto, Nurit Rosenberg, Gili Kenet
The incompatibility causing fetal and neonatal alloimmune thrombocytopenia (FNAIT) results from a fetus inheriting a paternal human platelet antigen (HPA), which is different from the maternal HPA. We present a unique case of FNAIT in a pregnancy involving an oocyte recipient mother with Turner syndrome. This is the first report of FNAIT in which the suggested mechanism involves antibodies produced by a gestational mother against the incompatible HPA of the oocyte donor.
January 18, 2017: Pediatric Blood & Cancer
Gemma L Crighton, Ri Scarborough, Zoe K McQuilten, Louise E Phillips, Helen F Savoia, Bronwyn Williams, Rhonda Holdsworth, Amanda Henry, Erica M Wood, Stephen A Cole
OBJECTIVE: To describe the natural history, antenatal and postnatal therapy, and clinical outcomes of Australian patients with fetomaternal/neonatal alloimmune thrombocytopenia (NAIT) recorded in the Australian NAIT Registry. METHODS: Analysis of registry data of Australian mothers treated antenatally for NAIT and any fetus/newborn with thrombocytopenia (TCP) and maternal human platelet antigen (HPA) antibodies. RESULTS: 94 potential cases (91 pregnancies; three twin pregnancies) were registered between December 2004 and September 2015 with 76 confirmed or treated as NAIT...
November 2, 2016: Journal of Maternal-fetal & Neonatal Medicine
Elysia Poggi Davis, Kevin Head, Claudia Buss, Curt A Sandman
Glucocorticoids (cortisol in humans) are the end product of the hypothalamic-pituitary-adrenocortical (HPA) axis and are proposed as a key mechanism for programming fetal brain development. The present prospective longitudinal study evaluates the association between prenatal maternal cortisol concentrations and child neurodevelopment. Participants included a low risk sample of 91 mother-child pairs. Prenatal maternal plasma cortisol concentrations were measured at 19 and 31 gestational weeks. Brain development and cognitive functioning were assessed when children were 6-9 years of age...
January 2017: Psychoneuroendocrinology
Marije M Kamphuis, Heidi Tiller, E S van den Akker, Magnus Westgren, Eleonor Tiblad, Dick Oepkes
OBJECTIVE: To evaluate the management and outcome of a large international cohort of cases of pregnancies complicated by fetal and neonatal alloimmune thrombocytopenia (FNAIT). METHODS: This was an observational prospective and retrospective cohort study of all cases of FNAIT entered into the international multicentre No IntraCranial Haemorrhage (NOICH) registry during the period of 2001-2010. We evaluated human platelet antigen (HPA) specificity, the antenatal and postnatal interventions performed, and clinical outcome...
October 12, 2016: Fetal Diagnosis and Therapy
María Emilia Solano, Megan C Holmes, Paul R Mittelstadt, Karen E Chapman, Eva Tolosa
Endogenous levels of glucocorticoids rise during pregnancy to warrant development and maturation of the fetal organs close to birth. However, during most of the gestation, the fetus is protected from excessive biologically active endogenous glucocorticoids by placental and fetal expression of 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2). Maternal stress, which may overwhelm placental 11β-HSD2 activity with high glucocorticoid levels, or administration of synthetic glucocorticoids to improve the survival chances of the premature newborn, are associated to postnatal increased risk for immune diseases...
November 2016: Seminars in Immunopathology
Milica Manojlović-Stojanoski, Nataša Nestorović, Svetlana Trifunović, Nataša Ristić, Ivana Jarić, Branko Filipović, Verica Milošević
The hypothalamic paraventricular nucleus (PVN) drives the stress response by activating the hypothalamo-pituitary-adrenal (HPA) axis, particularly vulnerable to glucocorticoid exposure during development. To evaluate the effects of fetal dexamethasone (Dx) exposure on the stereological features of PVN and HPA axis activity in female rat fetuses, pregnant rats received 0.5mg Dx/kg/b.w./day on days 16, 17 and 18 of pregnancy and 21-day-old fetuses were obtained; controls received the same volume of saline. In an unbiased stereological approach, Cavalieri's principle and an optical fractionator were used for estimating volume and total cell number of the PVN, respectively...
October 2016: Tissue & Cell
M N Edelmann, C A Sandman, L M Glynn, D A Wing, E P Davis
Due to the rapid developmental changes that occur during the fetal period, prenatal influences can affect the developing central nervous system with lifelong consequences for physical and mental health. Glucocorticoids are one of the proposed mechanisms by which fetal programing occurs. Glucocorticoids pass through the blood-brain barrier and target receptors throughout the central nervous system. Unlike endogenous glucocorticoids, synthetic glucocorticoids readily pass through the placental barrier to reach the developing fetus...
October 2016: Psychoneuroendocrinology
Michelle Dreiling, Sabine Bischoff, Rene Schiffner, Sven Rupprecht, Michael Kiehntopf, Harald Schubert, Otto W Witte, Peter W Nathanielsz, Matthias Schwab, Florian Rakers
Prenatal maternal stress can be transferred to the fetus via a catecholamine-dependent decrease of uterine blood flow (UBF). However, it is unclear which group of adrenergic receptors mediates this mechanism of maternal-fetal stress transfer. We hypothesized that in sheep, alpha 1-adrenergic receptors may play a key role in catecholamine mediated UBF decrease, as these receptors are mainly involved in peripheral vasoconstriction and are present in significant number in the uterine vasculature. After chronic instrumentation at 125 ± 1 days of gestation (dGA; term 150 dGA), nine pregnant sheep were exposed at 130 ± 1 dGA to acute isolation stress for one hour without visual, tactile, or auditory contact with their flockmates...
September 2016: Stress: the International Journal on the Biology of Stress
Ali-Akbar Salari, Laleh Fatehi-Gharehlar, Negar Motayagheni, Judith R Homberg
Maternal depression during pregnancy and the postpartum period (lactation) is a common debilitating condition affecting mother-fetus/-infant interactions, which can be a risk factor for cognitive and affective disorders in mothers and their children. Selective-serotonin-reuptake-inhibitor-(SSRI) pharmacotherapy is known as the first-line treatment of maternal depression. However, its use during pregnancy and lactation is a topic of concern. The present study aimed to investigate the effects of prenatal stress alone or in combination with fluoxetine (FLX) on hypothalamic-pituitary-adrenal axis (HPA) activity, anxiety-/depression-like behaviors in dams and in offspring...
September 15, 2016: Behavioural Brain Research
Eleana Gkioka, Laskarina Maria Korou, Afrodite Daskalopoulou, Angelica Misitzi, Eleni Batsidis, Ioannis Bakoyiannis, Vasilios Pergialiotis
It is estimated that approximately 0.5%-3% of fetuses are prenatally exposed to cocaine (COC). The neurodevelopmental implications of this exposure are numerous and include motor skill impairments, alterations of social function, predisposition to anxiety, and memory function and attention deficits; these implications are commonly observed in experimental studies and ultimately affect both learning and IQ. According to previous studies, the clinical manifestations of prenatal COC exposure seem to persist at least until adolescence...
July 1, 2016: Reviews in the Neurosciences
Charles E Wood, Maureen Keller-Wood
The fetal hypothalamus-pituitary-adrenal (HPA) axis is at the center of mechanisms controlling fetal readiness for birth, survival after birth and, in several species, determination of the timing of birth. Stereotypical increases in fetal HPA axis activity at the end of gestation are critical for preparing the fetus for successful transition to postnatal life. The fundamental importance in fetal development of the endogenous activation of this endocrine axis at the end of gestation has led to the use of glucocorticoids for reducing neonatal morbidity in premature infants...
2016: F1000Research
Darlene A Kertes, Hayley S Kamin, David A Hughes, Nicole C Rodney, Samarth Bhatt, Connie J Mulligan
Exposure to stress early in life permanently shapes activity of the hypothalamic-pituitary-adrenocortical (HPA) axis and the brain. Prenatally, glucocorticoids pass through the placenta to the fetus with postnatal impacts on brain development, birth weight (BW), and HPA axis functioning. Little is known about the biological mechanisms by which prenatal stress affects postnatal functioning. This study addresses this gap by examining the effect of chronic stress and traumatic war-related stress on epigenetic changes in four key genes regulating the HPA axis in neonatal cord blood, placenta, and maternal blood: CRH, CRHBP, NR3C1, and FKBP5...
January 2016: Child Development
Dean A Myers, Krista Singleton, Christy Kenkel, Kanchan M Kaushal, Charles A Ducsay
Maturation of the fetal hypothalamo-pituitary-adrenocortical (HPA) axis is critical for organ maturation necessary for the fetus to transition to the ex-utero environment. Intrauterine stressors can hasten maturation of the HPA axis leading to fetal growth restriction and in sheep, premature birth. We have previously reported that high-altitude mediated, long-term-moderate gestational hypoxia (LTH) during gestation has a significant impact on the fetal HPA axis. Significant effects were observed at the level of both the anterior pituitary and adrenal cortex resulting in elevated plasma ACTH during late gestation with decreased adrenocortical expression of enzymes rate limiting for cortisol synthesis...
January 2016: Physiological Reports
Andrea Constantinof, Vasilis G Moisiadis, Stephen G Matthews
The embryo and fetus are highly responsive to the gestational environment. Glucocorticoids (GC) represent an important class of developmental cues and are crucial for normal brain development. Levels of GC in the fetal circulation are tightly regulated. They are maintained at low levels during pregnancy, and increase rapidly at the end of gestation. This surge in GC is critical for maturation of the organs, specifically the lungs, brain and kidney. There are extensive changes in brain epigenetic profiles that accompany the GC surge, suggesting that GC may drive regulation of gene transcription through altered epigenetic pathways...
June 2016: Journal of Steroid Biochemistry and Molecular Biology
Hevi Wihadmadyatami, Kathrin Heidinger, Lida Röder, Silke Werth, Astrid Giptner, Holger Hackstein, Martin Knorr, Gregor Bein, Ulrich J Sachs, Sentot Santoso
BACKGROUND: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is caused by the destruction of platelets (PLTs) in the fetus or newborn by maternal PLT antibodies that crossed the placenta during pregnancy. STUDY DESIGN AND METHODS: In this study, we aim to elucidate the properties of a new PLT alloantigen (Lap(a)) that is associated with a severe case of FNAIT. Analysis of maternal serum with phenotyped PLTs by monoclonal antibody-specific immobilization of platelet antigens showed positive reaction against PLT glycoprotein (GP)IIb/IIIa and HLA Class I expressed on paternal PLTs...
December 2015: Transfusion
Bridget M Nugent, Tracy L Bale
Fetal development could be considered a sensitive period wherein exogenous insults and changes to the maternal milieu can have long-term impacts on developmental programming. The placenta provides the fetus with protection and necessary nutrients for growth, and responds to maternal cues and changes in nutrient signaling through multiple epigenetic mechanisms. The X-linked enzyme O-linked-N-acetylglucosamine transferase (OGT) acts as a nutrient sensor that modifies numerous proteins to alter various cellular signals, including major epigenetic processes...
October 2015: Frontiers in Neuroendocrinology
N Lan, M P Y Chiu, L Ellis, J Weinberg
Adverse intrauterine environments increase vulnerability to chronic diseases across the lifespan. The hypothalamic-pituitary-adrenal (HPA) axis, which integrates multiple neuronal signals and ultimately controls the response to stressors, may provide a final common pathway linking early adversity and adult diseases. Both prenatal alcohol exposure (PAE) and prenatal stress (PS) induce a hyperresponsive HPA phenotype in adulthood. As glucocorticoids are pivotal for the normal development of many fetal tissues including the brain, we used animal models of PAE and PS to investigate possible mechanisms underlying fetal programing of glucocorticoid signaling in the placenta and fetal brain at gestation day (GD) 21...
February 7, 2017: Neuroscience
Ying Fai Ngai, Dian C Sulistyoningrum, Ryan O'Neill, Sheila M Innis, Joanne Weinberg, Angela M Devlin
Prenatal alcohol exposure (PAE) programs the fetal hypothalamic-pituitary-adrenal (HPA) axis, resulting in HPA dysregulation and hyperresponsiveness to stressors in adulthood. Molecular mechanisms mediating these alterations are not fully understood. Disturbances in one-carbon metabolism, a source of methyl donors for epigenetic processes, contributes to alcoholic liver disease. We assessed whether PAE affects one-carbon metabolism (including Mtr, Mat2a, Mthfr, and Cbs mRNA) and programming of HPA function genes (Nr3c1, Nr3c2, and Slc6a4) in offspring from ethanol-fed (E), pair-fed (PF), and ad libitum-fed control (C) dams...
September 2015: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Elizabeth A Newby, Dean A Myers, Charles A Ducsay
In utero, hypoxia is a significant yet common stress that perturbs homeostasis and can occur due to preeclampsia, preterm labor, maternal smoking, heart or lung disease, obesity, and high altitude. The fetus has the extraordinary capacity to respond to stress during development. This is mediated in part by the hypothalamic-pituitary-adrenal (HPA) axis and more recently explored changes in perirenal adipose tissue (PAT) in response to hypoxia. Obvious ethical considerations limit studies of the human fetus, and fetal studies in the rodent model are limited due to size considerations and major differences in developmental landmarks...
September 1, 2015: American Journal of Physiology. Endocrinology and Metabolism
Suzanne King, Sue Kildea, Marie-Paule Austin, Alain Brunet, Vanessa E Cobham, Paul A Dawson, Mark Harris, Elizabeth M Hurrion, David P Laplante, Brett M McDermott, H David McIntyre, Michael W O'Hara, Norbert Schmitz, Helen Stapleton, Sally K Tracy, Cathy Vaillancourt, Kelsey N Dancause, Sue Kruske, Nicole Reilly, Laura Shoo, Gabrielle Simcock, Anne-Marie Turcotte-Tremblay, Erin Yong Ping
BACKGROUND: Retrospective studies suggest that maternal exposure to a severe stressor during pregnancy increases the fetus' risk for a variety of disorders in adulthood. Animal studies testing the fetal programming hypothesis find that maternal glucocorticoids pass through the placenta and alter fetal brain development, particularly the hypothalamic-pituitary-adrenal axis. However, there are no prospective studies of pregnant women exposed to a sudden-onset independent stressor that elucidate the biopsychosocial mechanisms responsible for the wide variety of consequences of prenatal stress seen in human offspring...
2015: BMC Pregnancy and Childbirth
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