Progesterone from maternal circulation binds to progestin receptors in fetal brain

2016 ◽  
Vol 77 (6) ◽  
pp. 767-774 ◽  
Author(s):  
Christine K. Wagner ◽  
Princy Quadros-Mennella
Keyword(s):  
Fetal Brain ◽  
Maternal Circulation ◽  
Progestin Receptors

scholarly journals Corticosteroid Regulation of P-Glycoprotein in the Developing Blood-Brain Barrier

Endocrinology ◽  
2011 ◽  
Vol 152 (3) ◽  
pp. 1067-1079 ◽  
Author(s):  
Majid Iqbal ◽  
William Gibb ◽  
Stephen G. Matthews
Keyword(s):  
Blood Brain Barrier ◽  
Fetal Brain ◽  
Late Gestation ◽  
Brain Barrier ◽  
Protective Capacity ◽  
Maternal Circulation ◽  
Acetoxymethyl Ester ◽  
P Glycoprotein ◽  
Blood Brain ◽  
Brain Microvessel

The early fetal brain is susceptible to teratogens in the maternal circulation, because brain microvessel expression of drug efflux transporter, P-glycoprotein (P-gp), is very low. However, there is a dramatic up-regulation of brain microvessel P-gp in late gestation. This study investigated the role of cortisol and dexamethasone in this up-regulation of fetal brain microvessel P-gp expression. Primary brain endothelial cell (BEC) cultures derived from gestational d (GD)40, GD50, GD65 (term, ∼68 d) and postnatal d 14 male guinea pigs were treated with varying doses (10−8 to 10−5m) of cortisol, dexamethasone, and aldosterone. After treatment, P-gp function was assessed using calcein-acetoxymethyl ester (P-gp substrate; 1 μm for 1 h) and measuring BEC accumulation of calcein. Corticosteroid treatment of BECs derived from postnatal d 14 resulted in increased P-gp activity. BECs derived from GD65 (near term) responded similarly, but these cells were extremely sensitive to the effects of mineralocorticoid receptor agonists (cortisol and aldosterone). BECs derived from GD50 displayed dose-dependent increases in P-gp function with dexamethasone (P < 0.05) and a trend towards increased function with cortisol. Cells derived from GD40 were unresponsive to all treatments. In conclusion, P-gp function in BECs is more responsive to glucocorticoids (GCs) in late gestation. Therefore, the late gestational surge in fetal plasma GCs, which parallels the increase in brain microvessel P-gp expression, may contribute to this P-gp up-regulation. Further, synthetic GCs (administered to pregnant women at risk of preterm delivery) may increase the protective capacity of the developing fetal blood-brain barrier, depending on the timing of GC exposure.

MCI-186 administered to the maternal circulation inhibits fetal brain injury resulting from total umbilical cord occlusion in the chronically instrumented fetal lamb

2006 ◽  
Vol 19 (10) ◽  
pp. 625-631 ◽  
Author(s):  
Naoki Masaoka ◽  
Yoshiyuki Nakajima ◽  
Masao Watanabe ◽  
Yasuhito Hayakawa ◽  
Masaji Nagaishi ◽  
...  
Keyword(s):  
Brain Injury ◽  
Umbilical Cord ◽  
Fetal Brain ◽  
Maternal Circulation ◽  
Fetal Lamb

scholarly journals Prenatal Dynamics of Kynurenine Pathway Metabolism in Mice: Focus on Kynurenic Acid

2017 ◽  
Vol 39 (6) ◽  
pp. 519-528 ◽  
Author(s):  
Nick Goeden ◽  
Francesca M. Notarangelo ◽  
Ana Pocivavsek ◽  
Sarah Beggiato ◽  
Alexandre Bonnin ◽  
...  
Keyword(s):  
Kynurenic Acid ◽  
Ex Vivo ◽  
Fetal Brain ◽  
Maternal Plasma ◽  
Kynurenine Pathway ◽  
Special Focus ◽  
Maternal Circulation ◽  
Placental Perfusion ◽  
Fetal Plasma

The kynurenine pathway (KP), the major catabolic route of tryptophan in mammals, contains several neuroactive metabolites, including kynurenic acid (KYNA) and 3-hydroxykynurenine (3-HK). KP metabolism, and especially the fate of KYNA, during pregnancy is poorly understood, yet it may play a significant role in the development of psychiatric disorders later in life. The present study was designed to investigate the prenatal features of KP metabolism in vivo, with special focus on KYNA. To this end, pregnant CD-1 mice were treated systemically with kynurenine (100 mg/kg), KYNA (10 mg/kg), or saline on embryonic day 18. As expected, administration of either kynurenine or KYNA increased KYNA levels in the maternal plasma and placenta. Maternal kynurenine treatment also raised kynurenine levels in the fetal plasma and brain, demonstrating the ability of this pivotal KP metabolite to cross the placenta and increase the levels of both KYNA and 3-HK in the fetal brain. In contrast, maternal administration of KYNA caused only a small, nonsignificant elevation in KYNA levels in fetal plasma and brain. Complementary experiments using an ex vivo placental perfusion procedure confirmed the significant transplacental transfer of kynurenine and demonstrated that only a very small fraction of maternal kynurenine is converted to KYNA in the placenta and released into the fetal compartment under physiological conditions. Jointly, these results help to clarify the contributions of the maternal circulation and the placenta to fetal KYNA in the late prenatal period.

scholarly journals Acute Effects of Viral Exposure on P-Glycoprotein Function in the Mouse Fetal Blood-Brain Barrier

2017 ◽  
Vol 41 (3) ◽  
pp. 1044-1050 ◽  
Author(s):  
Enrrico Bloise ◽  
Sophie Petropoulos ◽  
Majid Iqbal ◽  
Alisa Kostaki ◽  
Tania Maria Ortiga-Carvalho ◽  
...  
Keyword(s):  
Viral Infection ◽  
Blood Brain Barrier ◽  
Fetal Brain ◽  
Maternal Plasma ◽  
Environmental Toxins ◽  
Brain Barrier ◽  
Fetal Blood ◽  
Maternal Circulation ◽  
P Glycoprotein ◽  
Blood Brain

Background/Aims: Viral infection during pregnancy is known to affect the fetal brain. The toll-like receptor (TLR)-3 is a pattern recognition receptor activated by viruses known to elicit adverse fetal neurological outcomes. The P-glycoprotein (P-gp) efflux transporter protects the developing fetus by limiting the transfer of substrates across both the placenta and the fetal blood-brain barrier (BBB). As such, inhibition of P-gp at these blood-barrier sites may result in increased exposure of the developing fetus to environmental toxins and xenobiotics present in the maternal circulation. We hypothesized that viral exposure during pregnancy would impair P-gp function in the placenta and in the developing BBB. Here we investigated whether the TLR-3 ligand, polyinosinic:polycytidylic acid (PolyI:C), increased accumulation of one P-gp substrate in the fetus and in the developing fetal brain. Methods: Pregnant C57BL/6 mice (GD15.5) were injected (i.p.) with PolyI:C (5 mg/kg or 10 mg/kg) or vehicle (saline). [3H]digoxin (P-gp substrate) was injected (i.v.) 3 or 23h post-treatment and animals were euthanized 1h later. Maternal plasma, ‘fetal-units’ (fetal membranes, amniotic fluid and whole fetus), and fetal brains were collected. Results: PolyI:C exposure (4h) significantly elevated maternal plasma IL-6 (P<0.001) and increased [3H]digoxin accumulation in the fetal brain (P<0.05). In contrast, 24h after PolyI:C exposure, no effect on IL-6 or fetal brain accumulation of P-gp substrate was observed. Conclusion: Viral infection modeled by PolyI:C causes acute increases in fetal brain accumulation of P-gp substrates and by doing so, may increase fetal brain exposure to xenobiotics and environmental toxins present in the maternal circulation.

scholarly journals A Mathematical Model Relating Pitocin Use during Labor with Offspring Autism Development in terms of Oxytocin Receptor Desensitization in the Fetal Brain

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Mark M. Gottlieb
Keyword(s):  
Mathematical Model ◽  
Infusion Rate ◽  
Medical Information ◽  
Fetal Brain ◽  
Subsequent Development ◽  
Epidemiological Studies ◽  
Maternal Weight ◽  
Yale University ◽  
Maternal Circulation ◽  
Duke University

This paper develops a mathematical model describing the potential buildup of high oxytocin concentrations in the maternal circulation during labor in terms of continuous Pitocin infusion rate, half-life, and maternal weight. Oxytocin override of the degradation of oxytocin by placental oxytocinase is introduced to model the potential transfer of oxytocin from the maternal circulation across the placenta into the fetal circulation and from there into the brain of the fetus. The desensitization unit D equal to 1.8E6 (pg·min)/ml is employed to establish a desensitization threshold and by extension, a downregulation threshold as a function of oxytocin override concentration and continuous Pitocin infusion time, that could be a factor in the subsequent development of autism among offspring. Epidemiological studies by Duke University [1], Yale University [2], and Harvard University [3] are discussed regarding Pitocin use and offspring autism development for an explanation of the weak correlations they identified. The findings of the Harvard epidemiological study are reinterpreted regarding Pitocin use and its conclusion questioned. Further evaluations of the findings of these three epidemiological studies are called for to incorporate medical information on quantity of Pitocin used, continuous Pitocin infusion rate, length of labor, and maternal weight to determine if a correlation can be established with offspring autism development above an empirically determined desensitization threshold for Pitocin use. Suggestions for research are discussed, including an alternative to continuous Pitocin infusion, pulsatile infusion of Pitocin during labor induction, which may mitigate possible offspring autism development.

scholarly journals Maternal Obesity and IL-6 Lead to Aberrant Developmental Gene Expression and Deregulated Neurite Growth in the Fetal Arcuate Nucleus

Endocrinology ◽  
2014 ◽  
Vol 155 (7) ◽  
pp. 2566-2577 ◽  
Author(s):  
Tessa R. Sanders ◽  
Dong Won Kim ◽  
Kelly A. Glendining ◽  
Christine L. Jasoni
Keyword(s):  
Gene Expression ◽  
Arcuate Nucleus ◽  
Maternal Obesity ◽  
Fetal Brain ◽  
Neurite Growth ◽  
Normal Weight ◽  
Causative Role ◽  
Developmental Gene ◽  
Maternal Circulation ◽  
Developmental Gene Expression

Maternal obesity during pregnancy increases the risk of obesity in the offspring. Several observations have pointed to a causative role for the proinflammatory cytokine IL-6, but whether it is present in the fetal circulation and how it acts on the developing fetus are unclear. We first observed that postnatal day 0 offspring from obese mothers had significantly reduced neuropeptide Y (NPY) innervation of the paraventricular nucleus (PVN) compared with that for offspring of normal-weight controls. Thus, the growth of NPY neurites from the arcuate nucleus (ARC) was impaired in the fetal brain by maternal obesity. The neurite growth regulator, Netrin-1, was expressed in the ARC and PVN and along the pathway between the two at gestational day (GD) 17.5 in normal animals, making it likely to be involved in the development of NPY ARC-PVN projections. In addition, the expression of Dcc and Unc5d, receptors for Netrin-1, were altered in the GD17.5 ARC in obese but not normal weight pregnancies. Thus, this important developmental pathway is perturbed by maternal obesity and may explain the defect in NPY innervation of the PVN that occurs in fetuses developing in obese mothers. To investigate whether IL-6 may play a role in these developmental changes, we found first that IL-6 was significantly elevated in the fetal and maternal circulation in pregnancies of obese mice compared with those of normal-weight mice. In addition, treatment of GD17.5 ARC tissue with IL-6 in vitro significantly reduced ARC neurite outgrowth and altered developmental gene expression similar to maternal obesity in vivo. These findings demonstrate that maternal obesity may alter the way in which fetal ARC NPY neurons respond to key developmental signals that regulate normal prenatal neural connectivity and suggest a causative role for elevated IL-6 in these changes.

The role of placental growth factor in regulating fetal brain vascular development

2014 ◽  
Author(s):  
Matthew T Ratsep ◽  
Bruno Zavan ◽  
Nicki Peterson ◽  
Leandra Tolusso ◽  
Vanessa Kay ◽  
...  
Keyword(s):  
Growth Factor ◽  
Vascular Development ◽  
Fetal Brain ◽  
Placental Growth Factor

Fetal Brain Activity in Pregnancy of Women with Type 1 Diabetes Mellitus

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1402-P
Author(s):  
ELLEN FEHLERT ◽  
FRANZISKA SCHLEGER ◽  
KATARZYNA LINDER ◽  
MARTIN HENI ◽  
HANS-ULRICH HAERING ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Brain Activity ◽  
Fetal Brain ◽  
In Pregnancy

CEREBRAL PALSY:A CLINICAL OVERVIEW

2020 ◽  
Vol 3 (1) ◽  
pp. 54-59
Author(s):  
Nargiza Ergasheva ◽  
◽  
Sardor Anorboev ◽  
Gavkhar Kendjaeva ◽  
Keyword(s):  
Brain Area ◽  
Fetal Brain ◽  
Clinical History ◽  
Screening Tests ◽  
Spastic Diplegia ◽  
Team Approach ◽  
Birth Process ◽  
Increased Risk ◽  
Spastic Quadriplegia ◽  
Magnetic Resonance Imaging Mri

Cerebral palsy (CP) is a disorder characterized by abnormal tone, posture and movement. The incidence of CP is 2–4 per 1,000 live births in the world. Prematurityand low birth weight are important risk factors for CP; however, multiple other factors have been associated with an increased risk for CP, including maternal infections and diseases, and abnormal birth process. In most cases of CP the initial injury to the brain occurs during early fetal brain development, later a brain area that is injured cannot function properly in the future. CP is classified clinically based on the predominant motor syndrome—spastic hemiplegia, spastic diplegia, spastic quadriplegia, ataxic and dyskinetic cerebral palsies. The diagnosis of CPis based on a combination of clinical history, use of standardized neuromotor assessment and findings on magnetic resonance imaging (MRI). If there is a suspicionof genetic or inborn metabolic disorders, screening tests should be provided additionally. Because CP is associated with multiple associated and secondary medical conditions, its management requires a multidisciplinary team approach

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