107 research outputs found
Placental Related Disorders of Pregnancy
No full textThe Special Issue “Placental Related Disorders of Pregnancy” was edited by Dr Hiten D. Mistry, Department of Women and Children's Health, School of Life Course and Population Health Sciences, King's College London, London, UK and Dr Eun D. Lee, Department of Obstetrics and Gynecology, Virginia Commonwealth University Health System, Richmond, VA, USA
Androgens Tend to Be Higher, but What about Altered Progesterone Metabolites in Boys and Girls with Autism?
Full text linkBackground: Evidence exists that steroid hormones are altered in individuals with autism, especially androgens. Despite lower prevalence in girls than boys, evidence of potential alterations in progesterone metabolites is sparse, so the aim of this study was to elucidate different progesterone metabolites in affected children with autism versus healthy controls. Material and Methods: Circadian urine samples from 48 boys and 16 girls with autism spectrum disorders and a matched case–control group were analysed for progesterone metabolites by gas chromatography–mass spectrometry and normalised for creatinine excretion. Results: In boys with autism, the majority of progesterone metabolites were reduced, such as progesterone, 6a-OH-3a5b-TH-progesterone, or 20a-DH-progesterone (p < 0.01 for all). In girls with autism, a similar pattern of reduction in progesterone metabolites was detected; however, potentially due to the relatively small sample, this pattern was only detectable on the level of a trend. Discussion: As stated, androgen levels are higher in boys and girls with autism, but evidence for progesterone metabolites is much sparser. The pattern of a decrease in progesterone metabolites suggests the existence of an altered routing of steroid metabolites, probably in combination with a dysregulation of the HPAG axis. As, recently, increased CYP17A1 activity has been suggested, the stronger routing towards androgens is further implied in line with our findings of lower progesterone concentrations in boys and girls with autism than healthy controls
Blood pressure measurement and adverse pregnancy outcomes: a cohort study testing blood pressure variability and alternatives to 140/90 mmHg
No full textObjective: To examine the association with adverse pregnancy outcomes of: (1) American College of Cardiology/American Heart Association blood pressure (BP) thresholds, and (2) visit-to-visit BP variability (BPV), adjusted for BP level. Design: An observational study. Setting: Analysis of data from the population-based UK Southampton Women's Survey (SWS). Population or sample: 3003 SWS participants. Methods: Generalised estimating equations were used to estimate crude and adjusted relative risks (RRs) of adverse pregnancy outcomes by BP thresholds, and by BPV (as standard deviation [SD], average real variability [ARV] and variability independent of the mean [VIM]). Likelihood ratios (LRs) were calculated to evaluate diagnostic test properties, for BP at or above a threshold, compared with those below. Main outcome measures: Gestational hypertension, severe hypertension, pre-eclampsia, preterm birth (PTB), small-for-gestational-age (SGA) infants, neonatal intensive care unit (NICU) admission. Results: A median of 11 BP measurements were included per participant. For BP at ≥20 weeks’ gestation, higher BP was associated with more adverse pregnancy outcomes; however, only BP <140/90 mmHg was a good rule-out test (negative LR <0.20) for pre-eclampsia and BP ≥140/90 mmHg a good rule-in test (positive LR >8.00) for the condition. BP ≥160/110 mmHg could rule-in PTB, SGA infants and NICU admission (positive LR >5.0). Higher BPV (by SD, ARV, or VIM) was associated with gestational hypertension, severe hypertension, pre-eclampsia, PTB, SGA and NICU admission (adjusted RRs 1.05–1.39). Conclusions: While our findings do not support lowering the BP threshold for pregnancy hypertension, they suggest BPV could be useful to identify elevated risk of adverse outcomes.</p
Blood pressure measurement and adverse pregnancy outcomes - a cohort study testing blood pressure variability and alternatives to 140/90mmHg
No full textObjective: to examine the relationship with adverse pregnancy outcomes of: (1) American College of Cardiology/American Heart Association blood pressure (BP) thresholds, and (2) visit-to-visit BP variability (BPV), adjusted for BP level.Design: an observational study.Setting: analysis of data from the population-based UK Southampton Women’s Survey (SWS).Population or Sample: 3003 SWS participants.Methods: generalised estimating equations were used to estimate crude and adjusted relative risks (RRs) of adverse pregnancy outcomes by BP thresholds, and by BPV (as standard deviation [SD], average real variability [ARV], and variability independent of the mean [VIM]). Likelihood ratios (LRs) were calculated to evaluate diagnostic test properties, for BP at or above a threshold, compared with those below.Main Outcome Measures: gestational hypertension, severe hypertension, pre-eclampsia, preterm birth (PTB), small-for-gestational-age (SGA) infants, neonatal intensive care unit (NICU) admission.Results: a median of 11 BP measurements were included per participant. For BP at ≥20 weeks’ gestation, higher BP was associated with more adverse pregnancy outcomes; however, only BP <140/90mmHg was a good rule-out test (negative LR <0.20) for pre-eclampsia, and BP ≥140/90mmHg a good rule-in test (positive LR >8.00) for the condition. BP ≥160/110mmHg could rule-in PTB, SGA infants, and NICU admission (positive LR >5.0). Higher BPV (by SD, ARV, or VIM) was associated with gestational hypertension, severe hypertension, pre-eclampsia, PTB, SGA, and NICU admission (adjusted RRs 1.05-1.39).Conclusions: while our findings do not support lowering the BP threshold for pregnancy hypertension, they suggest BPV could be useful to identify elevated risk of adverse outcomes.<br/
Do lower antenatal blood pressure cut-offs in pregnant women with obesity identify those at greater risk of adverse maternal and perinatal outcomes? A secondary analysis of data from the UK Pregnancies Better Eating and Activity Trial (UPBEAT)
No full textBackground: obesity is a major risk-factor for adverse pregnancy outcomes. While the 2017 American College of Cardiology/American Heart Association (ACC/AHA) classification of normal and abnormal blood pressure (BP) outside pregnancy has been suggested for use in pregnancy, the impact on adverse outcomes has not been examined specifically in women with obesity.Methods: the UK Pregnancies Better Eating and Activity Trial (UPBEAT) enroled women with a body mass index (BMI) ≥ 30 kg/m2. In secondary analyses, maximal antenatal BP was categorised by 2017 ACC/AHA criteria: ‘Normal’ BP (systolic [sBP] <120 mmHg and diastolic [dBP] <80 mmHg), ‘Elevated’ BP (sBP 120–129 mmHg and dBP <80 mmHg), ‘Stage 1 hypertension’ (sBP 130–139 mmHg and/or dBP 80-89 mmHg), and ‘Stage 2 hypertension’ (sBP ≥140 mmHg and/or dBP ≥90 mmHg, non-severe [sBP 140-159 mmHg and/or dBP 90–109 mmHg] and severe (sBP ≥160 mmHg and/or dBP ≥110 mmHg). Main outcomes were preterm birth, postpartum haemorrhage (PPH), birthweight <10th centile (small-for-gestational age, SGA), and neonatal intensive care unit (NICU) admission. Associations with adverse outcomes were adjusted for UPBEAT intervention, maternal age, booking BMI, ethnicity, parity, smoking, alcohol, and previous pre-eclampsia or gestational diabetes. Diagnostic test properties (positive and negative likelihood ratios, -LR and +LR) were assessed as individual categories (vs. ‘Normal’ BP), and as threshold values.Results: severe ‘Stage 2 hypertension’ (vs. BP < 160/110 mmHg) was associated with PPH (RR 2.57 (1.35, 4.86)) and SGA (RR 2.52 (1.05, 6.07)) only in unadjusted analyses. No outcomes were associated with ‘Stage 1 hypertension’ or ‘Elevated BP’. All +LR were <5.0 and -LR ≥ 0.20, indicating that no BP threshold was useful as a diagnostic test to detect preterm birth, PPH, SGA, or NICU admission.Conclusions: among pregnant women with obesity, we found no evidence that lowering the antenatal BP considered to be abnormal (from 140/90 mmHg) would assist in identifying women and babies at risk
Evidence for hypoxia-induced dysregulated cholesterol homeostasis in preeclampsia: Insights into the mechanisms from human placental cells and tissues.
Full text linkPreeclampsia (PE) poses a considerable risk to the long-term cardiovascular health of both mothers and their offspring due to a hypoxic environment in the placenta leading to reduced fetal oxygen supply. Cholesterol is vital for fetal development by influencing placental function. Recent findings suggest an association between hypoxia, disturbed cholesterol homeostasis, and PE. This study investigates the influence of hypoxia on placental cholesterol homeostasis. Using primary human trophoblast cells and placentae from women with PE, various aspects of cholesterol homeostasis were examined under hypoxic and hypoxia/reoxygenation (H/R) conditions. Under hypoxia and H/R, intracellular total and non-esterified cholesterol levels were significantly increased. This coincided with an upregulation of HMG-CoA-reductase and HMG-CoA-synthase (key genes regulating cholesterol biosynthesis), and a decrease in acetyl-CoA-acetyltransferase-1 (ACAT1), which mediates cholesterol esterification. Hypoxia and H/R also increased the intracellular levels of reactive oxygen species and elevated the expression of hypoxia-inducible factor (HIF)-2α and sterol-regulatory-element-binding-protein (SREBP) transcription factors. Additionally, exposure of trophoblasts to hypoxia and H/R resulted in enhanced cholesterol efflux to maternal and fetal serum. This was accompanied by an increased expression of proteins involved in cholesterol transport such as the scavenger receptor class B type I (SR-BI) and the ATP-binding cassette transporter G1 (ABCG1). Despite these metabolic alterations, mitogen-activated-protein-kinase (MAPK) signaling, a key regulator of cholesterol homeostasis, was largely unaffected. Our findings indicate dysregulation of cholesterol homeostasis at multiple metabolic points in both the trophoblast hypoxia model and placentae from women with PE. The increased cholesterol efflux and intracellular accumulation of non-esterified cholesterol may have critical implications for both the mother and the fetus during pregnancy, potentially contributing to an elevated cardiovascular risk later in life
COMPARISON OF IN VITRO PRE-ECLAMPSIA (PE) CELL MODELS WITH PE PLACENTAL TISSUE
No full textObjectives: We induced hypoxia and oxidative stress (OS) in cytotrophoblasts
(CTB) from control placentae to mimic the characteristics of preeclampsia
(PE). For validation we compared the gene and protein
expression of established PE biomarkers between the cell models and PE
placentae.
Methods: CTB isolated from healthy term placentae (n¼2) were cultured
either under normoxic (5% pCO2;21% pO2;24h), hypoxic (5% pCO2;1.5%
pO2;24h) or OS (consecutive 6h-intervals of normoxia and hypoxia until
24h) conditions. mRNA abundances of PE biomarkers (Table1) were analysed
by qRT-PCR in the cell models and PE placentae (n¼12). Additionally,
the secretion of sFlt1 and PlGF was determined by ELISA in cell culture
supernatants. Statistical analysis was performed using unpaired t-test.
Results: The cell models recapitulated important pathophysiological
changes occurring in PE (Table1) including the upregulation of sFlt1 which
was also observed in PE placentae. Interestingly, in the cell models the
sFlt1/PlGF ratio was above the clinically applied cutoff value of 38 for
hypoxic (77.3±35.2) and OS (124±88.3), but <38 for normoxic (19.4±16)
conditions.
nm-not measured
Conclusion: The established cell models are mimicking important characteristics
of PE. The sFlt1/PlGF ratio obtained in cell models is in agreement
with reports proposing sFlt1/PlGF as predictive diagnostic marker for
PE. Thus, hypoxia and OS induced in primary CTB can serve as suitable
models to study the detailed mechanisms of PE
Primary Human Trophoblasts Mimic the Preeclampsia Phenotype after Acute Hypoxia-Reoxygenation Insult.
Full text linkPreeclampsia (PE) is a pregnancy-specific disorder that affects 3 to 5% of pregnancies worldwide and is one of the leading causes of maternal and fetal morbidity and mortality. Nevertheless, how these events occur remains unclear. We hypothesized that the induction of hypoxic conditions in vitro in primary human trophoblast cells would mimic several characteristics of PE found in vivo. We applied and characterized a model of primary cytotrophoblasts isolated from healthy pregnancies that were placed under different oxygen concentrations: ambient O2 (5% pCO2, 21%pO2, 24 h, termed "normoxia"), low O2 concentration (5% pCO2, 1.5% pO2, 24 h, termed "hypoxia"), or "hypoxia/reoxygenation" (H/R: 6 h intervals of normoxia and hypoxia for 24 h). Various established preeclamptic markers were assessed in this cell model and compared to placental tissues obtained from PE pregnancies. Seventeen PE markers were analyzed by qPCR, and the protein secretion of soluble fms-like tyrosine kinase 1 (sFlT-1) and the placenta growth factor (PlGF) was determined by ELISA. Thirteen of seventeen genes associated with angiogenesis, the renin-angiotensin system, oxidative stress, endoplasmic reticulum stress, and the inflammasome complex were susceptible to H/R and hypoxia, mimicking the expression pattern of PE tissue. In cell culture supernatants, the secretion of sFlT-1 was increased in hypoxia, while PlGF release was significantly reduced in H/R and hypoxia. In the supernatants of our cell models, the sFlT-1/PlGF ratio in hypoxia and H/R was higher than 38, which is a strong indicator for PE in clinical practice. These results suggest that our cellular models reflect important pathological processes occurring in PE and are therefore suitable as PE in vitro models
Placental Related Disorders of Pregnancy
No full textWe are pleased to present this Special Issue of International Journal of Molecular Sciences, entitled ‘Placental Related Disorders of Pregnancy’ [...
Physiological and Molecular Responses to Altered Sodium Intake in Rat Pregnancy
Full text linkBackgroundIn pregnancy, a high plasma volume maintains uteroplacental perfusion and prevents placental ischemia, a condition linked to elevated maternal blood pressure (BP). Reducing BP by increasing Na+ intake via plasma volume expansion appears contra‐intuitive. We hypothesize that an appropriate Na+ intake in pregnancy reduces maternal BP and adapts the renin‐angiotensin system in a pregnancy‐specific manner.Methods and ResultsBP was measured by implanted telemetry in Sprague‐Dawley rats before and throughout pregnancy. Pregnant and nonpregnant animals received either a normal‐salt (0.4%; NS), high‐salt (8%; HS), or low‐salt (0.01%; LS) diet, or HS (days 1–14) followed by LS (days 14–20) diet (HS/LS). Before delivery (day 20), animals were euthanized and organs collected. Food, water, and Na+ intake were monitored in metabolic cages, and urinary creatinine and Na+ were analyzed. Na+ intake and retention increased in pregnancy (NS, LS), leading to a positive Na+ balance (NS, LS). BP was stable during LS, but reduced in HS conditions in pregnancy. The renin‐angiotensin system was adapted as expected. Activating cleavage of α‐ and γ‐subunits of the renal epithelial Na+ channel and expression of‐full length medullary β‐subunits, accentuated further in all LS conditions, were upregulated in pregnancy.ConclusionsPregnancy led to Na+ retention adapted to dietary changes. HS exposure paradoxically reduced BP. Na+ uptake while only modestly linked to the renin‐angiotensin system is enhanced in the presence of posttranslational renal epithelial Na+ channel modifications. This suggests (1) storage of Na+ in pregnancy upon HS exposure, bridging periods of LS availability; and (2) that potentially non–renin‐angiotensin–related mechanisms participate in ENaC activation and consecutive Na+ retention
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