Following our first Special Issue, we are pleased to present this Special Issue in the International Journal of Molecular Sciences entitled ‘Placental Related Disorders of Pregnancy 2 ...
Placental Related Disorders of Pregnancy Lee, Eun D; Mistry, Hiten D
International journal of molecular sciences,
03/2022, Letnik:
23, Številka:
7
Journal Article
Recenzirano
Odprti dostop
We are pleased to present this Special Issue of
, entitled 'Placental Related Disorders of Pregnancy' ....
Selenium in reproductive health Mistry, Hiten D., PhD; Broughton Pipkin, Fiona, DPhil, FRCOG ad eundem; Redman, Christopher W.G., MD, FCRP, FRCOG ...
American journal of obstetrics and gynecology,
2012, 2012-Jan, 2012-01-00, 20120101, Letnik:
206, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Selenium is an essential trace element of importance to human biology and health. Increasing evidence suggests that this mineral plays an important role in normal growth and reproduction in animals ...and humans, and selenium supplementation is now recommended as part of public health policy in geographical areas with severe selenium deficiency in soil. This review addresses the biological functions of selenium followed by a detailed review of associations between selenium status and reproductive health. In many countries, selenium dietary intake falls below the recommended nutrient intakes and is inadequate to support maximal expression of the selenoenzymes. Numerous reports implicate selenium deficiency in several reproductive and obstetric complications including male and female infertility, miscarriage, preeclampsia, fetal growth restriction, preterm labor, gestational diabetes, and obstetric cholestasis. Currently, there is inadequate information from the available small intervention studies to inform public health strategies. Larger intervention trials are required to reinforce or refute a beneficial role of selenium supplementation in disorders of reproductive health.
Trace elements such as selenium and zinc are vital components of many enzymes, including endogenous antioxidants, and can interact with each other. Women with pre-eclampsia, the hypertensive disease ...of pregnancy, have been reported as having changes in some individual antioxidant trace elements during pregnancy, which are related to maternal and fetal mortality and morbidity. We hypothesised that examination of the three compartments of (a) maternal plasma and urine, (b) placental tissue and (c) fetal plasma in normotensive and hypertensive pregnant women would allow identification of biologically significant changes and interactions in selenium, zinc, manganese and copper. Furthermore, these would be related to changes in the angiogenic markers, placental growth factor (PlGF) and Soluble Fms-Like Tyrosine Kinase-1 (sFlt-1) concentrations. Venous plasma and urine were collected from healthy non-pregnant women (n = 30), normotensive pregnant controls (n = 60) and women with pre-eclampsia (n = 50) in the third trimester. Where possible, matched placental tissue samples and umbilical venous (fetal) plasma were also collected. Antioxidant micronutrient concentrations were measured by inductively coupled plasma mass-spectrometry. Urinary levels were normalised to creatinine concentration. Plasma active PlGF and sFlt-1 concentrations were measured by ELISA. Maternal plasma selenium, zinc and manganese were all lower in women with pre-eclampsia (
< 0.05), as were fetal plasma selenium and manganese (
< 0.05 for all); maternal urinary concentrations were lower for selenium and zinc (
< 0.05). Conversely, maternal and fetal plasma and urinary copper concentrations were higher in women with pre-eclampsia (
< 0.05). Differences in placental concentrations varied, with lower overall levels of selenium and zinc (
< 0.05) in women with pre-eclampsia. Maternal and fetal PlGF were lower and sFlt-1 higher in women with pre-eclampsia; maternal plasma zinc was positively correlated with maternal plasma sFlt-1 (
< 0.05). Because of perceptions that early- and late-onset pre-eclampsia have differing aetiologies, we subdivided maternal and fetal data accordingly. No major differences were observed, but fetal sample sizes were small following early-onset. Disruption in these antioxidant micronutrients may be responsible for some of the manifestations of pre-eclampsia, including contributing to an antiangiogenic state. The potential benefits of mineral supplementation, in women with deficient intakes, during pregnancy to reduce pre-eclampsia remain an important area for experimental and clinical research.
Preeclampsia (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.
This study provides a comprehensive overview of disrupted cholesterol homeostasis pathways in the pregnancy disorder preeclampsia. Additionally, we investigated a cell model designed to simulate this disorder by inducing continuous and intermittent hypoxic episodes. The graphical illustrates the examined pathways, which include cholesterol biosynthesis, conversion to progesterone, intracellular storage via esterification, and cholesterol transport. Moreover, the consequences of prolonged exposure to hypoxia on the generation of reactive oxygen species and gene regulatory processes are outlined.
Oxidative stress is widely implicated in failed reproductive performance, including infertility, miscarriage, diabetes-related congenital malformations, and preeclampsia. Maternal obesity is a strong ...risk factor for preeclampsia, and in a recent study we observed oxidative stress in the oocytes of obese animals before pregnancy as well as in early-stage embryos. This adds to the growing evidence that investigators need to focus more on the preconceptual period in efforts to prevent pregnancy disorders, including those related to oxidative stress. Our research has also focused on the role of free radicals and antioxidant capacity in preeclampsia. By measuring markers of lipid peroxidation and antioxidant capacity, we obtained unequivocal evidence for oxidative stress in this disorder. Partial failure of the process of placentation has been implicated, and recent findings suggest that ischemia-reperfusion in the placenta may contribute to oxidative stress in trophoblasts. Endoplasmic reticulum stress in the placenta may also play a role. Randomized controlled trials have been conducted by our group as well as others to determine whether early supplementation with vitamins C and E in women at risk of preeclampsia is beneficial, but these trials have shown no evidence that these supplements can prevent preeclampsia. Whether this indicates that an inappropriate antioxidant strategy was used or supplementation was administered too late in gestation to be beneficial is not known. Other potential approaches for preventing preeclampsia through amelioration of oxidative stress include the use of supplements in the preconceptual period, selenium supplements, antiperoxynitrite strategies, and statins.
The 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.
Preeclampsia is pregnancy-specific, affecting 2% to 7% of women, and is a leading cause of perinatal and maternal morbidity and mortality. Preeclampsia may also predispose the fetus to increased ...risks of adult cardiovascular disease. Selenium, acting through the selenoprotein glutathione peroxidases, has critical roles in regulating antioxidant status. Recent reports implicate poor maternal selenium status as a nutritional factor predisposing the mother to preeclampsia but the fetus and placenta have not been studied in tandem. Measurement of selenium concentrations, expression, and activity levels of glutathione peroxidase and markers of oxidative stress were performed on maternal and umbilical venous blood samples or the placenta from 27 normal pregnant, 25 preeclamptic, and 22 healthy age-matched nonpregnant women. The results of this study revealed highly significant reductions in serum selenium concentrations and plasma glutathione peroxidase activity in pregnancy per se compared to nonpregnant controls. Moreover, these levels were further decreased in the preeclamptic mothers and babies compared to normal pregnancies. Umbilical venous selenium was particularly low (42.1+/-11.8 and 29.0+/-9.9 microg/L; mean+/-SD; P<0.05). Both mother and baby had significantly increased levels of markers for oxidative stress in the preeclamptic group. The placental glutathione peroxidase activity and immunohistochemical staining were also reduced in the preeclampsia placentae. Oxidative stress associated with preeclampsia may be a consequence of reduced antioxidant defense pathways specifically involving glutathione peroxidases, perhaps linked to reduced selenium availability. Reduced glutathione peroxidases could be associated with increased generation of toxic lipid peroxides contributing to the endothelial dysfunction and hypertension of preeclampsia.
Women of reproductive age are a group of particular concern with regards to vaccine uptake, related to their unique considerations of menstruation, fertility, and pregnancy. To obtain vaccine uptake ...data specific to this group, we obtained vaccine surveillance data from the Office for National Statistics, linked with COVID-19 vaccination status from the National Immunisation Management Service, England, from 8 Dec 2020 to 15 Feb 2021; data from 13,128,525 such women at population-level, were clustered by age (18-29, 30-39, and 40-49 years), self-defined ethnicity (19 UK government categories), and index of multiple deprivation (IMD, geographically-defined IMD quintiles). Here we show that among women of reproductive age, older age, White ethnicity and being in the least-deprived index of multiple deprivation are each independently associated with higher vaccine uptake, for first and second doses; however, ethnicity exerts the strongest influence (and IMD the weakest). These findings should inform future vaccination public messaging and policy.
Endoplasmic reticulum resident protein 44 (ERp44) is a zinc-metalloprotein, regulating Endoplasmic reticulum aminopeptidase 1 (ERAP1) and Angiotensin II (Ang II). We explored placental ERp44 ...expression and components of the renin-angiotensin-system (RAS) in pre-eclampsia (PE), correlating these to ERAP1 expression and placental zinc concentrations.
Placental tissue, taken at time of delivery in normotensive women or women with PE (n = 12/group), were analysed for ERp44, AT1R, AT2R and AT4R by qPCR. Protein ERp44 expression was measured by immunohistochemistry and compared to previously measured ERAP1 expression. Placental zinc was measured by inductively-coupled-mass-spectrometry.
ERp44 gene/protein expression were increased in PE (P < 0.05). AT1R expression was increased (P = 0.02) but AT4R decreased (P = 0.01) in PE, compared to normotensive controls. A positive association between ERp44 and AT2R expression was observed in all groups. ERp44 was negatively correlated with ERAP1 protein expression in all samples. Placental zinc concentrations were lower in women with PE (P = 0.001) and negatively associated with ERp44 gene expression.
Increased placental ERp44 could further reduce ERAP1 release in PE, potentially preventing release of Ang IV and thus lowering levels of Ang IV which consequently diminishes the possibility of counterbalancing the activity of vasoconstrictive, Ang II. The lower placental zinc may contribute to dysfunction of the ERp44/ERAP1 complex, exacerbating the hypertension in PE.
•Placental ERp44, zinc, ERAP1, and renin-angiotensin-system in pre-eclampsia.•ERp44 gene/protein and AT1R expression increased in women with pre-eclampsia.•AT4R and placental zinc concentrations decreased compared to normotensive controls.•Suggests possibility for monitoring zinc intakes in women prone to pre-eclampsia.•Zinc may regulate ERp44, ERAP1 and renin-angiotensin system functions in pregnancy.
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