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Frontiers in Endocrinology 2019Preeclampsia is a hypertensive disorder affecting 3-5% of all pregnancies. The only curative treatment is delivery of the placenta and the pathophysiology is poorly...
Preeclampsia is a hypertensive disorder affecting 3-5% of all pregnancies. The only curative treatment is delivery of the placenta and the pathophysiology is poorly understood. Studies have demonstrated altered levels of antiangiogenic factors in patients with preeclampsia. One such factor is the antiangiogenic and antivasodilatatory peptide hormone vasoinhibin, which is higher in the circulation, urine, and amniotic fluid of women with preeclampsia. Normal pregnancy is characterized by elevated circulating prolactin and placental lactogen levels, both of which can serve as vasoinhibin precursors when they are enzymatically cleaved. A dysregulation of vasoinhibin generation during preeclampsia is indicated by higher vasoinhibin, prolactin, placental lactogen, and vasoinhibin-generating enzymes levels and activity. The present article integrates known vasoinhibin levels, effects, and signaling mechanisms to the clinical characteristics of preeclampsia to substantiate the notion that vasoinhibin dysregulation can be causally linked to the development of preeclampsia. If this view is demonstrated, assessment of vasoinhibin levels and regulation of its activity could help estimate the risk of preeclampsia and improve its treatment.
PubMed: 31998232
DOI: 10.3389/fendo.2019.00893 -
Journal of Biological Regulators and... 2019
Topics: Chromatography, Liquid; Diabetes, Gestational; Female; Human Growth Hormone; Humans; Placenta; Placental Lactogen; Pregnancy; Tandem Mass Spectrometry
PubMed: 31842532
DOI: 10.23812/19-366-L -
Journal of Diabetes Research 2019Insulin resistance changes over time during pregnancy, and in the last half of the pregnancy, insulin resistance increases considerably and can become severe, especially... (Review)
Review
Insulin resistance changes over time during pregnancy, and in the last half of the pregnancy, insulin resistance increases considerably and can become severe, especially in women with gestational diabetes and type 2 diabetes. Numerous factors such as placental hormones, obesity, inactivity, an unhealthy diet, and genetic and epigenetic contributions influence insulin resistance in pregnancy, but the causal mechanisms are complex and still not completely elucidated. In this review, we strive to give an overview of the many components that have been ascribed to contribute to the insulin resistance in pregnancy. Knowledge about the causes and consequences of insulin resistance is of extreme importance in order to establish the best possible treatment during pregnancy as severe insulin resistance can result in metabolic dysfunction in both mother and offspring on a short as well as long-term basis.
Topics: Adipokines; Chorionic Gonadotropin; Cytokines; Diabetes, Gestational; Diet; Epigenesis, Genetic; Estradiol; Exosomes; Female; Gastrointestinal Microbiome; Genetic Predisposition to Disease; Gestational Age; Growth Hormone; Humans; Hydrocortisone; Insulin Resistance; Obesity, Maternal; Placenta; Placental Hormones; Placental Lactogen; Polycystic Ovary Syndrome; Pregnancy; Progesterone; Prolactin; Sedentary Behavior
PubMed: 31828161
DOI: 10.1155/2019/5320156 -
Scientific Reports Nov 2019Advanced maternal age is associated with an increased risk of pregnancy complications. It programmes sex-specific cardiovascular dysfunction in rat offspring, however...
Advanced maternal age is associated with an increased risk of pregnancy complications. It programmes sex-specific cardiovascular dysfunction in rat offspring, however the intrauterine mechanisms involved remain unknown. This study in the rat assessed the impact of advanced maternal age on placental phenotype in relation to the growth of female and male fetuses. We show that relative to young (3-4 months) dams, advanced maternal age (9.5-10 months) compromises growth of both female and male fetuses but affects the placental phenotype sex-specifically. In placentas from aged versus young dams, the size of the placental transport and endocrine zones were increased and expression of Igf2 (+41%) and placental lactogen (Prl3b1: +59%) genes were upregulated in female, but not male fetuses. Placental abundance of IGF2 protein also decreased in the placenta of males only (-95%). Moreover, in placentas from aged versus young dams, glucocorticoid metabolism (11β-hsd2: +63% and 11β-hsd1: -33%) was higher in females, but lower in males (11β-hsd2: -50% and 11β-hsd1: unaltered). There was however, no change in the placental abundance of 11β-HSD2 protein in aged versus young dams regardless of fetal sex. Levels of oxidative stress in the placenta were increased in female and male fetuses (+57% and +90%, respectively) and apoptosis increased specifically in the placenta of males from aged rat dams (+700%). Thus, advanced maternal age alters placental phenotype in a sex-specific fashion. These sexually-divergent changes may play a role in determining health outcomes of female and male offspring of aged mothers.
Topics: Animals; Female; Fetal Development; Fetal Growth Retardation; Male; Maternal Age; Phenotype; Placenta; Pregnancy; Rats; Rats, Sprague-Dawley; Sex Factors
PubMed: 31780670
DOI: 10.1038/s41598-019-53199-x -
Veterinary Immunology and... Nov 2019Previous work carried out to characterise different immune cells in ruminant placentas found strong CD79 nuclear labelling in cells histologically resembling trophoblast...
Previous work carried out to characterise different immune cells in ruminant placentas found strong CD79 nuclear labelling in cells histologically resembling trophoblast cells. In the attempt to characterize this cell population, placentomes collected from cattle, sheep and water buffaloes were examined by immunohistochemistry with single and double labelling using monoclonal antibodies (mAb) against B lymphocytes and trophoblast cells. Most CD79 + cells co-expressed placental lactogen or cytokeratin and were CD21 and MHC class II negative strongly suggesting they do not have a B cell origin. However, a potential immunological role of these cells cannot be ruled out and it is currently unknown if the findings described may have an impact on physiological knowledge, health, and or diseases pathogenesis in ruminants.
Topics: Animals; Antibodies; Antibodies, Monoclonal; B-Lymphocytes; CD79 Antigens; Cattle; Female; Immunohistochemistry; Paraffin Embedding; Placenta; Pregnancy; Ruminants; Sheep; Trophoblasts
PubMed: 31569033
DOI: 10.1016/j.vetimm.2019.109942 -
Indian Journal of Clinical Biochemistry... Jul 2019The most preferred antenatal screening test is first trimester dual test which has a detection rate of 95% for foetal chromosomal anomaly. Maternal serum free β human...
The most preferred antenatal screening test is first trimester dual test which has a detection rate of 95% for foetal chromosomal anomaly. Maternal serum free β human chorionic gonadotropin (free β hCG) and pregnancy associated plasma protein A are used in first trimester dual test along with maternal demographic and foetal sonographic indices to calculate risk for foetal aneuploidy. Human placental lactogen is a placental hormone that is present in maternal serum only during pregnancy and its level rises in relation to the growth of the foetus and placenta. The objectives of this study was to measure and correlate maternal serum hPL with free β hCG, maternal age, maternal age related risk ratio and calculated risk ratio of first trimester screening. After obtaining permission from the Institutional Ethics Committee, hPL and free β hCG were measured from the serum of 84 pregnant women aged 20-40 years in 11-13th weeks + 6 days of gestation who underwent dual test during their antenatal check-up. Independent t test, Pearson's correlation, Spearman's correlation, Mann-Whitney U test, ANOVA were used wherever appropriate. A significant positive correlation between maternal serum hPL, maternal age related aneuploidy risk ratio ( value < 0.001) and aneuploidy risk ratio at the time of delivery ( value < 0.001) was observed. Also maternal age was negatively correlated with maternal serum hPL ( value < 0.001) and positively correlated with maternal serum free β hCG ( value 0.023). A significant negative correlation between maternal serum hPL and free β hCG ( value < 0.001) was found. To conclude low level of maternal serum hPL in advanced maternal age may reflect decreased functional syncytiotrophoblast mass which may predispose to adverse pregnancy outcome. As chance of baby born with chromosomal anomaly is known to increase with advancing maternal age, hPL may have role in first trimester screening.
PubMed: 31391722
DOI: 10.1007/s12291-018-0750-1 -
Placenta Jul 2019The wildebeest is a populous African ungulate, but despite its wide distribution within that continent few reports exist on the structure and endocrine functions of its...
INTRODUCTION
The wildebeest is a populous African ungulate, but despite its wide distribution within that continent few reports exist on the structure and endocrine functions of its placenta.
METHODS
The pregnant uteri of 43 Blue Wildebeest estimated to be at less than 70 days of the 8 month gestation period were examined grossly and histologically.
RESULTS AND DISCUSSION
The cervix divided into left and right components which eliminated any connection between the uterine horns and limited conceptus development and placentation to the single ipsilateral horn. The placenta was typically ruminant synepitheliochorial macrocotyledonary with numerous flat placentomes developing in the gravid horn. Appreciable quantities of exocrine secretion were accumulated in the lumen of both gravid and non-gravid uterine horns and proliferation of the trophoblast into presumptive villi was evident between the placentomes. The single corpus luteum of pregnancy persisted unchanged during the period of gestation monitored and the mononuclear trophoblast cells of the intercotyledonary, but not the cotyledonary, allantochorion stained strongly for 3-β hydroxysteroid dehydrogenase indicating their likely secretion of progesterone. The binucleate trophoblast cells stained positively with antisera raised against placenta-associated glycoprotein and bovine placental lactogen. Neither the maternal corpus luteum or the allantochorion showed immunohistochemical staining for cytochrome P450 aromatase.
Topics: Animals; Antelopes; Female; Placenta; Placentation; Pregnancy; Uterus
PubMed: 31174626
DOI: 10.1016/j.placenta.2019.05.008 -
The Cochrane Database of Systematic... May 2019Stillbirth affects 2.6 million pregnancies worldwide each year. Whilst the majority of cases occur in low- and middle-income countries, stillbirth remains an important... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Stillbirth affects 2.6 million pregnancies worldwide each year. Whilst the majority of cases occur in low- and middle-income countries, stillbirth remains an important clinical issue for high-income countries (HICs) - with both the UK and the USA reporting rates above the mean for HICs. In HICs, the most frequently reported association with stillbirth is placental dysfunction. Placental dysfunction may be evident clinically as fetal growth restriction (FGR) and small-for-dates infants. It can be caused by placental abruption or hypertensive disorders of pregnancy and many other disorders and factorsPlacental abnormalities are noted in 11% to 65% of stillbirths. Identification of FGA is difficult in utero. Small-for-gestational age (SGA), as assessed after birth, is the most commonly used surrogate measure for this outcome. The degree of SGA is associated with the likelihood of FGR; 30% of infants with a birthweight < 10th centile are thought to be FGR, while 70% of infants with a birthweight < 3rd centile are thought to be FGR. Critically, SGA is the most significant antenatal risk factor for a stillborn infant. Correct identification of SGA infants is associated with a reduction in the perinatal mortality rate. However, currently used tests, such as measurement of symphysis-fundal height, have a low reported sensitivity and specificity for the identification of SGA infants.
OBJECTIVES
The primary objective was to assess and compare the diagnostic accuracy of ultrasound assessment of fetal growth by estimated fetal weight (EFW) and placental biomarkers alone and in any combination used after 24 weeks of pregnancy in the identification of placental dysfunction as evidenced by either stillbirth, or birth of a SGA infant. Secondary objectives were to investigate the effect of clinical and methodological factors on test performance.
SEARCH METHODS
We developed full search strategies with no language or date restrictions. The following sources were searched: MEDLINE, MEDLINE In Process and Embase via Ovid, Cochrane (Wiley) CENTRAL, Science Citation Index (Web of Science), CINAHL (EBSCO) with search strategies adapted for each database as required; ISRCTN Registry, UK Clinical Trials Gateway, WHO International Clinical Trials Portal and ClinicalTrials.gov for ongoing studies; specialist abstract and conference proceeding resources (British Library's ZETOC and Web of Science Conference Proceedings Citation Index). Search last conducted in Ocober 2016.
SELECTION CRITERIA
We included studies of pregnant women of any age with a gestation of at least 24 weeks if relevant outcomes of pregnancy (live birth/stillbirth; SGA infant) were assessed. Studies were included irrespective of whether pregnant women were deemed to be low or high risk for complications or were of mixed populations (low and high risk). Pregnancies complicated by fetal abnormalities and multi-fetal pregnancies were excluded as they have a higher risk of stillbirth from non-placental causes. With regard to biochemical tests, we included assays performed using any technique and at any threshold used to determine test positivity.
DATA COLLECTION AND ANALYSIS
We extracted the numbers of true positive, false positive, false negative, and true negative test results from each study. We assessed risk of bias and applicability using the QUADAS-2 tool. Meta-analyses were performed using the hierarchical summary ROC model to estimate and compare test accuracy.
MAIN RESULTS
We included 91 studies that evaluated seven tests - blood tests for human placental lactogen (hPL), oestriol, placental growth factor (PlGF) and uric acid, ultrasound EFW and placental grading and urinary oestriol - in a total of 175,426 pregnant women, in which 15,471 pregnancies ended in the birth of a small baby and 740 pregnancies which ended in stillbirth. The quality of included studies was variable with most domains at low risk of bias although 59% of studies were deemed to be of unclear risk of bias for the reference standard domain. Fifty-three per cent of studies were of high concern for applicability due to inclusion of only high- or low-risk women.Using all available data for SGA (86 studies; 159,490 pregnancies involving 15,471 SGA infants), there was evidence of a difference in accuracy (P < 0.0001) between the seven tests for detecting pregnancies that are SGA at birth. Ultrasound EFW was the most accurate test for detecting SGA at birth with a diagnostic odds ratio (DOR) of 21.3 (95% CI 13.1 to 34.6); hPL was the most accurate biochemical test with a DOR of 4.78 (95% CI 3.21 to 7.13). In a hypothetical cohort of 1000 pregnant women, at the median specificity of 0.88 and median prevalence of 19%, EFW, hPL, oestriol, urinary oestriol, uric acid, PlGF and placental grading will miss 50 (95% CI 32 to 68), 116 (97 to 133), 124 (108 to 137), 127 (95 to 152), 139 (118 to 154), 144 (118 to 161), and 144 (122 to 161) SGA infants, respectively. For the detection of pregnancies ending in stillbirth (21 studies; 100,687 pregnancies involving 740 stillbirths), in an indirect comparison of the four biochemical tests, PlGF was the most accurate test with a DOR of 49.2 (95% CI 12.7 to 191). In a hypothetical cohort of 1000 pregnant women, at the median specificity of 0.78 and median prevalence of 1.7%, PlGF, hPL, urinary oestriol and uric acid will miss 2 (95% CI 0 to 4), 4 (2 to 8), 6 (6 to 7) and 8 (3 to 13) stillbirths, respectively. No studies assessed the accuracy of ultrasound EFW for detection of pregnancy ending in stillbirth.
AUTHORS' CONCLUSIONS
Biochemical markers of placental dysfunction used alone have insufficient accuracy to identify pregnancies ending in SGA or stillbirth. Studies combining U and placental biomarkers are needed to determine whether this approach improves diagnostic accuracy over the use of ultrasound estimation of fetal size or biochemical markers of placental dysfunction used alone. Many of the studies included in this review were carried out between 1974 and 2016. Studies of placental substances were mostly carried out before 1991 and after 2013; earlier studies may not reflect developments in test technology.
Topics: Female; Fetal Development; Fetal Growth Retardation; Humans; Infant, Newborn; Infant, Small for Gestational Age; Perinatal Mortality; Placenta; Pregnancy; Pregnancy Outcome; Stillbirth; Ultrasonography, Prenatal
PubMed: 31087568
DOI: 10.1002/14651858.CD012245.pub2 -
Reproduction, Fertility, and Development May 2019In order to help elucidate the process of epiblast and trophoblast cell differentiation in bovine embryos invitro, we attempted to develop a suitable culture medium to...
In order to help elucidate the process of epiblast and trophoblast cell differentiation in bovine embryos invitro, we attempted to develop a suitable culture medium to allow extended embryo culture. Day 7 bovine blastocysts developed in conventional medium were cultured further in embryonic stem cell medium with or without leukaemia inhibitory factor (LIF) until Day 23. At Day 14, the expression of octamer-binding transcription factor 3/4 (OCT3/4) and VIMENTIN was significantly higher in embryos cultured with than without LIF, but embryonic disc formation was not observed. Although expression of SRY (sex determining region Y)-box 17 (SOX17) mRNA was significantly lower in Day 14 embryos cultured with and without LIF than in invivo embryos, hypoblast cells formed just inside the trophoblast cells of the invitro-cultured embryos. On Day 23, expression of placental lactogen (PL) and prolactin-related protein 1 (PRP1) was not affected by LIF in invitro-cultured embryos, levels of both genes were significantly lower in the invitro than invivo embryos. Similar to invivo embryos, binucleate cell clusters seen in Day 23invitro-cultured embryos were composed of PL-negative and -positive cells. These results suggest that our culture system partially reproduced the differentiation process of trophoblast cells invivo.
Topics: Animals; Cattle; Cell Differentiation; Culture Media; Embryo Culture Techniques; Embryo, Mammalian; Embryonic Development; Embryonic Stem Cells; Leukemia Inhibitory Factor; Octamer Transcription Factor-3; Trophoblasts; Vimentin
PubMed: 31030728
DOI: 10.1071/RD18343 -
Frontiers in Endocrinology 2019
PubMed: 31024452
DOI: 10.3389/fendo.2019.00214