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Antiviral Research Jul 2020The association of Zika virus infection (ZIKV) with congenital malformation and neurological sequelae brought a significant global concern. Recent studies have shown...
The association of Zika virus infection (ZIKV) with congenital malformation and neurological sequelae brought a significant global concern. Recent studies have shown that maternal viral infection leads to inflammation in the placental tissue. In this context, the antiinflammatory protein annexin 1 (ANXA1) has a major determination of the resolution of inflammation and it has been positively associated with antiparasitic activity in infected placental explants. Although these effects have been explored to some degree, ANXA1 expression and potential properties have not yet been fully elucidated in placentas infected with ZIKV. This study was conducted to evaluate the histopathology, inflammatory process and elucidate if ANXA1 were differently expressed in placentas of ZIKV-infected mothers. Three classification groups were used in this study: Neg/Neg (mother and placenta negative for the virus), Pos/Neg (infected mother, but no virus detected in placenta) and Pos/Pos (mother and placenta infected with ZIKV). ANXA1 was expressed in syncytiotrophoblast cells of all studied groups, and its expression was decreased in Pos/Neg group, which displayed also an increase of the inflammatory response, as evinced from the recruitment of inflammatory cells, increased levels of placenta cytokines, and evidence of impaired tissue repair. The presence of ZIKV in placentas of Pos/Pos group shows structural alterations, including detachment and disorganization of the trophoblastic epithelium. In summary, our results suggest that maternal infection with ZIKV, even without direct tissue infection, leads to a placental inflammatory response probably related to the modulation of ANXA1. After placental infection, structural changes - including inflammatory cells influx - are observed leading to placental dysfunction and reduced fetal weight. Our study sheds additional light on the outcomes of ZIKV infection in trophoblast and reveals a potential involvement of ANXA1 in the placental biology.
Topics: Adult; Annexin A1; Anti-Inflammatory Agents; Cross-Sectional Studies; Female; Humans; Inflammation; Placenta; Pregnancy; Pregnancy Complications, Infectious; Trophoblasts; Young Adult; Zika Virus Infection
PubMed: 32360947
DOI: 10.1016/j.antiviral.2020.104809 -
American Journal of Perinatology Jul 2018The objective of this study was to validate estimated placental volume (EPV) across a range of gestational ages (GAs). (Observational Study)
Observational Study
OBJECTIVE
The objective of this study was to validate estimated placental volume (EPV) across a range of gestational ages (GAs).
STUDY DESIGN
Three hundred sixty-six patients from 2009 to 2011 received ultrasound scans between 11 + 0 and 38 + 6 weeks GA to assess EPV. An EPV versus GA best fit curve was generated and compared with published normative curves of EPV versus GA in a different population. A subanalysis was performed to explore the relationship between EPV and birth weight (BW).
RESULTS
Analysis of EPV versus GA revealed a parabolic curve with the following best fit equation: EPV = (0.372 GA - 0.00364 GA). EPV was weakly correlated with BW, and patients with an EPV in the bottom 50th percentile had 2.42 times the odds of having a newborn with a BW in the bottom 50th percentile (95% confidence interval: 1.27-4.68). Microscopic evaluation of two placentas corresponding to the smallest EPV outliers revealed significant placental pathology.
CONCLUSION
Placental volume increases throughout gestation and follows a predictable parabolic curve, in agreement with the existing literature. Further validation is required, but EPV may have the potential for clinical utility as a screening tool in a variety of settings.
Topics: Adolescent; Adult; Birth Weight; Female; Gestational Age; Humans; Infant, Newborn; Male; Organ Size; Placenta; Pregnancy; Prospective Studies; Ultrasonography, Prenatal; Young Adult
PubMed: 29281842
DOI: 10.1055/s-0037-1615285 -
Placenta Sep 2017A significant proportion of children born preterm will experience some level of neurodevelopmental impairment. Changes in placental function have been observed with many... (Review)
Review
A significant proportion of children born preterm will experience some level of neurodevelopmental impairment. Changes in placental function have been observed with many antenatal conditions that are risk factors for preterm birth and/or poor neurodevelopment including fetal growth restriction and in-utero inflammation. This review will highlight placental factors that have been studied to understand the underlying mechanisms and identify biomarkers that lead to poor child neurodevelopmental outcomes. These include changes in gross morphological and histopathological structure and the placental inflammatory response to prenatal infection. Further, we will describe the placenta's role as both a barrier to maternally-derived bioactive substances critical for normal fetal brain development, such as cortisol, and a source of neuroactive steroids and neurotrophins known to have critical functions in neuronal proliferation, axonal growth, myelination and the regulation of apoptosis. Finally, emerging data supporting the potential utility of novel placental biomarkers in the early prediction of poor neurodevelopmental outcome in infants born both preterm and term will be discussed. These include the assessment of genetic variants (e.g. single nucleotide polymorphisms in placental tissue) and epigenetic biomarkers (e.g. placental microRNAs and placental DNA methylation). With the placenta the key tissue regulating the fetal environment, integration of observed changes in placental function with genetic and epigenetic variations may advance our ability to predict future infant health. Ultimately, this may facilitate targeted allocation of health resources with the aim of improving lifelong neurodevelopmental capability.
Topics: Biomarkers; Child Development; Female; Humans; Infant; Neurodevelopmental Disorders; Placenta; Pregnancy; Premature Birth
PubMed: 28864022
DOI: 10.1016/j.placenta.2017.06.009 -
Journal of Hazardous Materials Apr 2019Acrylamide, a carcinogen and neurotoxic substance, recently has been discovered in various heat-treated carbohydrate-rich foods. The aim of this study was to investigate...
Acrylamide, a carcinogen and neurotoxic substance, recently has been discovered in various heat-treated carbohydrate-rich foods. The aim of this study was to investigate the effects of acrylamide exposure on placental development. Pregnant mice received acrylamide by gavage at dosages of 0, 10, and 50 mg/kg/day from gestational days (GD) 3 until GD 8 or GD 13. The results showed that acrylamide feeding significantly decreased the numbers of viable embryos and increased the numbers of resorbed embryos on GD 13. Acrylamide exposure reduced the absolute and relative weight of placentas and embryos, and inhibited the development of ectoplacental cone (EPC) and placenta, as shown by the atrophy of EPC and reduced placental area. Acrylamide markedly reduced the numbers of labyrinth vessels. Expression levels of most placental key genes such as Esx1, Hand1, and Hand2 mRNA dramatically decreased in acrylamide-treated placentas. Furthermore, acrylamide treatment inhibited proliferation and induced apoptosis of placentas, as shown by decreased Ki67-positive cells and Bcl-2 protein, and increased the expression of Bax, cleaved-caspase-3, and cleaved-caspase-8 proteins. In conclusion, our results indicated that gestational exposure to acrylamide inhibits placental development through dysregulation of placental key gene expression and labyrinth vessels, suppression of proliferation, and apoptosis induction in mice.
Topics: Acrylamide; Animals; Apoptosis; Embryonic Development; Female; Maternal-Fetal Exchange; Mice; Placenta; Placentation; Pregnancy
PubMed: 30594716
DOI: 10.1016/j.jhazmat.2018.12.061 -
BMC Pregnancy and Childbirth Jun 2020There has been debate about the existence of lymphatic vessels in placenta. Lymphatic endothelial cell (LEC) markers such as LYVE-1 and podoplanin/D2-40 have been found,...
BACKGROUND
There has been debate about the existence of lymphatic vessels in placenta. Lymphatic endothelial cell (LEC) markers such as LYVE-1 and podoplanin/D2-40 have been found, although PROX1 has not been detected. The most reliable marker for LECs is the double staining for CD31 and PROX1, which has not been performed yet.
METHODS
We studied three term placentas and dissected them into three areas: i.) basal plate area, ii.) intermediate area, and iii.) chorionic plate area. We used immunofluorescence single and double staining with antibodies against CD31, PROX1, LYVE-1, VEGFR-3, D2-40/PDPN, CD34, CCBE-1, and vimentin, as well as nested PCR, qPCR, Western blot and transmission electron microscopy (TEM).
RESULTS
At TEM level we observed structures that have previously mistakenly been interpreted as lymphatics, however, we did not find any CD31/PROX1 double-positive cells in placenta. Absence of PROX1 was also noted by nested PCR, qPCR and Western blot. Also, LEC marker VEGFR-3 was expressed only in a small number of scattered leukocytes but was absent from vessels. The LEC marker D2-40/PDPN was expressed in most stromal cells, and the LEC marker LYVE-1 was found in a considerable number of stromal cells, but not in endothelial cells, which were positive for CD31, CD34, CCBE-1 and vimentin. Additionally, vimentin was found in stromal cells.
CONCLUSIONS
Our studies clearly show absence of lymphatics in term placenta. We also show that the functional area of the mother's endometrium is not penetrated by lymphatics in term pregnancy.
Topics: Biomarkers; Endometrium; Endothelial Cells; Female; Humans; Lymphatic Vessels; Membrane Glycoproteins; Placenta; Pregnancy; Transcription Factors; Vascular Endothelial Growth Factor Receptor-3
PubMed: 32600346
DOI: 10.1186/s12884-020-03073-w -
Placenta Sep 2021Impaired placentation is an important contributing factor to intra-uterine growth restriction and pre-eclampsia in fetuses with congenital heart defects (CHD). These...
Impaired placentation is an important contributing factor to intra-uterine growth restriction and pre-eclampsia in fetuses with congenital heart defects (CHD). These pregnancy complications occur more frequently in pregnancies with fetal CHD. One of the most important factors influencing the life of children with CHD is neurodevelopmental delay, which seems to start already in utero. Delayed neurodevelopment in utero may be correlated or even (partly) explained by impaired placentation in CHD cases. This systematic review provides an overview of published literature on placental development in pregnancies with fetal CHD. A systematic search was performed and the Newcastle-Ottawa scale was used to access data quality. Primary outcomes were placenta size and weight, vascular and villous architecture, immunohistochemistry, angiogenic biomarkers and/or placental gene expression. A total of 1161 articles were reviewed and 21 studies were included. Studies including CHD with a genetic disorder or syndrome and/or multiple pregnancies were excluded. Lower placental weight and elevated rates of abnormal umbilical cord insertions were found in CHD. Cases with CHD more frequently showed microscopic placental abnormalities (i.e. abnormal villous maturation and increased maternal vascular malperfusion lesions), reduced levels of angiogenic biomarkers and increased levels of anti-angiogenic biomarkers in maternal serum and umbilical cord blood. Altered gene expression involved in placental development and fetal growth were found in maternal serum and CHD placentas. In conclusion, abnormal placentation is found in CHD. More extensive studies are needed to elucidate the contribution of impaired placentation to delayed neurodevelopment in CHD cases.
Topics: Biomarkers; Female; Fetal Development; Heart Defects, Congenital; Humans; Placenta; Placentation; Pregnancy
PubMed: 34388551
DOI: 10.1016/j.placenta.2021.07.297 -
Pathobiology : Journal of... 2021Since the outbreak of coronavirus disease 2019 (COVID-19), there has been a debate whether pregnant women are at a specific risk for COVID-19 and whether it might be...
Since the outbreak of coronavirus disease 2019 (COVID-19), there has been a debate whether pregnant women are at a specific risk for COVID-19 and whether it might be vertically transmittable through the placenta. We present a series of five placentas of SARS coronavirus 2 (SARS-CoV-2)-positive women who had been diagnosed with mild symptoms of COVID-19 or had been asymptomatic before birth. We provide a detailed histopathologic description of morphological changes accompanied by an analysis of presence of SARS-CoV-2 in the placental tissue. All placentas were term deliveries (40th and 41st gestational weeks). One SARS-CoV-2-positive patient presented with cough and dyspnoea. This placenta showed prominent lymphohistiocytic villitis and intervillositis and signs of maternal and foetal malperfusion. Viral RNA was present in both placenta tissue and the umbilical cord and could be visualized by in situ hybridization in the decidua. SARS-CoV-2 tests were negative at the time of delivery of 3/5 women, and their placentas did not show increased inflammatory infiltrates. Signs of maternal and/or foetal malperfusion were present in 100% and 40% of cases, respectively. There was no transplacental transmission to the infants. In our cohort, we can document different time points regarding SARS-CoV-2 infection. In acute COVID-19, prominent lymphohistiocytic villitis may occur and might potentially be attributable to SARS-CoV-2 infection of the placenta. Furthermore, there are histopathological signs of maternal and foetal malperfusion, which might have a relationship to an altered coagulative or microangiopathic state induced by SARS-CoV-2, yet this cannot be proven considering a plethora of confounding factors.
Topics: Adult; COVID-19; Cohort Studies; Female; Humans; Placenta; Pregnancy; SARS-CoV-2
PubMed: 32950981
DOI: 10.1159/000511324 -
Reproduction in Domestic Animals =... Jul 2019Macroscopic evaluation of the placenta is an essential post-partum examination in the alpaca and can be of special interest in case of abortion, premature birth or...
Macroscopic evaluation of the placenta is an essential post-partum examination in the alpaca and can be of special interest in case of abortion, premature birth or stillbirth. Since there are not many reference values regarding macroscopic properties of normal alpaca placentas, a small descriptive study was conducted. Only placentae from normally foaling alpaca mares, giving birth to healthy crias, after a full-term and uneventful gestation (±350 days; range 335-360 days) were taken into account (N = 11). Crias weighed (±SD) 7.7 ± 2.25 kg (range 5.5-10 kg), while the mean weight of the full-term placentas was 0.8 ± 0.19 kg, that is 10% of the bodyweight of the crias. The weight of the allantoamnion and chorion was 0.2 ± 0.07 kg and 0.5 ± 0.13 kg, respectively. The umbilical cord length was 8.8 ± 2.84 cm, and the length of the pregnant and non-pregnant uterine horns was 69.4 ± 12.77 cm and 54.5 ± 6.81 cm, respectively. The length of the corpus was 14.6 ± 4.68 cm, and the distance from the umbilicus to the corpus was 18.5 ± 6.13 cm. The tissue volume of the allantoamnion was 0.14 ± 0.079 L, and the chorionic volume was 0.37 ± 0.078 L. The surface area of the allantoamnion and the chorion was 87.6 ± 15.56 dm and 72.3 ± 9.28 dm , respectively. All placentas had small calcifications either around the umbilical cord alone or around the umbilicus and blood vessels of the pregnant uterine horn. These measurements could be used to macroscopically evaluate alpaca placentas, although more research is needed to extend our knowledge of macroscopic evaluation of normal and abnormal placentas.
Topics: Animals; Camelids, New World; Female; Placenta; Postpartum Period; Pregnancy; Umbilical Cord
PubMed: 31059204
DOI: 10.1111/rda.13453 -
PloS One 2020Gestational Diabetes Mellitus (GDM) is characterized by abnormal maternal D-glucose metabolism and altered insulin signaling. Dysregulation of thyroid hormones (TH)... (Clinical Trial)
Clinical Trial
High levels of maternal total tri-iodothyronine, and low levels of fetal free L-thyroxine and total tri-iodothyronine, are associated with altered deiodinase expression and activity in placenta with gestational diabetes mellitus.
Gestational Diabetes Mellitus (GDM) is characterized by abnormal maternal D-glucose metabolism and altered insulin signaling. Dysregulation of thyroid hormones (TH) tri-iodethyronine (T3) and L-thyroxine (T4) Hormones had been associated with GDM, but the physiopathological meaning of these alterations is still unclear. Maternal TH cross the placenta through TH Transporters and their Deiodinases metabolize them to regulate fetal TH levels. Currently, the metabolism of TH in placentas with GDM is unknown, and there are no other studies that evaluate the fetal TH from pregnancies with GDM. Therefore, we evaluated the levels of maternal TH during pregnancy, and fetal TH at delivery, and the expression and activity of placental deiodinases from GDM pregnancies. Pregnant women were followed through pregnancy until delivery. We collected blood samples during 10-14, 24-28, and 36-40 weeks of gestation for measure Thyroid-stimulating hormone (TSH), Free T4 (FT4), Total T4 (TT4), and Total T3 (TT3) concentrations from Normal Glucose Tolerance (NGT) and GDM mothers. Moreover, we measure fetal TSH, FT4, TT4, and TT3 in total blood cord at the delivery. Also, we measured the placental expression of Deiodinases by RT-PCR, western-blotting, and immunohistochemistry. The activity of Deiodinases was estimated quantified rT3 and T3 using T4 as a substrate. Mothers with GDM showed higher levels of TT3 during all pregnancy, and an increased in TSH during second and third trimester, while lower concentrations of neonatal TT4, FT4, and TT3; and an increased TSH level in umbilical cord blood from GDM. Placentae from GDM mothers have a higher expression and activity of Deiodinase 3, but lower Deiodinase 2, than NGT mothers. In conclusion, GDM favors high levels of TT3 during all gestation in the mother, low levels in TT4, FT4 and TT3 at the delivery in neonates, and increases deiodinase 3, but reduce deiodinase 2 expression and activity in the placenta.
Topics: Adult; Diabetes, Gestational; Female; Gene Expression Regulation, Enzymologic; Humans; Iodide Peroxidase; Placenta; Pregnancy; Thyroxine; Triiodothyronine; Iodothyronine Deiodinase Type II
PubMed: 33232364
DOI: 10.1371/journal.pone.0242743 -
American Journal of Perinatology May 2024Circumvallate placenta has a suggested association with adverse pregnancy outcomes (antenatal bleeding, placental abruption, preterm birth, emergency cesarean, small...
OBJECTIVE
Circumvallate placenta has a suggested association with adverse pregnancy outcomes (antenatal bleeding, placental abruption, preterm birth, emergency cesarean, small for gestational age infants, and stillbirth). The aim was to determine if prenatal diagnosis of circumvallate placenta is associated with these adverse pregnancy outcomes.
STUDY DESIGN
Pregnancies with a singleton gestation prenatally diagnosed with circumvallate placenta between January 1, 2012 and March 31, 2021 were identified. Adverse pregnancy outcomes were obtained. Rates of adverse pregnancy outcomes were compared among those with prenatally diagnosed circumvallate placentas to those without this prenatal diagnosis with a 4:1 control matched group. Pregnancies with known fetal anomalies or other placental abnormalities were excluded. Statistical analyses included Student's t-test and with < 0.05 considered significant.
RESULTS
Prenatal ultrasound findings of circumvallate placenta were seen in 179 pregnant people (0.20% of all anatomic US studies and 0.17% of all deliveries). Diagnosis was made at a mean gestational age of 19.8 ± 2.4 weeks. Adverse pregnancy outcomes were similar between groups.
CONCLUSION
Prenatal ultrasound findings of circumvallate placenta do not correlate with adverse pregnancy outcomes. Given overall good prognosis, prenatal diagnosis of circumvallate placenta may not warrant additional surveillance during pregnancy.
KEY POINTS
· The risk of prenatally diagnosed circumvallate placenta was previously unclear.. · Prenatally diagnosed circumvallate placenta is not associated with adverse pregnancy outcomes.. · No change in management may be necessary with prenatally diagnosed circumvallate placenta..
Topics: Humans; Pregnancy; Female; Ultrasonography, Prenatal; Adult; Pregnancy Outcome; Placenta; Retrospective Studies; Infant, Newborn; Gestational Age; Premature Birth; Abruptio Placentae; Case-Control Studies; Cesarean Section; Stillbirth
PubMed: 37336232
DOI: 10.1055/s-0043-1770337