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Circulation Journal : Official Journal... Dec 2021Pregnant women with a Fontan circulation have a high risk of obstetric complications, such as preterm delivery and small for gestational age (SGA), which may be affected...
BACKGROUND
Pregnant women with a Fontan circulation have a high risk of obstetric complications, such as preterm delivery and small for gestational age (SGA), which may be affected by low blood flow to the placenta and hypoxia. This study investigated placental pathology in a Fontan circulation.Methods and Results:Eighteen pregnancies in 11 women with a Fontan circulation were reviewed. Pregnancy outcomes showed 9 miscarriages and 9 live births, with 4 preterm deliveries. Five neonates were SGA (<5th percentile). Eight placentas from live births in 7 women were available for the study. Five placentas had low weight placenta for gestational age, and 7 grossly showed a chronic subchorionic hematoma. Histological examination revealed all placentas had some form of histological hypoxic lesions: maternal vascular malperfusion in 7, fetal vascular malperfusion in 1, and other hypoxia-related lesions in 8. Quantitative analyses, including immunohistochemistry (CD31, CD68, and hypoxia inducible factor-1α antibodies) and Masson's trichrome staining, were also performed and compared with 5 control placentas. Capillary density and the area of fibrosis were significantly greater in placentas from women with a Fontan circulation than in control placentas.
CONCLUSIONS
Placentas in a Fontan circulation were characterized by a high frequency of low placental weight, chronic subchorionic hematoma, and constant histological hypoxic changes, which could reflect altered maternal cardiac conditions and lead to poor pregnancy outcomes.
Topics: Child; Female; Fetal Growth Retardation; Fontan Procedure; Hematoma; Humans; Hypoxia; Infant, Newborn; Infant, Small for Gestational Age; Placenta; Pregnancy
PubMed: 34497162
DOI: 10.1253/circj.CJ-21-0133 -
Placenta Jul 2022Prolonged pregnancy describes a pregnancy that progresses beyond 42 weeks' gestation (294 days). In humans, prolonged pregnancy is associated with increasing perinatal... (Review)
Review
Prolonged pregnancy describes a pregnancy that progresses beyond 42 weeks' gestation (294 days). In humans, prolonged pregnancy is associated with increasing perinatal mortality, neonatal compromise and birth by Caesarean section. The underpinning reasons behind these increased risks are unknown; one potential explanation is reduced placental function due to ageing processes. This review describes the structural and functional changes seen in prolonged pregnancy in humans and in animal models. Prolonged pregnancies are associated with reduced placental growth, leading to an increase in fetal to placental weight ratio. Microscopic changes include aggregation of syncytiotrophoblast nuclei, reduced villous vascularity with a concomitant impairment of trophoblast transport processes (reduced pinocytosis); this is associated with increased evidence of oxidative stress, with downstream consequences including cellular senescence, autophagy and apoptosis; importantly many of these changes are similar to fetal growth restriction and pre-eclampsia. Thus, we argue that these observations provide evidence of ageing within the placenta, which may initially be adaptive but can become pathological leading to a reduction in placental function. This provides a biological basis for the increased risk of adverse outcomes observed in prolonged pregnancies. Greater insight into the effects and risks of placental ageing may be useful to guide clinicians on the management of prolonged pregnancies.
Topics: Animals; Cesarean Section; Female; Fetal Growth Retardation; Humans; Placenta; Pre-Eclampsia; Pregnancy; Pregnancy, Prolonged
PubMed: 35058067
DOI: 10.1016/j.placenta.2022.01.009 -
Genes Mar 2023Exposure to environmental stressors during pregnancy plays an important role in influencing subsequent susceptibility to certain chronic diseases through the modulation...
Exposure to environmental stressors during pregnancy plays an important role in influencing subsequent susceptibility to certain chronic diseases through the modulation of epigenetic mechanisms, including DNA methylation. Our aim was to explore the connections between environmental exposures during gestation with DNA methylation of placental cells, maternal and neonatal buccal cells by applying artificial neural networks (ANNs). A total of 28 mother-infant pairs were enrolled. Data on gestational exposure to adverse environmental factors and on mother health status were collected through the administration of a questionnaire. DNA methylation analyses at both gene-specific and global level were analyzed in placentas, maternal and neonatal buccal cells. In the placenta, the concentrations of various metals and dioxins were also analyzed. Analysis of ANNs revealed that suboptimal birth weight is associated with placental methylation, maternal stress during pregnancy with methylation levels of and in placentas and mother's buccal DNA, respectively, and exposure to air pollutants with maternal methylation. Associations were also observed between placental concentrations of lead, chromium, cadmium and mercury with methylation levels of in placentas, in maternal buccal cells and placentas, in neonatal buccal cells, and in maternal buccal cells. Furthermore, dioxin concentrations were associated with placental , neonatal and maternal gene methylation levels. Current results suggest that exposure of pregnant women to environmental stressors during pregnancy could induce aberrant methylation levels in genes linked to several pathways important for embryogenesis in both the placenta, potentially affecting foetal development, and in the peripheral tissues of mothers and infants, potentially providing peripheral biomarkers of environmental exposure.
Topics: Infant, Newborn; Infant; Humans; Female; Pregnancy; Placenta; DNA Methylation; Mothers; Mouth Mucosa; Epigenesis, Genetic
PubMed: 37107594
DOI: 10.3390/genes14040836 -
Placenta Sep 2019Fetal growth restriction (FGR) is a major cause of perinatal morbidity and mortality. Identifying which pregnancies are at risk of FGR facilitates enhanced surveillance... (Review)
Review
Fetal growth restriction (FGR) is a major cause of perinatal morbidity and mortality. Identifying which pregnancies are at risk of FGR facilitates enhanced surveillance and early delivery before fetal demise can ensue. However, existing risk stratification strategies yield an unacceptably low detection rate. A robust and reliable first trimester screening test for FGR would not only enable high-risk women to be appropriately monitored but would facilitate future trials for possible interventions to enhance fetal growth. Both the volume and vascularity of the first trimester placenta has been demonstrated to be linked to adverse pregnancy outcomes including FGR and pre-eclampsia. The investigation of novel ultrasound markers for FGR are discussed along with the development of methods for fully automatic placental volume estimation which has the potential for use as part of a multi-variable population-based screening test.
Topics: Female; Fetal Development; Humans; Organ Size; Placenta; Placentation; Pregnancy; Pregnancy Trimester, First; Ultrasonography, Prenatal
PubMed: 31279487
DOI: 10.1016/j.placenta.2019.06.379 -
International Journal of Molecular... May 2022Placenta accreta spectrum (PAS) accounts for 7% of maternal mortality and is associated with intraoperative and postoperative morbidity caused by massive blood loss,...
Placenta accreta spectrum (PAS) accounts for 7% of maternal mortality and is associated with intraoperative and postoperative morbidity caused by massive blood loss, infection, and adjacent organ damage. The aims of this study were to identify the protein biomarkers of PAS and to further explore their pathogenetic roles in PAS. For this purpose, we collected five placentas from pregnant subjects with PAS complications and another five placentas from normal pregnancy (NP) cases. Then, we enriched protein samples by specifically isolating the trophoblast villous, deeply invading into the uterine muscle layer in the PAS patients. Next, fluorescence-based two-dimensional difference gel electrophoresis (2D-DIGE) and MALDI-TOF/MS were used to identify the proteins differentially abundant between PAS and NP placenta tissues. As a result, nineteen spots were determined as differentially abundant proteins, ten and nine of which were more abundant in PAS and NP placenta tissues, respectively. Then, specific validation with western blot assay and immunohisto/cytochemistry (IHC) assay confirmed that heat shock 70 kDa protein 4 (HSPA4) and chorionic somatomammotropin hormone (CSH) were PAS protein biomarkers. Further tube formation assays demonstrated that HSPA4 promoted the in vitro angiogenesis ability of vessel endothelial cells, which is consistent with the in vivo scenario of PAS complications. In this study, we not only identified PAS protein biomarkers but also connected the promoted angiogenesis with placenta invasion, investigating the pathogenetic mechanism of PAS.
Topics: Biomarkers; Cesarean Section; Endothelial Cells; Female; HSP110 Heat-Shock Proteins; Humans; Placenta; Placenta Accreta; Pregnancy
PubMed: 35628491
DOI: 10.3390/ijms23105682 -
Proceedings of the National Academy of... Dec 2023The placenta serves as the interface between the mother and fetus, facilitating the exchange of gases and nutrients between their separate blood circulation systems....
The placenta serves as the interface between the mother and fetus, facilitating the exchange of gases and nutrients between their separate blood circulation systems. Trophoblasts in the placenta play a central role in this process. Our current understanding of mammalian trophoblast development relies largely on mouse models. However, given the diversification of mammalian placentas, findings from the mouse placenta cannot be readily extrapolated to other mammalian species, including humans. To fill this knowledge gap, we performed CRISPR knockout screening in human trophoblast stem cells (hTSCs). We targeted genes essential for mouse placental development and identified more than 100 genes as critical regulators in both human hTSCs and mouse placentas. Among them, we further characterized in detail two transcription factors, DLX3 and GCM1, and revealed their essential roles in hTSC differentiation. Moreover, a gene function-based comparison between human and mouse trophoblast subtypes suggests that their relationship may differ significantly from previous assumptions based on tissue localization or cellular function. Notably, our data reveal that hTSCs may not be analogous to mouse TSCs or the extraembryonic ectoderm (ExE) in which in vivo TSCs reside. Instead, hTSCs may be analogous to progenitor cells in the mouse ectoplacental cone and chorion. This finding is consistent with the absence of ExE-like structures during human placental development. Our data not only deepen our understanding of human trophoblast development but also facilitate cross-species comparison of mammalian placentas.
Topics: Humans; Pregnancy; Mice; Female; Animals; Placentation; Placenta; Clustered Regularly Interspaced Short Palindromic Repeats; Trophoblasts; Cell Differentiation; Stem Cells; Mammals
PubMed: 38085778
DOI: 10.1073/pnas.2311372120 -
American Journal of Obstetrics and... Mar 2021The placenta plays an important role in the modulation of pregnancy immunity; however, there is no consensus regarding the existence of a placental microbiome in healthy...
BACKGROUND
The placenta plays an important role in the modulation of pregnancy immunity; however, there is no consensus regarding the existence of a placental microbiome in healthy full-term pregnancies.
OBJECTIVE
This study aimed to investigate the existence and origin of a placental microbiome.
STUDY DESIGN
A cross-sectional study comparing samples (3 layers of placental tissue, amniotic fluid, vernix caseosa, and saliva, vaginal, and rectal samples) from 2 groups of full-term births: 50 women not in labor with elective cesarean deliveries and 26 with vaginal deliveries. The comparisons were performed using polymerase chain reaction amplification and DNA sequencing techniques and bacterial culture experiments.
RESULTS
There were no significant differences regarding background characteristics between women who delivered by elective cesarean and those who delivered vaginally. Quantitative measurements of bacterial content in all 3 placental layers (quantitative polymerase chain reaction of the 16S ribosomal RNA gene) did not show any significant difference among any of the sample types and the negative controls. Here, 16S ribosomal RNA gene sequencing of the maternal side of the placenta could not differentiate between bacteria in the placental tissue and contamination of the laboratory reagents with bacterial DNA. Probe-specific quantitative polymerase chain reaction for bacterial taxa suspected to be present in the placenta could not detect any statistically significant difference between the 2 groups. In bacterial cultures, substantially more bacteria were observed in the placenta layers from vaginal deliveries than those from cesarean deliveries. In addition, 16S ribosomal RNA gene sequencing of bacterial colonies revealed that most of the bacteria that grew on the plates were genera typically found in human skin; moreover, it revealed that placentas delivered vaginally contained a high prevalence of common vaginal bacteria. Bacterial growth inhibition experiments indicated that placental tissue may facilitate the inhibition of bacterial growth.
CONCLUSION
We found no evidence to support the existence of a placental microbiome in our study of 76 term pregnancies, which used polymerase chain reaction amplification and sequencing techniques and bacterial culture experiments. Incidental findings of bacterial species could be due to contamination or to low-grade bacterial presence in some locations; such bacteria do not represent a placental microbiome per se.
Topics: Adult; Cross-Sectional Studies; Female; Humans; Microbiota; Middle Aged; Placenta; Pregnancy; Term Birth; Young Adult
PubMed: 32871131
DOI: 10.1016/j.ajog.2020.08.103 -
Placenta Dec 2021Gestational diabetes mellitus (GDM) is defined as diabetes with onset or first recognition during gestation. It is a common complication of pregnancy that has become... (Review)
Review
Gestational diabetes mellitus (GDM) is defined as diabetes with onset or first recognition during gestation. It is a common complication of pregnancy that has become more prevalent over the past few decades. Abnormalities in fetal growth, including increased incidence of both large and small for gestational age babies, suggest placental dysfunction. The major goal of this scoping review is to determine what is known about abnormalities in placentas delivered from GDM pregnancies, and how early in gestation these abnormalities arise. A secondary goal is to review to what extent other selected factors, in particular obesity, have been found to influence or modify the reported effects of GDM on placental development, and whether these are considered in the study of GDM placentas. PubMed and Scopus databases were searched using the key terms: "gestational diabetes AND (woman OR human) AND placenta AND (ultrasound OR ultrastructure OR imaging OR histology OR pathology). Studies of gross morphology and histoarchitecture in placentas delivered from GDM pregnancies consistently report increased placental size, villous immaturity and a range of vascular lesions when compared to uncomplicated pregnancies. In contrast, a small number of ultrasound studies have examined placental development in GDM pregnancies in the second, and especially, the first trimester. Relatively few studies have analyzed interactions with maternal BMI, but these do suggest that it may play a role in placental abnormalities. Further examination of placental development early in pregnancy is needed to understand when it becomes disrupted in GDM, as a first step to identifying the underlying causes.
Topics: Diabetes, Gestational; Female; Humans; Placenta; Pregnancy; Ultrasonography, Prenatal
PubMed: 33958235
DOI: 10.1016/j.placenta.2021.04.005 -
FASEB Journal : Official Publication of... Mar 2021The degree that maternal glycemia affects placental metabolism of trophoblast cell types [cytotrophoblast (CTB) and syncytiotrophoblast (SCT)] in pregnant persons with...
The degree that maternal glycemia affects placental metabolism of trophoblast cell types [cytotrophoblast (CTB) and syncytiotrophoblast (SCT)] in pregnant persons with gestational diabetes mellitus (GDM) is unknown. We tested the hypotheses that (a) hyperglycemia suppresses the metabolic rates of CTB and SCT; and (b) low placental metabolic activity from GDM placentas is due to decreased oxygen consumption of CTB. Trophoblast cells isolated from GDM and non-GDM term placentas were cultured for 8-hour (CTB) and following syncytialization at 72-hour (SCT) in 5 mM of glucose or 25 mM of glucose. Oxygen consumption rates, glycolysis, ATP levels, and lipid droplet morphometries were determined in CTB and SCT. In CTB from GDM placentas compared to control CTB: (a) oxidative phosphorylation was decreased by 44% (41.8 vs 74.2 pmol O /min/100 ng DNA, P = .002); (b) ATP content was 39% lower (1.1 × 10 vs 1.8 × 10 nM/ng DNA, P = .046); and (c) lipid droplets were two times larger (31.0 vs 14.4 µm /cell, P < .001) and 1.7 times more numerous (13.5 vs 7.9 lipid droplets/cell, P < .001). Hyperglycemia suppressed CTB glycolysis by 55%-60% (mean difference 20.4 [GDM, P = .008] and 15.4 [non-GDM, P = .029] mpH/min/100 ng DNA). GDM SCT was not metabolically different from non-GDM SCT. However, GDM SCT had significantly decreased expression of genes associated with differentiation including hCG, GCM1, and syncytin-1. We conclude that suppressed metabolic activity by the GDM placenta is attributable to metabolic dysfunction of CTB, not SCT. Critical placental hormone expression and secretion are decreased in GDM trophoblasts.
Topics: Cell Differentiation; Diabetes, Gestational; Female; Glucose; Glycolysis; Humans; Hyperglycemia; Lipids; Mitochondria; Oxidative Phosphorylation; Oxygen Consumption; Placenta; Pregnancy; Trophoblasts
PubMed: 33605480
DOI: 10.1096/fj.202000326RR -
Journal of Dairy Science Apr 2021Heat stress is detrimental during gestation; however, the effects of heat stress on goat placental characteristics and kid survival remain unclear. The objective of this...
Heat stress is detrimental during gestation; however, the effects of heat stress on goat placental characteristics and kid survival remain unclear. The objective of this study was to evaluate the effects of heat stress at final gestation on cortisol concentration, placenta characteristics, and the expression of genes related to placenta. Forty-six primiparous and multiparous Saanen goats were subjected to control (CT; under a thermoneutral environment: air temperature between 12°C and 25°C and the relative humidity from 45 to 73%, n = 23) or heat stress (HS; under a climatic chamber: air temperature at 37°C and the relative humidity at 60 to 70% from 0800 to 1600 h, n = 23) from the last 60 d of pregnancy until the first colostrum suckling. The heat challenge imposed on HS goats during the prepartum period increased their rectal temperature, respiratory frequency, and cortisol levels in plasma and amniotic fluid versus CT goats. In the placenta, HS treatment also increased the expression of the HSPA1A gene. Heat-stressed goats also showed significantly lower expression of HSD11B2 and greater expression of MC2R and NR3C1 than CT goats, suggesting that heat stress decreased the effectiveness by which the HSD11B2 enzyme converts cortisol to cortisone and increased placental responsiveness to cortisol. The HS goats took longer to release the placenta with lighter placental cotyledons, and HS goats had a lower ratio between the kid's weight at birth and placenta weight than CT goats. There was no treatment effect on the kids' survival or weights at birth, but the kids from goats subjected to HS presented lesser cortisol concentration and greater mortality rates at weaning than kids from CT goats. Finally, the overexpression of HSPA1A by HS goats suggests a protective response of placenta. However, the heat stress negatively affected the placenta's expulsion length, placental cotyledons number, weight and area, the ratio between kid's weight and placenta weight, and cortisol signaling. Indeed, the upregulation of MC2R and NR3C1 and downregulation of HSD11B2 on placenta caused by heat stress were associated with greater cortisol concentrations in the amniotic fluid of HS goats. Although HS and CT kids had adequate weights and survival rate during the first weeks of life, the heat stress increased the mortality at weaning of HS kids versus CT kids, suggesting that the heat stress effect persists and can change the ability of kids to respond to weaning challenge.
Topics: Animals; Female; Goat Diseases; Goats; Heat Stress Disorders; Heat-Shock Response; Parturition; Placenta; Pregnancy
PubMed: 33551154
DOI: 10.3168/jds.2020-18301