-
American Journal of Physiology.... May 2012The human placenta is key to pregnancy outcome, and the elevated oxidative stress present in many complicated pregnancies contributes to placental dysfunction and... (Randomized Controlled Trial)
Randomized Controlled Trial
The human placenta is key to pregnancy outcome, and the elevated oxidative stress present in many complicated pregnancies contributes to placental dysfunction and suboptimal pregnancy outcomes. We tested the hypothesis that pomegranate juice, which is rich in polyphenolic antioxidants, limits placental trophoblast injury in vivo and in vitro. Pregnant women with singleton pregnancies were randomized at 35∼38 wk gestation to 8 oz/day of pomegranate juice or apple juice (placebo) until the time of delivery. Placental tissues from 12 patients (4 in the pomegranate group and 8 in the control group) were collected for analysis of oxidative stress. The preliminary in vivo results were extended to oxidative stress and cell death assays in vitro. Placental explants and cultured primary human trophoblasts were exposed to pomegranate juice or glucose (control) under defined oxygen tensions and chemical stimuli. We found decreased oxidative stress in term human placentas from women who labored after prenatal ingestion of pomegranate juice compared with apple juice as control. Moreover, pomegranate juice reduced in vitro oxidative stress, apoptosis, and global cell death in term villous explants and primary trophoblast cultures exposed to hypoxia, the hypoxia mimetic cobalt chloride, and the kinase inhibitor staurosporine. Punicalagin, but not ellagic acid, both prominent polyphenols in pomegranate juice, reduced oxidative stress and stimulus-induced apoptosis in cultured syncytiotrophoblasts. We conclude that pomegranate juice reduces placental oxidative stress in vivo and in vitro while limiting stimulus-induced death of human trophoblasts in culture. The polyphenol punicalagin mimics this protective effect. We speculate that antenatal intake of pomegranate may limit placental injury and thereby may confer protection to the exposed fetus.
Topics: Antioxidants; Apoptosis; Beverages; Cells, Cultured; Female; Humans; Hydrolyzable Tannins; In Vitro Techniques; Lythraceae; Oxidative Stress; Placenta; Polyphenols; Pregnancy; Trophoblasts
PubMed: 22374759
DOI: 10.1152/ajpendo.00003.2012 -
Proceedings. Biological Sciences Jan 2020The mammalian placenta is both the physical interface between mother and fetus, and the source of endocrine signals that target the maternal hypothalamus, priming...
The mammalian placenta is both the physical interface between mother and fetus, and the source of endocrine signals that target the maternal hypothalamus, priming females for parturition, lactation and motherhood. Despite the importance of this connection, the effects of altered placental signalling on the maternal brain are insufficiently studied. Here, we show that placental dysfunction alters gene expression in the maternal brain, with the potential to affect maternal behaviour. Using a cross between the house mouse and the Algerian mouse, in which hybrid placental development is abnormal, we sequenced late-gestation placental and maternal medial preoptic area transcriptomes and quantified differential expression and placenta-maternal brain co-expression between normal and hybrid pregnancies. The expression of and was significantly altered in the brains of females exposed to hybrid placentas. Most strikingly, expression patterns of placenta-specific gene families and in the brains of house mouse females carrying hybrid litters matched those of female Algerian mice, the paternal species in the cross. Our results indicate that the paternally derived placental genome can influence the expression of maternal-fetal communication genes, including placental hormones, suggesting an effect of the offspring's father on the mother's brain.
Topics: Animals; Brain; Chimera; Female; Gene Expression; Maternal Behavior; Mice; Placenta; Pregnancy
PubMed: 31937228
DOI: 10.1098/rspb.2019.2563 -
American Journal of Obstetrics and... Oct 2015Over the past quarter century it has become clear that adult onset chronic diseases like heart disease and type 2 diabetes have their roots in early development. The...
Over the past quarter century it has become clear that adult onset chronic diseases like heart disease and type 2 diabetes have their roots in early development. The report by David Barker and colleagues showing an inverse relationship between birthweight and mortality from ischemic heart disease was the first clear-cut demonstration of fetal programming. Because fetal growth depends upon the placental capacity to transport nutrients from maternal blood, it has been a suspected causative agent since the original Barker reports. Epidemiological studies have shown that placental size and shape have powerful associations with offspring disease. More recent studies have shown that maternal phenotypic characteristics, such as body mass index and height, interact with placental size and shape to predict disease with much more precision than does birthweight alone. For example, among people in the Helsinki Birth Cohort, who were born during 1924–1944, the risk for acquiring colorectal cancer increased as the placental surface became longer and more oval. Among people in whom the difference between the length and breadth of the surface exceeded 6 cm, the hazard ratio for the cancer was 2.3 (95% CI 1.2–4.7, p=0.003) compared with those in whom there was no difference. Among Finnish men, the hazard ratio for coronary heart disease was 1.07 (1.02–1.13, P =0.01) per 1% increase in the placental weight/birthweight ratio. Thus, it appears that the ratio of birthweight to placental weight, known as placental efficiency, predicts cardiovascular risk as well. Babies born with placentas at the extremes of efficiency are more vulnerable for adult onset chronic diseases. Recent evidence suggests that placental growth patterns are sex specific. Boys’ placentas are, in general, more efficient than those made by girls. Another recent discovery is that the size, shape and efficiencies of the placenta can change over years of time with very narrow confidence limits. This suggests that the growth of the placenta within a population of women is strongly affected by their nutritional environment. Even though it is known that an individual placenta can expand to improve its nutrient acquisition capacity in the first 2/3 of gestation, the mechanisms by which placentas grow in response to a specific nutritional environment are not known. Discovering those mechanisms is the task of the current generation of scientists. While it may seem obvious that good nutrition is highly important for women who are pregnant because it supports optimal placentation and fetal development, more research is needed to determine the mechanisms by which maternal nutrition, placenta growth and fetal health are related.
Topics: Animals; Birth Weight; Cardiovascular Diseases; Chorioamnionitis; Chronic Disease; Female; Fetal Development; Glucocorticoids; Humans; Male; Organ Size; Placenta; Pregnancy; Risk Factors; Stress, Physiological
PubMed: 26428494
DOI: 10.1016/j.ajog.2015.08.030 -
Frontiers in Endocrinology 2020An adequate development of the placenta includes trophoblast differentiation with the processes of trophoblast migration, invasion, cellular senescence and apoptosis...
OBJECTIVES
An adequate development of the placenta includes trophoblast differentiation with the processes of trophoblast migration, invasion, cellular senescence and apoptosis which are all crucial to establishing a successful pregnancy. Altered placental development and function lead to placental diseases such as preeclampsia (PE) which is mainly characterized by insufficient trophoblast invasion and abnormally invasive placenta (AIP) disorders (, , or which are characterized by excessive trophoblast invasion. Both of them will cause maternal and fetal morbidity/mortality. However, the etiology of these diseases is still unclear. Our previous study has shown that the matricellular protein (NOV, CCN3) induces G0/G1 cell cycle arrest, drives trophoblast cells into senescence and activates FAK and Akt kinases resulting in reduced cell proliferation and enhanced migration capability of the human trophoblast cell line SGHPL-5. The present study focuses on whether CCN3 can alter cell cycle-regulated pathways associated with trophoblast senescence and invasion activity in pathological versus gestational age-matched control placentas.
METHODS
Cell cycle regulator proteins were investigated by immunoblotting and qPCR. For localization of CCN3, p16, p21, and Cyclin D1 proteins, co-immunohistochemistry was performed.
RESULTS
In early-onset PE placentas, CCN3 was expressed at a significantly lower level compared to gestational age-matched controls. The decrease of CCN3 level is associated with an increase in p53, Cyclin E1 and pRb protein expression, whereas the level of cleaved Notch-1, p21, Cyclin D1, pFAK, pAKT, and pmTOR protein decreased. In term AIP placentas, the expression of CCN3 was significantly increased compared to matched term controls. This increase was correlated to an increase in p53, p16, p21, Cyclin D1, cleaved Notch-1, pFAK, pAkt, and pmTOR whereas pRb was significantly decreased. However, in late PE and early AIP placentas, no significant differences in CCN3, p16, p21, Cyclin D1, p53, and cleaved Notch-1 expression were found when matched to appropriate controls.
CONCLUSIONS
CCN3 expression levels are correlated to markers of cell cycle arrest oppositely in PE and AIP by activating the FAK/AKT pathway in AIP or down-regulating in PE. This may be one mechanism to explain the different pathological features of placental diseases, PE and AIP.
Topics: Adult; Biomarkers; Case-Control Studies; Cell Cycle Checkpoints; Cell Movement; Cell Proliferation; Cellular Senescence; Female; Humans; Nephroblastoma Overexpressed Protein; Placenta; Placenta Diseases; Pre-Eclampsia; Pregnancy
PubMed: 33304321
DOI: 10.3389/fendo.2020.597549 -
American Journal of Obstetrics and... Jul 2008The overtly healthy, nonpregnant uterus harbors bacteria, Mycoplasma and Ureaplasma. The extent of colonization remains elusive, as are relationships between isolated...
OBJECTIVE
The overtly healthy, nonpregnant uterus harbors bacteria, Mycoplasma and Ureaplasma. The extent of colonization remains elusive, as are relationships between isolated microorganisms, preterm labor and fetal inflammation.
STUDY DESIGN
Biopsy specimens of chorion parenchyma from 1083 placentas delivered before the beginning of the 28th week of gestation were cultured, and the placentas were examined histologically. The frequencies of individual microorganisms and groups of microorganisms were evaluated in strata of processes leading to preterm delivery, routes of delivery, gestational age, and placenta morphology.
RESULTS
Placentas delivered by cesarean section with preeclampsia had the lowest bacterial recovery rate (25%). Preterm labor had the highest rates, which decreased with increasing gestational age from 79% at 23 weeks to 43% at 27 weeks. The presence of microorganisms in placenta parenchyma was associated with the presence of neutrophils in the fetal stem vessels of the chorion or in the vessels of the umbilical cord.
CONCLUSION
The high rate of colonization appears to coincide with phenomena associated with preterm delivery and gestational age. The presence of microorganisms within placenta parenchyma is biologically important.
Topics: Adult; Cesarean Section; Female; Gestational Age; Humans; Obstetric Labor, Premature; Placenta; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome; Pregnancy Trimester, Second
PubMed: 18313635
DOI: 10.1016/j.ajog.2007.11.068 -
Placenta Oct 2023Detecting and quantifying surface densities of placental villi and their vasculature adds important information on the development of the placenta under different...
Detecting and quantifying surface densities of placental villi and their vasculature adds important information on the development of the placenta under different exposures and pathological conditions. Today, a larger number of samples and tissue areas can be examined using automated Artificial Intelligence-based approaches. Although each image series calls for a particular approach, sharing the methods will help in facilitating reproducibility and comparability. Here we show the protocol of a software-based quantification of vessels (number and area) in villous tissues of human placentas, based on scanned images of full-size placental sections.
Topics: Humans; Pregnancy; Female; Placenta; Artificial Intelligence; Reproducibility of Results; Chorionic Villi; Neovascularization, Pathologic
PubMed: 37688891
DOI: 10.1016/j.placenta.2023.09.002 -
Journal of Developmental Origins of... Apr 2021Observing fetal development in utero is vital to further the understanding of later-life diseases. Magnetic resonance imaging (MRI) offers a tool for obtaining a wealth... (Review)
Review
Observing fetal development in utero is vital to further the understanding of later-life diseases. Magnetic resonance imaging (MRI) offers a tool for obtaining a wealth of information about fetal growth, development, and programming not previously available using other methods. This review provides an overview of MRI techniques used to investigate the metabolic and cardiovascular consequences of the developmental origins of health and disease (DOHaD) hypothesis. These methods add to the understanding of the developing fetus by examining fetal growth and organ development, adipose tissue and body composition, fetal oximetry, placental microstructure, diffusion, perfusion, flow, and metabolism. MRI assessment of fetal growth, organ development, metabolism, and the amount of fetal adipose tissue could give early indicators of abnormal fetal development. Noninvasive fetal oximetry can accurately measure placental and fetal oxygenation, which improves current knowledge on placental function. Additionally, measuring deficiencies in the placenta's transport of nutrients and oxygen is critical for optimizing treatment. Overall, the detailed structural and functional information provided by MRI is valuable in guiding future investigations of DOHaD.
Topics: Cardiovascular System; Female; Fetal Development; Fetal Growth Retardation; Fetus; Humans; Magnetic Resonance Imaging; Placenta; Placenta Diseases; Placental Circulation; Pregnancy
PubMed: 33308364
DOI: 10.1017/S2040174420001154 -
Placental bed disorders in preterm labor, preterm PROM, spontaneous abortion and abruptio placentae.Best Practice & Research. Clinical... Jun 2011Failure of physiologic transformation of the spiral arteries has been studied using placental bed biopsies in several obstetrical syndromes. Contrary to what was... (Review)
Review
Failure of physiologic transformation of the spiral arteries has been studied using placental bed biopsies in several obstetrical syndromes. Contrary to what was originally believed, this lesion is not restricted to preeclampsia and/or intrauterine growth restriction. A review of published evidence indicates that failure of physiologic transformation can be observed in women with spontaneous second trimester abortions, preterm labor with intact membranes, preterm prelabor rupture of membranes and abruptio placentae. Therefore, disorders of deep placentation are present in a wide range of complications of pregnancy, emphasizing the importance of understanding the physiology and pathology of transformation of the spiral arteries. We propose that changes in the population and function of immunocytes at the maternal-fetal interface can be part of the mechanism of disease of obstetrical disorders, and this requires further investigation.
Topics: Abortion, Spontaneous; Abruptio Placentae; Female; Fetal Membranes, Premature Rupture; Humans; Obstetric Labor, Premature; Placenta; Placenta Diseases; Pregnancy
PubMed: 21388889
DOI: 10.1016/j.bpobgyn.2011.02.006 -
Ecotoxicology and Environmental Safety Sep 2021Nano-copper (nano-Cu) is widely used in the pharmaceutical field as well as a feed additive for animals owing to its unique physicochemical characteristics and...
Nano-copper (nano-Cu) is widely used in the pharmaceutical field as well as a feed additive for animals owing to its unique physicochemical characteristics and bioactivities. In our previous study, nano-Cu was found to hamper fetal development; however, the toxicity of nano-Cu and its effects in placental function have not been elucidated. Therefore, we investigated the toxic effects of nano-Cu using rat placenta. Pregnant Sprague-Dawley rats were orally exposed to different copper sources from the third day of gestation (GD 3) to GD 18. We found that nano-Cu (180 mg/kg) and CuCl.2 HO increased the accumulation of copper. Besides, nano-Cu and CuCl.2 HO disrupted the placental morphology and induced oxidative stress. Micro-copper (micro-Cu) caused similar toxicity in the placenta, but its effects were weaker than that of nano-Cu and CuCl.2 HO. In addition, exposure to nano-Cu (180 mg/kg) and CuCl.2 HO induced inflammation in the rat placenta. Furthermore, nano-Cu, micro-Cu, and CuCl.2 HO upregulated the expression of the autophagy-related proteins, Beclin-1 and LC3 II/ LC3 I, and downregulated that of p62. Moreover, nano-Cu, micro-Cu, and CuCl.2 HO downregulated the protein expression of PI3K, p-AKT/AKT, and p-mTOR/mTOR in rat placentas, whereas the protein expression of p-AMPK/AMPK was upregulated. Taken together, our data indicated that prenatal exposure to nano-Cu induced autophagy via the PI3K/AKT/mTOR and AMPK/mTOR pathways, which associated with oxidative stress and inflammation in rat placenta.
Topics: AMP-Activated Protein Kinases; Animals; Autophagy; Copper; Dietary Exposure; Female; Inflammation; Oxidative Stress; Phosphatidylinositol 3-Kinases; Placenta; Pregnancy; Rats; Rats, Sprague-Dawley; Signal Transduction; TOR Serine-Threonine Kinases
PubMed: 34051663
DOI: 10.1016/j.ecoenv.2021.112364 -
Food and Chemical Toxicology : An... Dec 2016Preeclampsia (PE) is a pregnancy disorder characterized by high blood pressure and proteinuria that can cause adverse health effects in both mother and fetus. There is... (Comparative Study)
Comparative Study
miRNAs as common regulators of the transforming growth factor (TGF)-β pathway in the preeclamptic placenta and cadmium-treated trophoblasts: Links between the environment, the epigenome and preeclampsia.
Preeclampsia (PE) is a pregnancy disorder characterized by high blood pressure and proteinuria that can cause adverse health effects in both mother and fetus. There is no current cure for PE other than delivery of the fetus/placenta. While the etiology is unknown, poor placentation due to aberrant signaling of growth and angiogenic factors has been postulated as a causal factor of PE. In addition, environmental contaminants, such as the metal cadmium (Cd), have been linked to placental toxicity and increased risk of developing PE. Here, we use a translational study design to investigate genomic and epigenomic alterations in both placentas and placental trophoblasts, focused on the angiogenesis-associated transforming growth factor-beta (TGF-β) pathway. Genes within the TGF-β pathway displayed increased expression in both the preeclamptic placenta and Cd-treated trophoblasts. In addition, miRNAs that target the TGF-β pathway were also significantly altered within the preeclamptic placenta and Cd-treated trophoblasts. Integrative analysis resulted in the identification of a subset of Cd-responsive miRNAs, including miR-26a and miR-155, common to preeclamptic placentas and Cd-treated trophoblasts. These miRNAs have previously been linked to PE and are predicted to regulate members of the TGF-β pathway. Results from this study provide future targets for PE treatment.
Topics: Cadmium; Case-Control Studies; Environment; Epigenomics; Female; Humans; MicroRNAs; Placenta; Pre-Eclampsia; Pregnancy; RNA, Messenger; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Transforming Growth Factor beta; Trophoblasts
PubMed: 27375191
DOI: 10.1016/j.fct.2016.06.023