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Genes To Cells : Devoted To Molecular &... Oct 2015It is well accepted that numerous RNAs derived from endogenous retroviruses (ERVs) are expressed in mammalian reproductive structures, particularly in the uterus,... (Review)
Review
It is well accepted that numerous RNAs derived from endogenous retroviruses (ERVs) are expressed in mammalian reproductive structures, particularly in the uterus, trophoblast, and placenta. Syncytin 1 and syncytin 2 in humans and syncytin A and syncytin B in mice are membrane proteins originating from Env genes of ERVs. These ERVs are involved in the fusion of trophoblast cells, resulting in multinucleated syncytiotrophoblast formation. Evidence accumulated indicates that syncytin-like fusogenic proteins are expressed in the placenta of rabbits, dogs/cats, ruminant ungulates, tenrecs, and opossums. The syncytin genes so far characterized are known to be endogenized to the host genome only within the past 12-80 million years, more recently than the appearance of mammalian placentas, estimated to be 160-180 million years ago. We speculate that ERVs including syncytin-like gene variants integrated into mammalian genomes in a locus-specific manner have replaced the genes previously responsible for cell fusion. We therefore propose the 'baton pass' hypothesis, in which multiple successive ERV variants 'take over' cell-fusion roles, resulting in increased trophoblast cell fusion, morphological variations in placental structures, and enhanced reproductive success in placental mammals.
Topics: Animals; Cell Fusion; Endogenous Retroviruses; Evolution, Molecular; Female; Gene Products, env; Genes, Viral; Humans; Mammals; Placenta; Placentation; Pregnancy; Pregnancy Proteins
PubMed: 26442811
DOI: 10.1111/gtc.12278 -
IEEE Transactions on Visualization and... Jun 2017The human placenta is essential for the supply of the fetus. To monitor the fetal development, imaging data is acquired using (US). Although it is currently the...
The human placenta is essential for the supply of the fetus. To monitor the fetal development, imaging data is acquired using (US). Although it is currently the gold-standard in fetal imaging, it might not capture certain abnormalities of the placenta. (MRI) is a safe alternative for the in utero examination while acquiring the fetus data in higher detail. Nevertheless, there is currently no established procedure for assessing the condition of the placenta and consequently the fetal health. Due to maternal respiration and inherent movements of the fetus during examination, a quantitative assessment of the placenta requires fetal motion compensation, precise placenta segmentation and a standardized visualization, which are challenging tasks. Utilizing advanced motion compensation and automatic segmentation methods to extract the highly versatile shape of the placenta, we introduce a novel visualization technique that presents the fetal and maternal side of the placenta in a standardized way. Our approach enables physicians to explore the placenta even in utero. This establishes the basis for a comparative assessment of multiple placentas to analyze possible pathologic arrangements and to support the research and understanding of this vital organ. Additionally, we propose a three-dimensional structure-aware surface slicing technique in order to explore relevant regions inside the placenta. Finally, to survey the applicability of our approach, we consulted clinical experts in prenatal diagnostics and imaging. We received mainly positive feedback, especially the applicability of our technique for research purposes was appreciated.
Topics: Female; Fetus; Humans; Image Interpretation, Computer-Assisted; Magnetic Resonance Imaging; Placenta; Pregnancy; Prenatal Diagnosis
PubMed: 28252405
DOI: 10.1109/TVCG.2017.2674938 -
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 -
The Journal of Reproduction and... Jun 2019Preeclampsia is a systemic disease caused by abnormal placentation that affects both mother and fetus. It was reported that Laeverin (LVRN, also known as Aminopeptidase...
Preeclampsia is a systemic disease caused by abnormal placentation that affects both mother and fetus. It was reported that Laeverin (LVRN, also known as Aminopeptidase Q) was up-regulated in the placenta of preeclamptic patients. However, physiological and pathological functions of LVRN remained to be unknown. Here we characterized Lvrn function during placentation in mice. RT-PCR showed that Lvrn is expressed in both fetus and placenta during embryogenesis, and several adult tissues. When we overexpressed Lvrn in a placenta-specific manner using lentiviral vectors, we did not see any defects in both placentae and fetuses. The mice carrying Lvrn overexpressing placentas did not show any preeclampsia-like symptoms such as maternal high blood pressure and fetal growth restriction. We next ablated Lvrn by CRISPR/Cas9-mediated genome editing to see physiological function. In Lvrn ablated mice, maternal blood pressure during pregnancy was not affected, and both placentas and fetuses grew normally. Collectively, these results suggest that, LVRN is irrelevant to preeclampsia and dispensable for normal placentation and embryonic development in mice.
Topics: Animals; Blood Pressure; CRISPR-Cas Systems; Female; Fetal Growth Retardation; Fetus; Gene Expression Profiling; Gene Expression Regulation, Developmental; Lentivirus; Metalloproteases; Mice; Mice, Knockout; Placenta; Placentation; Pre-Eclampsia; Pregnancy; Pregnancy, Animal; Trophoblasts
PubMed: 30745494
DOI: 10.1262/jrd.2018-157 -
Scientific Reports Mar 2021Previously, we identified increased maternal circulating DAAM2 mRNA in pregnancies complicated by preterm fetal growth restriction (FGR). Here, we assessed whether... (Clinical Trial)
Clinical Trial
Previously, we identified increased maternal circulating DAAM2 mRNA in pregnancies complicated by preterm fetal growth restriction (FGR). Here, we assessed whether circulating DAAM2 mRNA could detect FGR, and whether the DAAM2 gene, known to play roles in the Wnt signalling pathway is expressed in human placenta and associated with dysfunction and FGR. We performed linear regression analysis to calculate area under the ROC curve (AUC) for DAAM2 mRNA expression in the maternal circulation of pregnancies complicated by preterm FGR. DAAM2 mRNA expression was assessed across gestation by qPCR. DAAM2 protein and mRNA expression was assessed in preterm FGR placenta using western blot and qPCR. DAAM2 expression was assessed in term cytotrophoblasts and placental explant tissue cultured under hypoxic and normoxic conditions by qPCR. Small interfering RNAs were used to silence DAAM2 in term primary cytotrophoblasts. Expression of growth, apoptosis and oxidative stress genes were assessed by qPCR. Circulating DAAM2 mRNA was elevated in pregnancies complicated by preterm FGR [p < 0.0001, AUC = 0.83 (0.78-0.89)]. Placental DAAM2 mRNA was detectable across gestation, with highest expression at term. DAAM2 protein was increased in preterm FGR placentas but demonstrated no change in mRNA expression. DAAM2 mRNA expression was increased in cytotrophoblasts and placental explants under hypoxia. Silencing DAAM2 under hypoxia decreased expression of pro-survival gene, BCL2 and oxidative stress marker, NOX4, whilst increasing expression of antioxidant enzyme, HMOX-1. The increased DAAM2 associated with FGR and hypoxia implicates a potential role in placental dysfunction. Decreasing DAAM2 may have cytoprotective effects, but further research is required to elucidate its role in healthy and dysfunctional placentas.
Topics: Adult; Female; Fetal Growth Retardation; Gene Expression Regulation; Humans; Hypoxia; Microfilament Proteins; Placenta; Pregnancy; RNA, Messenger; rho GTP-Binding Proteins
PubMed: 33692394
DOI: 10.1038/s41598-021-84785-7 -
International Journal of Molecular... Feb 2021Steroid hormones play a crucial role in supporting a successful pregnancy and ensuring proper fetal development. The placenta is one of the principal tissues in steroid...
Steroid hormones play a crucial role in supporting a successful pregnancy and ensuring proper fetal development. The placenta is one of the principal tissues in steroid production and metabolism, expressing a vast range of steroidogenic enzymes. Nevertheless, a comprehensive characterization of steroidogenic pathways in the human placenta and potential developmental changes occurring during gestation are poorly understood. Furthermore, the specific contribution of trophoblast cells in steroid release is largely unknown. Thus, this study aimed to (i) identify gestational age-dependent changes in the gene expression of key steroidogenic enzymes and (ii) explore the role of trophoblast cells in steroid biosynthesis and metabolism. Quantitative and Droplet Digital PCR analysis of 12 selected enzymes was carried out in the first trimester ( = 13) and term ( = 20) human placentas. Primary trophoblast cells ( = 5) isolated from human term placentas and choriocarcinoma-derived cell lines (BeWo, BeWo b30 clone, and JEG-3) were further screened for gene expression of enzymes involved in placental synthesis/metabolism of steroids. Finally, de novo steroid synthesis by primary human trophoblasts was evaluated, highlighting the functional activity of steroidogenic enzymes in these cells. Collectively, we provide insights into the expression patterns of steroidogenic enzymes as a function of gestational age and delineate the cellular origin of steroidogenesis in the human placenta.
Topics: Adult; Cells, Cultured; Choriocarcinoma; Female; Gene Expression Regulation; Gestational Age; Humans; Infant, Newborn; Placenta; Pregnancy; Pregnancy Trimester, First; Steroid Hydroxylases; Steroids; Trophoblasts
PubMed: 33567726
DOI: 10.3390/ijms22041704 -
International Journal of Molecular... Dec 2022As the mediator between the mother and fetus, the placenta allows the most appropriate environment and optimal fetal growth. The placenta of one sex sometimes has a...
As the mediator between the mother and fetus, the placenta allows the most appropriate environment and optimal fetal growth. The placenta of one sex sometimes has a greater ability over the other to respond to and protect against possible maternal insults. Here, we characterized sex differences in the placenta’s morphological features and antioxidant status following dexamethasone (Dx) exposure. Pregnant rats were exposed to Dx or saline. The placenta was histologically and stereologically analyzed. The activity of the antioxidant enzymes, lipid peroxides (TBARS), superoxide anion and nitric oxide (NO) was measured. The decrease in placental zone volumes was more pronounced (p < 0.05) in female placentas. The volume density of PCNA-immunopositive nuclei was reduced (p < 0.05) in both sexes. The reduced (p < 0.05) antioxidant enzyme activities, enhanced TBARS and NO concentration indicate that Dx exposure triggered oxidative stress in the placenta of both fetal sexes, albeit stronger in the placenta of female fetuses. In conclusion, maternal Dx treatment reduced the size and volume of placental zones, altered placental histomorphology, decreased cell proliferation and triggered oxidative stress; however, the placentas of female fetuses exerted more significant responses to the treatment effects. The reduced placental size most probably reduced the transport of nutrients and oxygen, thus resulting in the reduced weight of fetuses, similar in both sexes. The lesser ability of the male placenta to detect and react to maternal exposure to environmental challenges may lead to long-standing health effects.
Topics: Animals; Female; Male; Pregnancy; Rats; Antioxidants; Dexamethasone; Maternal Exposure; Oxidation-Reduction; Placenta; Thiobarbituric Acid Reactive Substances
PubMed: 36613982
DOI: 10.3390/ijms24010540 -
Molecular Biology and Evolution Oct 2021In mammals, the placenta mediates maternal-fetal nutrient and waste exchange and acts in an immunomodulatory way to facilitate maternal-fetal tolerance. The placenta is...
In mammals, the placenta mediates maternal-fetal nutrient and waste exchange and acts in an immunomodulatory way to facilitate maternal-fetal tolerance. The placenta is highly diverse across mammalian species, yet the molecular mechanisms that distinguish the placenta of human from other mammals are not fully understood. Using an interspecies transcriptomic comparison of human, macaque, and mouse late-gestation placentae, we identified hundreds of genes with lineage-specific expression-including dozens that are placentally enriched and potentially related to pregnancy. We further annotated the enhancers for different human tissues using epigenomic data and demonstrate that the placenta and chorion are unique in that their enhancers display the least conservation. We identified numerous lineage-specific human placental enhancers and found they highly overlap with specific families of endogenous retroviruses (ERVs), including MER21A, MER41A/B, and MER39B that were previously linked to immune response and placental function. Among these ERV families, we further demonstrate that MER41A/B insertions create dozens of lineage-specific serum response factor-binding loci in human, including one adjacent to FBN2, a placenta-specific gene with increased expression in humans that produces the peptide hormone placensin to stimulate glucose secretion and trophoblast invasion. Overall, our results demonstrate the prevalence of lineage-specific placental enhancers which are frequently associated with ERV insertions and likely facilitate the lineage-specific evolution of the mammalian placenta.
Topics: Animals; Endogenous Retroviruses; Female; Mice; Placenta; Pregnancy; Primates; Rodentia; Trophoblasts
PubMed: 34320657
DOI: 10.1093/molbev/msab223 -
Placenta Jun 2021Fatty acids are essential nutrients for the fetus and are supplied by the mother through the placenta. Desaturase and elongase enzymes play an important role in...
INTRODUCTION
Fatty acids are essential nutrients for the fetus and are supplied by the mother through the placenta. Desaturase and elongase enzymes play an important role in modulating the fatty acid composition of body tissues. We aimed to compare the fatty acid profile and the estimated desaturase and elongase activities in the placenta of appropriate (AGA) versus small-for-gestational-age (SGA), and to determine their relationship with the offspring size at birth.
METHODS
The placental fatty acid profile was analyzed by gas chromatography in 84 infants (45 AGA and 30 SGA) from a prenatal cohort study. The estimated desaturase and elongase activities were calculated from product-precursor fatty acid ratios. Results were associated with maternal (age, body mass index and weight gain during gestation) and neonatal (gestational age, sex, birth weight and birth length) parameters.
RESULTS
Differences in placental fatty acid composition between AGA and SGA infants rather than correlations thereof with neonatal parameters were observed. Placentas from SGA infants contained lower levels of omega-3 (ALA, EPA, DPA, and DHA) and high omega-6/omega-3 ratios (AA/DHA and LA/ALA), as well as low elongase (Elovl5) and high desaturase (D9Dn7 and D5Dn6) activity as compared to AGA infants (all p < 0.0001).
DISCUSSION
Placentas of AGA and SGA infants differed in fatty acids profile as well as in estimated desaturase and elongase activities. A striking feature of SGA placentas was the low availability of omega-3. Hence, omega-3 fatty acid status deserves further attention, as a potential target of prenatal interventions.
Topics: Adult; Birth Weight; Case-Control Studies; Cohort Studies; Fatty Acids; Female; Gestational Age; Humans; Infant, Newborn; Infant, Small for Gestational Age; Male; Placenta; Pregnancy; Term Birth; Weight Gain
PubMed: 33895685
DOI: 10.1016/j.placenta.2021.04.009 -
Acta Obstetricia Et Gynecologica... Sep 2017A validation of data regarding the placenta, cord and membranes in Medical Birth Registry of Norway (MBRN) is lacking. Here we investigate the inter- and intra-observer...
INTRODUCTION
A validation of data regarding the placenta, cord and membranes in Medical Birth Registry of Norway (MBRN) is lacking. Here we investigate the inter- and intra-observer agreement of observations regarding the placenta, cord and membranes to the MBRN in two institutions.
MATERIAL AND METHODS
We conducted a dual center validation study of data regarding placenta, cord and membranes. In the inter-observer study, 196 placentas in two institutions were examined by the attending midwife and a blinded colleague, whereas in the intra-observer study registrations by the attending midwife on 195 placentas were compared with her own registrations to the MBRN. In a separate sample consisting of 51 placental pathology reports, midwives' registrations to the MBRN were compared with the pathology report. For categorical and continuous variables, agreement was assessed by kappa value and paired sample t-test, respectively.
RESULTS
Inter-observer agreement between two midwives for cord insertion site and bi-placenta, cord knots and vessel anomalies were good (kappa values >0.79 and >0.96, respectively). The inter- and intra-observer study showed no significant differences regarding placental weight and cord length (p = 0.31 and 0.28, p = 0.71 and 0.39, respectively). The inter-observer agreement between the pathology reports and midwives' registrations was good for gross placental and cord variants (kappa 0.73-1.0), but there were significant differences in placental weight and cord length (p < 0.0001).
CONCLUSIONS
The results suggest that the validity of data regarding placenta and cord in the MBRN is sufficiently high to justify future large-scale epidemiologic research based on this database.
Topics: Delivery, Obstetric; Female; Humans; Management Information Systems; Midwifery; Norway; Placenta; Pregnancy; Registries; Reproducibility of Results; Umbilical Cord
PubMed: 28481411
DOI: 10.1111/aogs.13164