17. Formation and Role of Placenta
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3 Embryology and Development
BIOL 6505 − INTRODUCTION TO FETAL MEDICINE 3. EMBRYOLOGY AND DEVELOPMENT Arlet G. Kurkchubasche, M.D. INTRODUCTION Embryology – the field of study that pertains to the developing organism/human Basic embryology –usually taught in the chronologic sequence of events. These events are the basis for understanding the congenital anomalies that we encounter in the fetus, and help explain the relationships to other organ system concerns. Below is a synopsis of some of the critical steps in embryogenesis from the anatomic rather than molecular basis. These concepts will be more intuitive and evident in conjunction with diagrams and animated sequences. This text is a synopsis of material provided in Langman’s Medical Embryology, 9th ed. First week – ovulation to fertilization to implantation Fertilization restores 1) the diploid number of chromosomes, 2) determines the chromosomal sex and 3) initiates cleavage. Cleavage of the fertilized ovum results in mitotic divisions generating blastomeres that form a 16-cell morula. The dense morula develops a central cavity and now forms the blastocyst, which restructures into 2 components. The inner cell mass forms the embryoblast and outer cell mass the trophoblast. Consequences for fetal management: Variances in cleavage, i.e. splitting of the zygote at various stages/locations - leads to monozygotic twinning with various relationships of the fetal membranes. Cleavage at later weeks will lead to conjoined twinning. Second week: the week of twos – marked by bilaminar germ disc formation. Commences with blastocyst partially embedded in endometrial stroma Trophoblast forms – 1) cytotrophoblast – mitotic cells that coalesce to form 2) syncytiotrophoblast – erodes into maternal tissues, forms lacunae which are critical to development of the uteroplacental circulation. -
Fetal Membrane Architecture, Aging and Inflammation in Pregnancy And
Placenta 79 (2019) 40–45 Contents lists available at ScienceDirect Placenta journal homepage: www.elsevier.com/locate/placenta Fetal membrane architecture, aging and inflammation in pregnancy and parturition T ∗ ∗∗ Ramkumar Menona, , Lauren S. Richardsona, Martha Lappasb,c, a Division of Maternal-Fetal Medicine & Perinatal Research, Department of Obstetrics & Gynecology, The University of Texas Medical Branch at Galveston, Galveston, TX, USA b Obstetrics, Nutrition and Endocrinology Group, Department of Obstetrics and Gynaecology, University of Melbourne, Mercy Hospital for Women, Heidelberg, Victoria, Australia c Department of Obstetrics and Gynaecology, University of Melbourne, Mercy Hospital for Women, Heidelberg, Victoria, Australia ARTICLE INFO ABSTRACT Keywords: Preterm birth is the single major cause of infant mortality. Short and long term outcomes for infants are often Fetal membranes worse in cases of preterm premature rupture of the fetal membranes (pPROM). Thus, increased knowledge of the Structure structure characteristics of fetal membranes as well as the mechanisms of membrane rupture are essential if we Senescence are to develop effective treatment strategies to prevent pPROM. In this review, we focus on the role of in- Inflammation flammation and senescence in fetal membrane biology. 1. Introduction 2. Fetal membrane growth and microfractures Human fetal membranes (placental membranes or amniochorionic Amnion and chorion takes distinct growth trajectory upon embry- membranes) is the innermost tissue layer that forms the intrauterine ogenesis [9]. The development of amnion and chorion begins with cavity [1,2]. Fetal membranes are comprised of amnion (innermost embryogenesis although they do not participate in the formation of the layer of the intraamniotic cavity) and chorion (fetal tissue connected to embryo or fetus [10–12]. -
CCM2 and CCM3 Proteins Contribute to Vasculogenesis and Angiogenesis in Human Placenta
Histol Histopathol (2009) 24: 1287-1294 Histology and http://www.hh.um.es Histopathology Cellular and Molecular Biology CCM2 and CCM3 proteins contribute to vasculogenesis and angiogenesis in human placenta Gamze Tanriover1, Yasemin Seval1, Leyla Sati1, Murat Gunel2 and Necdet Demir1 1Department of Histology and Embryology, Akdeniz University, School of Medicine, Antalya, Turkey and 2 Department of Neurosurgery, Yale University, School of Medicine, New Haven, CT, USA Summary. Placenta as an ideal model to study Introduction angiogenic mechanisms have been established in previous studies. There are two processes, The placenta is a multifaceted organ that plays a vasculogenesis and angiogenesis, involved in blood critical role in maintaining and protecting the developing vessel formation during placental development. fetus. Normal development and function of the placenta Therefore, blood vessel formation is a crucial issue that requires extensive vasculogenesis and subsequent might cause vascular malformations. One of the vascular angiogenesis, in both maternal and fetal tissues. malformations is cerebral cavernous malformation Vasculogenesis is the formation of the primitive vascular (CCM) in the central nervous system, consisting of network de novo from progenitor cells, and angiogenesis endothelium-lined vascular channels without intervening is identified as the extension of blood vessels from normal brain parenchyma. Three CCM loci have been preexisting vascular structures (Demir et al., 1989, 2006; mapped as Ccm1, Ccm2, Ccm3 genes in CCM. In order Geva et al., 2002; Charnock-Jones et al., 2004). Many to investigate whether CCM proteins participate in blood factors, such as vascular endothelial growth factor vessel formation, we report here the expression patterns (VEGF), angiopoietins (Angpt-1 and -2) and their of CCM2 and CCM3 in developing and term human receptors are involved in the molecular regulation of placenta by means of immunohistochemistry and these diverse developmental steps. -
Infections at the Maternal–Fetal Interface: an Overview of Pathogenesis and Defence
REVIEWS Infections at the maternal–fetal interface: an overview of pathogenesis and defence Christina J. Megli 1 ✉ and Carolyn B. Coyne 2 ✉ Abstract | Infections are a major threat to human reproductive health, and infections in pregnancy can cause prematurity or stillbirth, or can be vertically transmitted to the fetus leading to congenital infection and severe disease. The acronym ‘TORCH’ (Toxoplasma gondii, other, rubella virus, cytomegalovirus, herpes simplex virus) refers to pathogens directly associated with the development of congenital disease and includes diverse bacteria, viruses and parasites. The placenta restricts vertical transmission during pregnancy and has evolved robust mechanisms of microbial defence. However, microorganisms that cause congenital disease have likely evolved diverse mechanisms to bypass these defences. In this Review, we discuss how TORCH pathogens access the intra- amniotic space and overcome the placental defences that protect against microbial vertical transmission. Infections during pregnancy can be associated with pathogen mediated, placenta mediated and/or can be devastating consequences to the pregnant mother and through inflammation induced previable delivery. developing fetus. Vertical transmission, defined as There are also outcomes of congenital infections that infection of the fetus from the maternal host, is a major do not manifest until after delivery. These can include cause of morbidity and mortality in pregnancy. In some hearing loss, developmental delays and/or blindness as cases, bacterial, viral and parasitic infections induce detailed below. dire outcomes in the fetus. The sequelae of infections Inflammation initiated by an infection of the mater in pregnancy include teratogenic effects, which cause nal host is also a known cause of preterm labour and can congenital anomalies; growth restriction, stillbirth, mis result in previable delivery or sequelae of prematurity10 carriage and neonatal death; prematurity; and maternal with lifelong consequences to the neonate. -
Defective Decidualization During and After Severe Preeclampsia Reveals a Possible Maternal Contribution to the Etiology
Defective decidualization during and after severe preeclampsia reveals a possible maternal contribution to the etiology Tamara Garrido-Gomeza,b,c,d, Francisco Dominguezb, Alicia Quiñonerob, Patricia Diaz-Gimenob, Mirhan Kapidzicc,d, Matthew Gormleyc,d, Katherine Onac,d, Pablo Padilla-Isertee, Michael McMasterf, Olga Genbacevc,d, Alfredo Peralese,g, Susan J. Fisherc,d,h,i,1,2, and Carlos Simóna,b,g,j,1,2 aFundación Igenomix, 46980 Valencia, Spain; bInstituto Universitario IVI, Instituto de Investigación Sanitaria Hospital Clinico de Valencia INCLIVA, 46010 Valencia, Spain; cCenter for Reproductive Sciences, University of California, San Francisco, CA 94143; dDepartment of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, CA 94143; eDepartment of Obstetrics and Gynecology, Hospital Universitario La Fe, 46026 Valencia, Spain; fDepartment of Cell and Tissue Biology, University of California, San Francisco, CA 94143; gDepartment of Obstetrics and Gynecology, School of Medicine, Valencia University, 46010 Valencia, Spain; hThe Eli & Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA 94143; iDepartment of Anatomy, University of California, San Francisco, CA 94143; and jDepartment of Obstetrics and Gynecology, School of Medicine, Stanford University, Palo Alto, CA 94305 Edited by R. Michael Roberts, University of Missouri-Columbia, Columbia, MO, and approved August 11, 2017 (received for review April 20, 2017) In preeclampsia (PE), cytotrophoblast (CTB) invasion of the uterus in studying the CTB subpopulation that invades the uterine wall in and spiral arteries is often shallow. Thus, the placenta’s role has the context of this syndrome. Targeted analyses of particular mo- been a focus. In this study, we tested the hypothesis that decidual lecular families, such as the vascular-type adhesion molecules that defects are an important determinant of the placental phenotype. -
Human Pluripotent Stem Cells As a Model of Trophoblast Differentiation in Both Normal Development and Disease
Human pluripotent stem cells as a model of trophoblast differentiation in both normal development and disease Mariko Horiia,b,1, Yingchun Lia,b,1, Anna K. Wakelanda,b,1, Donald P. Pizzoa, Katharine K. Nelsona,b, Karen Sabatinib,c, Louise Chang Laurentb,c, Ying Liud,e,f, and Mana M. Parasta,b,2 aDepartment of Pathology, University of California, San Diego, La Jolla, CA 92093; bSanford Consortium for Regenerative Medicine, University of California, San Diego, La Jolla, CA 92093; cDepartment of Reproductive Medicine, University of California, San Diego, La Jolla, CA 92093; dDepartment of Neurosurgery, Center for Stem Cell and Regenerative Medicine, University of Texas Health Sciences Center, Houston, TX 77030; eThe Senator Lloyd and B. A. Bentsen Center for Stroke Research, University of Texas Health Sciences Center, Houston, TX 77030; and fThe Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas Health Sciences Center, Houston, TX 77030 Edited by R. Michael Roberts, University of Missouri–Columbia, Columbia, MO, and approved May 25, 2016 (received for review March 24, 2016) Trophoblast is the primary epithelial cell type in the placenta, a Elf5 (Ets domain transcription factor) and Eomes (Eomeso- transient organ required for proper fetal growth and develop- dermin), also have been shown to be required for maintenance of ment. Different trophoblast subtypes are responsible for gas/nutrient the TSC fate in the mouse (8, 9). exchange (syncytiotrophoblasts, STBs) and invasion and maternal Significantly less is known about TE specification and the TSC vascular remodeling (extravillous trophoblasts, EVTs). Studies of niche in the human embryo (10, 11). -
Decidua Produces a Protein That Inhibits Choriogonadotrophin Release from Human Trophoblasts
Decidua produces a protein that inhibits choriogonadotrophin release from human trophoblasts. S G Ren, G D Braunstein J Clin Invest. 1991;87(1):326-330. https://doi.org/10.1172/JCI114990. Research Article To test the hypothesis that uterine decidua may modulate trophoblast function, trophoblasts and decidual cells were isolated from term placentas by enzymatic digestion and Percoll gradient centrifugation. Placental trophoblasts were cocultured with decidual cells and trophoblasts or JEG-3 choriocarcinoma cells were incubated with medium conditioned by decidual cells (DCM) for 72-96 h. In cocultures decidual cells inhibited choriogonadotropin (hCG) release from trophoblasts by 75% in comparison with controls (P less than 0.001). The DCM contained a factor that markedly inhibited hCG release from trophoblasts and JEG cells in vitro compared with controls. The inhibitory effect of the factor on hCG release was dose dependent, and could be eliminated by boiling the DCM for 30 min or proteolytic enzyme treatment. Ultrafiltration and Sephadex G-50 fractionation of the DCM indicated that the apparent molecular mass was 7,000-10,000 D. DCM also inhibited the stimulatory effect of exogenous cAMP on hCG secretion by JEG-3 cells, suggesting that DCM may interfere with activation of the cAMP-dependent protein kinases or transcription of hCG genes. These results suggest that the release of trophoblast hCG is under local paracrine control, regulated in part by a protein released by decidual cells. Find the latest version: https://jci.me/114990/pdf Decidua Produces a Protein that Inhibits Choriogonadotrophin Release from Human Trophoblasts Song-Guang Ren and Glenn D. -
Characteristic Changes in Decidual Gene Expression Signature in Spontaneous Term Parturition
Journal of Pathology and Translational Medicine 2017; 51: 264-283 ▒ ORIGINAL ARTICLE ▒ https://doi.org/10.4132/jptm.2016.12.20 Characteristic Changes in Decidual Gene Expression Signature in Spontaneous Term Parturition Haidy El-Azzamy1,* · Andrea Balogh1,2,* Background: The decidua has been implicated in the “terminal pathway” of human term parturi- Roberto Romero1,3,4,5 · Yi Xu1 tion, which is characterized by the activation of pro-inflammatory pathways in gestational tissues. Christopher LaJeunesse1 · Olesya Plazyo1 However, the transcriptomic changes in the decidua leading to terminal pathway activation have Zhonghui Xu1 · Theodore G. Price1 not been systematically explored. This study aimed to compare the decidual expression of devel- Zhong Dong1 · Adi L. Tarca1,6 opmental signaling and inflammation-related genes before and after spontaneous term labor in Zoltan Papp7 · Sonia S. Hassan1,6 order to reveal their involvement in this process. Methods: Chorioamniotic membranes were 1,6 Tinnakorn Chaiworapongsa obtained from normal pregnant women who delivered at term with spontaneous labor (TIL, n = 14) 1,8,9 Chong Jai Kim or without labor (TNL, n = 15). Decidual cells were isolated from snap-frozen chorioamniotic mem- Nardhy Gomez-Lopez1,6 branes with laser microdissection. The expression of 46 genes involved in decidual development, Nandor Gabor Than1,6,7,10,11 sex steroid and prostaglandin signaling, as well as pro- and anti-inflammatory pathways, was ana- lyzed using high-throughput quantitative real-time polymerase chain reaction (qRT-PCR). Chorio- 1Perinatology Research Branch, NICHD/NIH/DHHS, amniotic membrane sections were immunostained and then semi-quantified for five proteins, and Bethesda, MD, and Detroit, MI, USA; 2Department of Immunology, Eotvos Lorand University, Budapest, immunoassays for three chemokines were performed on maternal plasma samples. -
The Placenta
The placenta Learning module Developed by Carolyn Hammer Edited by Fabien Giroux Diagrams By Dr Julien Yockell Lelievre where indicated The placenta – Learning module Table of content 1) Introduction……………………………………………………………………….3 2) Anatomy and Physiology………………………………………………………..6 3) Roles and Functions……………………………………………………………17 4) Development and formation…………………………………..…………….…27 5) What happens after birth……………………………………………….……...34 6) What happens when things go wrong.……………………………………….36 7) Interesting facts about pregnancy………………….…………………………46 2 The placenta – Learning module Introduction 3 The placenta – Learning module What is the placenta? •The placenta is a “vascular (supplied with blood vessels) organ in most mammals that unites the fetus to the uterus of the mother. It mediates the metabolic exchanges of the developing individual through an intimate association of embryonic tissues and of certain uterine tissues, serving the functions of nutrition, respiration, and excretion.” (Online Britannica encyclopaedia) •As the fetus is in full development, it requires a certain amount of gases and nutrients to help support its growth. Because the fetus is unable to do so on its own, the placenta provides these gases and nutrients throughout pregnancy. http://health.allrefer.com/health/plac enta-abruptio-placenta.html 4 The placenta – Learning module What are the main roles of the placenta? •The placenta provides the connection between fetus and mother in order to help carry out many different functions that the growing baby is incapable to do so alone. During pregnancy, the placenta has 6 main roles to maintain good health and a good environment for the growing child: •Respiration •Nutrition •Excretion •Protection •Endocrine •Immunity 5 The placenta – Learning module Anatomy and physiology 6 The placenta – Learning module Structure •A placenta is an organ of round or oval shape that is relatively flat. -
Increased Apoptosis in Chorionic Trophoblasts of Human Fetal Membranes with Labor at Term*
International Journal of Clinical Medicine, 2012, 3, 136-142 http://dx.doi.org/10.4236/ijcm.2012.32027 Published Online March 2012 (http://www.SciRP.org/journal/ijcm) Increased Apoptosis in Chorionic Trophoblasts of Human * Fetal Membranes with Labor at Term Hassan M. Harirah1#, Mostafa A. Borahay1, Wahidu Zaman1, Mahmoud S. Ahmed1, Ibrahim G. Hager2, Gary D. V. Hankins1 1The Department of Obstetrics & Gynecology, The University of Texas Medical Branch, Galveston, USA; 2The Department of Ob- stetrics & Gynecology, Zagazig University, Zagazig, Egypt. Email: #[email protected] Received December 7th, 2011; revised January 17th, 2012; accepted February 8th, 2012 ABSTRACT Objective: To determine the association of apoptosis in the layers of human fetal membranes distal to rupture site with labor at term. Study Design: Fetal membranes were collected from elective cesarean sections (n = 8) and spontaneous vaginal deliveries (n = 8) at term. The extent of apoptosis within fetal membrane layers was determined using terminal deoxynucleotidyl transferase deoxy-UTP-nick end labeling (TUNEL) assay and western blots for pro-apoptotic active caspase-3 and anti-apoptotic Bcl-2. Results: Apoptotic index in chorionic trophoblasts of membranes distal to rupture site obtained after vaginal delivery was 3-fold higher than those obtained from elective cesarean (11.57% ± 4.98% and 4.05% ± 2.4% respectively; p = 0.012). The choriodecidua layers after vaginal deliveries had higher expression of the pro-apoptotic active caspase-3 and less expression of the anti-apoptotic Bcl-2 than those obtained from elective cesar- ean sections. Conclusions: Labor at term is associated with increased apoptosis in chorionic trophoblast cells of human fetal membranes distal to rupture site. -
Mammalogy Lecture 12
Mammalogy Lecture 11 - Reproduction I: General Patterns I. Obviously, reproduction is a very important aspect of biology and whole courses are dedicated to it. It’s easy to understand why reproductive traits would be subject to strong selection because of their direct effects on fitness. II. As we might expect, there are three basic types of mammalian reproduction. These correspond to the three major groups of mammals. Differences among these types reflect the degree of intimacy of fetal-maternal contact. A. Monotreme Type - Retain the primitive amniote pattern, but add a period of lactation. - Egg is very large at ovulation, about 3 mm. It moves down the oviduct where it is fertilized, then it’s coated with albumin, then a shell is laid down by a shell gland, and the shell is mineralized (with CaCO3). - Embryo spends 2-3 weeks in the uterus, then it’s laid. It’s large, 15 mm, when it’s laid. - Embryo growth is supported entirely by the yolk that’s enclosed in the egg. B. Metatherian type: - In some superficial ways it’s similar to monotremes, in that metatherians retain a shell membrane around the fertilized egg; a shell gland is present in Müllerian ducts. - However the shell is never mineralized and young are born live after only ca. 12 days, as we’ve seen, they are very altricial (poorly developed). - Initial intrauterine growth is supported by maternally by a placenta. - Metatherian placenta is the choriovitelline type - yolk-sac placenta (Eutherian placenta is called chorioallantoic placenta) C. Placenta Formation - Let’s look at formation of the placenta in Meta- & Eutherians. -
Adhesive and Degradative Properties of Human Placental Cytotrophoblast Cells in Vitro Susan J
Adhesive and Degradative Properties of Human Placental Cytotrophoblast Cells In Vitro Susan J. Fisher, Tian-yi Cui, Li Zhang, Lynn Hartman, Kim Grahl, Zhang Guo-Yang, John Tarpey, and Caroline H. Damsky Departments of Stomatology, Anatomy, and Pharmaceutical Chemistry, University of California at San Francisco, San Francisco, California 94143 Abstract. Human fetal development depends on the ponents into the medium. No similar degradative ac- embryo rapidly gaining access to the maternal circula- tivity was observed when second or third trimester tion. The trophoblast cells that form the fetal portion cytotrophoblast cells, first trimester human placental of the human placenta have solved this problem by fibroblasts, or the human choriocarcinoma cell lines transiently exhibiting certain tumor-like properties. BeWo and JAR were cultured on radiolabeled matrices. Thus, during early pregnancy fetal cytotrophoblast To begin to understand the biochemical basis of this cells invade the uterus and its arterial network. This degradative behavior, the substrate gel technique was process peaks during the twelfth week of pregnancy used to analyze the cell-associated and secreted pro- and declines rapidly thereafter, suggesting that the teinase activities expressed by early, mid, and late highly specialized, invasive behavior of the cytotropho- gestation cytotrophoblasts. Several gelatin-degrading blast cells is closely regulated. Since little is known proteinases were uniquely expressed by early gesta- about the actual mechanisms involved, we developed tion, invasive cytotrophoblasts, and all these activities an isolation procedure for cytotrophoblasts from could be abolished by inhibitors of metalloproteinases. placentas of different gestational ages to study their By early second trimester, the time when cytotropho- adhesive and invasive properties in vitro.