DOCSLIB.ORG

Perinatal Mesenchymal Stromal Cells and Their Possible Contribution to Fetal-Maternal Tolerance

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Perinatal Mesenchymal Stromal Cells and Their Possible Contribution to Fetal-Maternal Tolerance cells Review Perinatal Mesenchymal Stromal Cells and Their Possible Contribution to Fetal-Maternal Tolerance Marta Magatti 1, Francesca Romana Stefani 1 , Andrea Papait 1, Anna Cargnoni 1, Alice Masserdotti 2, Antonietta Rosa Silini 1 and Ornella Parolini 1,2,* 1 Centro di Ricerca E. Menni, Fondazione Poliambulanza Istituto Ospedaliero, 25124 Brescia, Italy; [email protected] (M.M.); [email protected] (F.R.S.); [email protected] (A.P.); [email protected] (A.C.); [email protected] (A.R.S.) 2 Istituto di Anatomia Umana e Biologia Cellulare, Università Cattolica del Sacro Cuore, 00168 Roma, Italy; [email protected] * Correspondence: [email protected]; Tel.: +39-0630154464 Received: 27 September 2019; Accepted: 3 November 2019; Published: 7 November 2019 Abstract: During pregnancy, a successful coexistence between the mother and the semi-allogenic fetus occurs which requires a dynamic immune system to guarantee an efficient immune protection against possible infections and tolerance toward fetal antigens. The mechanism of fetal-maternal tolerance is still an open question. There is growing in vitro and in vivo evidence that mesenchymal stromal cells (MSC) which are present in perinatal tissues have a prominent role in generating a functional microenvironment critical to a successful pregnancy. This review highlights the immunomodulatory properties of perinatal MSC and their impact on the major immune cell subsets present in the uterus during pregnancy, such as natural killer cells, antigen-presenting cells (macrophages and dendritic cells), and T cells. Here, we discuss the current understanding and the possible contribution of perinatal MSC in the establishment of fetal-maternal tolerance, providing a new perspective on the physiology of gestation. Keywords: mesenchymal stromal cells; placenta; fetal-maternal tolerance; immunomodulation; pregnancy 1. Immunology of Pregnancy In nature, pregnancy is a unique physiological phenomenon in which the mother coexists with the semi-allogeneic fetus that carries a combination of antigens half of which are paternal. For many years, Medawar’s paradox has provided the basis for the model that explains the cohabitation of mother and fetus [1]. Medawar proposed that the lack of fetal rejection by the mother might be explained by diverse mechanisms, which include: (a) the non-immunogenicity of the fetus due to antigenic immaturity, (b) the suppression of the mother’s immune system during pregnancy that in turn causes the mother’s immune system to “ignore” the fetus, (c) the uterus as an immunologically privileged site; and (d) the existence of an immunological barrier between mother and fetus, represented by the placenta [2]. Since the time of Medawar, the following has been demonstrated: (a) the fetus has immunogenic properties; (b) the maternal immune response is not suppressed during pregnancy; (c) the uterus does not represent an immune-privileged site and extrauterine pregnancies are also possible [3,4]; and (d) there are no physical barriers from immune cells in the placenta, and this is particularly true considering the human hemochorial placental arrangement [5], therefore, allowing bidirectional cell trafficking between the fetus and the mother [6]. Thus, placental tissue represents an active immunological site rather than a merely passive barrier from the mother. There is a great deal of evidence suggesting that a successful Cells 2019, 8, 1401; doi:10.3390/cells8111401 www.mdpi.com/journal/cells Cells 2019, 8, 1401 2 of 22 Cells 2018, 7, x FOR PEER REVIEW 2 of 23 pregnancyis a great requires deal of evidence a responsive suggesting and dynamic that a successful immune pregnancy system from requires both thea responsive mother and and the dynamic fetal and placentalimmune compartments system from both in order the mother to guarantee and the fetal efficient and placental immune protectioncompartments against in order possible to guarantee infections andefficient tolerance immune toward protection fetal antigens. against possible In line with infections the idea and of tolerance a plastic toward immune fetal remodeling, antigens. In distinctline immunologicalwith the idea of stages a plastic are immune identified remodeling, during pregnancy, distinct immunological as previously stages extensively are identified described during [7 ,8] (Figurepregnancy,1). At first,as previously a local proinflammatory extensively described reaction [7,8] accompanies (Figure 1). At the first, adhesion a local andproinflammatory invasion of the trophoblastreaction accompanies to maternal the tissues. adhesion Indeed, and invasion at the beginning of the trophoblast of pregnancy, to maternal the maternaltissues. Indeed, endometrium at the undergoesbeginning a processof pregnancy, called decidualization, the maternal endometrium characterized undergoes by proliferation a process and called differentiation decidualization, of stromal cells.characterized The stromal by cells proliferation release cytokines and differentiation and growth of stromal factors (mainlycells. The prolactin stromal cells and release insulin-like cytokines growth factorand binding growth protein-1)factors (mainly that modify prolactin the and extracellular insulin-like matrix growth and factor expose binding adhesion protein-1) molecules that inmodify order to the extracellular matrix and expose adhesion molecules in order to create a receptive create a receptive microenvironment for the attachment of the embryo, which occurs with the migration microenvironment for the attachment of the embryo, which occurs with the migration of fetal of fetal extravillous trophoblast cells to the decidua. Moreover, soon after implantation, the number of extravillous trophoblast cells to the decidua. Moreover, soon after implantation, the number of immune cells dramatically increases in the stroma of the decidua. In particular, the majority of first immune cells dramatically increases in the stroma of the decidua. In particular, the majority of first trimestertrimester human-decidual human-decidual leukocytes leukocytes areare naturalnatural killer killer (NK) (NK) cells, cells, followed followed by by myeloid myeloid cells, cells, T cells, T cells, andand rare rare dendritic dendritic and and B B cells cells [ 9[9–11].–11]. Figure 1. The immune response in placental tissues during fetal development. The first trimester of Figure 1. The immune response in placental tissues during fetal development. The first trimester of pregnancy is associated with a proinflammatory reaction which is necessary for implantation. In this pregnancy is associated with a proinflammatory reaction which is necessary for implantation. In this phase, placental tissues are characterized by a T helper 1 (Th1) proinflammatory environment. phase, placental tissues are characterized by a T helper 1 (Th1) proinflammatory environment. Natural Natural killer (NK) cells are involved in trophoblast invasion and support neoangiogenesis. A mixed killer (NK) cells are involved in trophoblast invasion and support neoangiogenesis. A mixed M1 and M1 and M2 macrophage population mediates a delicate balance for blastocyst implantation and spiral M2 macrophage population mediates a delicate balance for blastocyst implantation and spiral artery artery remodeling. The second trimester is characterized by a Th2, anti-inflammatory remodeling. The second trimester is characterized by a Th2, anti-inflammatory microenvironment microenvironment pivotal to fetal growth. T regulatory (Treg) cells, M2 macrophages, and NK cells pivotalsupport to fetal and growth. promote T regulatorythe survival (Treg) of the cells, fetus. M2 macrophages,As gestation andreaches NK cellsthe third support trimester, and promote an theinflammatory survival of theandfetus. Th1-type As immune gestation state reaches promotes the the third influx trimester, of immune an inflammatorycells into the myometrium and Th1-type immunewhich stateis crucial promotes to foster the labor influx and of delivery. immune cells into the myometrium which is crucial to foster labor and delivery. Between week 13 and week 27, the second trimester of pregnancy takes place. During this phase thereBetween is a shift week from 13 and the weekinitial 27, proinflammatory the second trimester to an ofanti-inflammatory pregnancy takes place.and T Duringhelper 2 this (Th2) phase thereresponse, is a shift aimed from at the preserving initial proinflammatory the fetal-placental to ansystem anti-inflammatory [12]. The tissue and microenvironment T helper 2 (Th2) is response, now aimed at preserving the fetal-placental system [12]. The tissue microenvironment is now enriched with Cells 2019, 8, 1401 3 of 22 M2-likeCells macrophages 2018, 7, x FOR PEER and REVIEW NK cells, whose interaction induces the generation of T regulatory3 of 23 (Treg) cells, keyenriched players with in M2-like sustaining macrophages fetal-maternal and NK tolerance cells, whose [13, 14interaction]. induces the generation of T Finally,regulatory in the(Treg) third cells, trimester, key players the in return sustaining to an fetal-maternal inflammatory tolerance and Th1-type [13,14]. immune state fosters labor andFinally, delivery. in the In third this trimester, phase, infiltration the return to of an immune inflammatory cells and into Th1-type the myometrium immune state is fosters crucial for promotinglabor and the contractiondelivery. In this of the phase, uterus, infiltration the delivery of immune of
Load more

Recommended publications
  • 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.
    [Show full text]
  • Local Immune Regulation in Human Pregnancy with Focus on Decidual Macrophages
    Linköping University Medical Dissertations No. 1016 Local immune regulation in human pregnancy with focus on decidual macrophages Charlotte Gustafsson Division of Clinical Immunology and Division of Obstetrics and Gynecology Department of Clinical and Experimental Medicine Faculty of Health Sciences, Linköping University SE-581 85 Linköping, Sweden Linköping 2007 © Charlotte Gustafsson 2007 Cover picture printed with permission from Articulate Graphics; www.articulategraphics.com Published articles have been reprinted with permission of respective copyright holder. Paper I © 2002 Blackwell Munksgaard Paper II © 2003 Blackwell Munksgaard Paper IV © 2006 Elsevier Ireland Ltd ISBN 978-91-85895-85-4 ISSN 0345-0082 Printed by LiU-Tryck, Linköping, Sweden, 2007 "There are no facts, only interpretations." Friedrich Nietzsche ABSTRACT During pregnancy, the woman carries a fetus partly foreign to her immune system, because of the expression of paternal antigens. Despite this, the fetus is normally tolerated and not rejected, as is often the case with organs in allogeneic transplantations. Systemic changes in maternal blood occur during pregnancy but, perhaps of greater importance, are changes in tissues locally in the uterus. The pregnant uterine endometrium, the decidua, is infiltrated by large numbers of leukocytes, mainly natural killer (NK) cells but also macrophages and T lymphocytes. Further, various cytokines are known to be secreted at the fetomaternal interface. However, the functions of these cells and the cytokine networks are not fully understood. The aim of this thesis was to investigate the local immune balance in normal human pregnancy decidua, both in the early phase of pregnancy and at parturition. First trimester decidual mononuclear cells, NK cells and macrophages were all shown to secrete IFN-γ, IL-4 and IL-10, as detected by ELISPOT.
    [Show full text]
  • From Trophoblast to Human Placenta
    From Trophoblast to Human Placenta (from The Encyclopedia of Reproduction) Harvey J. Kliman, M.D., Ph.D. Yale University School of Medicine I. Introduction II. Formation of the placenta III. Structure and function of the placenta IV. Complications of pregnancy related to trophoblasts and the placenta Glossary amnion the inner layer of the external membranes in direct contact with the amnionic fluid. chorion the outer layer of the external membranes composed of trophoblasts and extracellular matrix in direct contact with the uterus. chorionic plate the connective tissue that separates the amnionic fluid from the maternal blood on the fetal surface of the placenta. chorionic villous the final ramification of the fetal circulation within the placenta. cytotrophoblast a mononuclear cell which is the precursor cell of all other trophoblasts. decidua the transformed endometrium of pregnancy intervillous space the space in between the chorionic villi where the maternal blood circulates within the placenta invasive trophoblast the population of trophoblasts that leave the placenta, infiltrates the endo– and myometrium and penetrates the maternal spiral arteries, transforming them into low capacitance blood channels. Sunday, October 29, 2006 Page 1 of 19 From Trophoblasts to Human Placenta Harvey Kliman junctional trophoblast the specialized trophoblast that keep the placenta and external membranes attached to the uterus. spiral arteries the maternal arteries that travel through the myo– and endometrium which deliver blood to the placenta. syncytiotrophoblast the multinucleated trophoblast that forms the outer layer of the chorionic villi responsible for nutrient exchange and hormone production. I. Introduction The precursor cells of the human placenta—the trophoblasts—first appear four days after fertilization as the outer layer of cells of the blastocyst.
    [Show full text]
  • First Trimester Embryonic Nutrition
    First trimester embryonic nutrition Graham J Burton Centre for Trophoblast Research Department of Physiology, Development and Neuroscience Aims • To demonstrate that during the embryonic phase of development the human conceptus is supported by histiotrophic nutrition from the endometrial glands • To present evidence that the yolk sac is important for the uptake of nutrients during embryogenesis • To propose that the histiotrophic form of nutrition may protect the embryo from oxygen free radical mediated teratogenesis Human pregnancy is traditionally separated in to the embryonic and fetal periods Embryonic Fetal LMP Fert. 10 20 30 40 weeks Organization of the body plan, Growth and maturation differentiation of the major organs The teratogenic risk is greatest during the embryonic phase of development Sadler • Each organ system has a critical period depending on the timing of differentiation • It is critical that the intrauterine environment is stable during the period of embryogenesis The two sequential modes of nutrition for the conceptus The human uterus has approximately 15 endometrial glands per mm 2 • Nutrition of the conceptus is initially histiotrophic in all species - the uptake of oviductal and uterine secretions by the trophoblast • Later, in all mammals it switches to haemotrophic nutrition - exchange between the maternal and fetal circulations within the placenta Histiotrophic nutrition in early pregnancy WA Allen Endometrium Conceptus ‘Uterine milk’ Endoscopic view of a horse conceptus at approximately day 35 of pregnancy
    [Show full text]
  • Single-Cell Transcriptomics of the Human Placenta: Inferring the Cell Communication Network of the Maternal-Fetal Interface
    Downloaded from genome.cshlp.org on September 26, 2021 - Published by Cold Spring Harbor Laboratory Press Research Single-cell transcriptomics of the human placenta: inferring the cell communication network of the maternal-fetal interface Mihaela Pavličev,1,2 Günter P. Wagner,3,4,5,6 Arun Rajendra Chavan,3 Kathryn Owens,7 Jamie Maziarz,3 Caitlin Dunn-Fletcher,2 Suhas G. Kallapur,1,2 Louis Muglia,1,2 and Helen Jones7,8 1Center for Prevention of Preterm Birth, Perinatal Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio 45229, USA; 2Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA; 3Department of Ecology and Evolutionary Biology, Yale University, New Haven, Connecticut 06511, USA; 4Yale Systems Biology Institute, Yale University, West Haven, Connecticut 06516, USA; 5Department of Obstetrics, Gynecology and Reproductive Sciences, Yale Medical School, Yale University, New Haven, Connecticut 06510, USA; 6Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan 48201, USA; 7Center for Fetal Cellular and Molecular Therapy, Perinatal Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio 45229, USA; 8Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA Organismal function is, to a great extent, determined by interactions among their fundamental building blocks, the cells. In this work, we studied the cell-cell interactome of fetal placental trophoblast cells and maternal endometrial stromal cells, using single-cell transcriptomics. The placental interface mediates the interaction between two semiallogenic individuals, the mother and the fetus, and is thus the epitome of cell interactions. To study these, we inferred the cell-cell interactome by assessing the gene expression of receptor-ligand pairs across cell types.
    [Show full text]
  • Histological Expression of Metallothionein in the Developing Rat Placenta
    J Toxicol Pathol 2008; 21: 223–227 Original Histological Expression of Metallothionein in the Developing Rat Placenta Satoshi Furukawa1, Koji Usuda1, Masayoshi Abe1, Seigo Hayashi1, and Izumi Ogawa1 1Biological Research Laboratories, Nissan Chemical Industries, Ltd., 1470 Shiraoka, Minamisaitama, Saitama 349–0294, Japan Abstract: In order to clarify the metallothionein (MT) localization in the developing placenta, we histologically investigated the sequential MT expression in placentas and fetal livers using pregnant rats during gestation days (GDs) 9 – 21. The placentas were sampled and weighed on GDs 9, 11, 13, 15, 17, 19 and 21. In the early post implantation period, the expression of MT was slightly detected in the yolk sac and the primary decidual zone around the embryo. MT was then mainly present in the deciduas parietalis and yolk sac. After the deciduas parietalis ruptured, MT was subsequently detected in the yolk sac and deciduas basalis. MT continued to be detected in the yolk sac until GD 21, but it was reduced in the deciduas basalis in accordance with development of the fetal liver with elevated MT expression. In conclusion, the main expression site of MT changes from the maternal placenta to the fetal placenta, and then to the fetal liver in accordance with the fetal development. However, we speculate that the MT-positive cells in the placenta are positioned between the maternal and embryonic environments throughout the gestation period and always surround the embryo/fetus. (J Toxicol Pathol 2008; 21: 223–227) Key words: fetus, liver, metallothionein, placenta, rat Introduction fetal blood2. On the other hand, cadmium is known to accumulate in the placenta and induces cellular damage, Metallothionein (MT) is a family of cysteine-rich, low which can result in teratogenic or embryotoxic effects3.
    [Show full text]
  • The Function of the Decidual Cell
    the function of the decidual cell. 265 the function of the decidual cell. % W. E. Fothergill, M.A., B.Sc., M.D., Manchester. when stroma of the uterine mucous membrane, little to the eye o shape > faltered by pregnancy, presents 01 o\ a multitude of small cells, round 1?pt beyond ? and but little cell pro op , conspicuous nuclei ^ j?. of the uterine mu 'odified pregnancy, the stroma ?veatly by ce s a S ? different for many of the G P' appearance, Their are arSed and infinitely in shape. 1 they vary nuc e ' an(l with clear outline and . vesicular, ai ,vi?.e P . ^e their cell is abundant and gianu Ce> protoplasm of cas These are well seen in sections changes 1 m ^-on for m these *n oases of ectopic gestation, ofe^terusthe b) c uterine decidua goes on uncomplicated lQetal structures. the eonnec ^ has this of t; been maintained that enlargement of the uterine mucosa occurs only during gestation. d " ^ccdlsthat the so-called decidual cell" is according yp been rtrongyj, of This view, however, nas or?mC P^gnancy. ce Pposed; for cells from decidual indistinguishable morbid condit in the uterine mucosa in various is now ' membrane bv the formation of a decidual . s?nie to be from pregnancy possible, apart thateitieint t le this as it the fact remains, of fulC' may, ^ pfnsfant C6lls in of the Uterin6 mUC?Sa feat the stroma . ?? ??????? ? n ? ^le decidual cells in normal gestation wsaaat, my evp in work.work >>was called tQ the point while engaged moles and placenpathologi^l p UoK investigating fleshy the decidual cells^ awGd thafc> under certain circumstances, to an active in the changes play part i o foetus.
    [Show full text]
  • 17. Formation and Role of Placenta
    17. FORMATION AND ROLE OF PLACENTA Joan W. Witkin, PhD Dept. Anatomy & Cell Biology, P&S 12-432 Tel: 305-1613 e-mail: [email protected] READING: Larsen, 3rd ed. pp. 20-22, 37-44 (fig. 2-7, p. 45), pp. 481-490 SUMMARY: As the developing blastocyst hatches from the zona pellucida (day 5-6 post fertilization) it has increasing nutritional needs. These are met by the development of an association with the uterine wall into which it implants. A series of synchronized morphological and biochemical changes occur in the embryo and the endometrium. The final product of this is the placenta, a temporary organ that affords physiological exchange, but no direct connection between the maternal circulation and that of the embryo. Initially cells in the outer layer of the blastocyst, the trophoblast, differentiate producing an overlying syncytial layer that adheres to the endometrium. The embryo then commences its interstitial implantation as cells of the syncytiotrophoblast pass between the endometrial epithelial cells and penetrate the decidualized endometrium. The invading embryo is first nourished by secretions of the endometrial glands. Subsequently the enlarging syncytiotrophoblast develops spaces that anastomose with maternal vascular sinusoids, forming the first (lacunar) uteroplacental circulation. The villous placental circulation then develops as fingers of cytotrophoblast with its overlying syncytiotrophoblast (primary villi) extend from the chorion into the maternal blood space. The primary villi become secondary villi as they are invaded by extraembryonic mesoderm and finally tertiary villi as embryonic blood vessels develop within them. During the first trimester of pregnancy cytotrophoblasts partially occlude the uterine vessels such that only plasma circulates in the intervillous space.
    [Show full text]
  • Human Decidua Is a Major Source of Renin
    Human decidua is a major source of renin. K J Shaw, … , L Dubeau, W A Hsueh J Clin Invest. 1989;83(6):2085-2092. https://doi.org/10.1172/JCI114121. Research Article Plasma prorenin levels are elevated in normal pregnant women. Current evidence suggests renin production by tissues of the uteroplacental unit contribute to this elevation. The purpose of this investigation was to define the source of renin biosynthesis within the human uteroplacental unit and to characterize the renin produced. RNA extraction and Northern blot analysis consistently demonstrated renin mRNA expression in uterine lining both in the pregnant (decidua) and nonpregnant states (endometrium) and in fetal chorion laeve, which is inseparable from the decidua. In contrast, renin mRNA expression was not detected in basal plate and intertwin chorion (which is separate from decidua), amnion, myometrium, or placental villi. The total renin content in decidual homogenates was two- to threefold greater than in endometrial homogenates, and cultured human decidual cells produced significantly more total renin than cultured human endometrial cells, suggesting that pregnancy enhanced renin production by the cells lining the uterus. Immunoblot analysis and [3H]leucine incorporation identified 47,000-mol wt prorenin as the major form of renin produced by cultured human decidual cells. These studies indicate that maternal decidua is the major source of prorenin in the uteroplacental unit. Find the latest version: https://jci.me/114121/pdf Human Decidua Is a Major Source of Renin
    [Show full text]
  • Temporal Expression and Location of Colony-Stimulating Factor 1
    Proc. Natil. Acad. Sci. USA Vol. 86, pp. 8818-8822, November 1989 Developmental Biology Temporal expression and location of colony-stimulating factor 1 (CSF-1) and its receptor in the female reproductive tract are consistent with CSF-1-regulated placental development (c-fms protooncogene/placenta/uterus) ROBERT J. ARCECI*, FRANCES SHANAHANt, E. RICHARD STANLEYt, AND JEFFREY W. POLLARDtf tDepartment of Developmental Biology and Cancer, Albert Einstein College of Medicine, 1300 Moms Park Avenue, Bronx, NY 10461; and *Pediatric Hematology/Oncology, Dana-Farber Cancer Institute and Children's Hospital, 44 Binney Street, Boston, MA 02115 Communicated by Harry Eagle, July 31, 1989 (receivedfor review March 30, 1989) ABSTRACT During pregnancy the mouse uterine epithe- expression of CSF-1 and CSF-lR in the uterus and placenta lial synthesis of the mononuclear phagocyte growth factor throughout pregnancy. The data presented are compatible designated colony-stimulating factor 1 (CSF-1) is regulated by with a role for uterine CSF-1 in regulating both macrophage female sex steroids. To study the role of CSF-1 in the pregnant accumulation and the formation and differentiation of the female reproductive tract, the temporal expression and cellular placenta. sites of synthesis of CSF-1 and CSF-1 receptor (CSF-1R) mRNA were determined. CSF-1 mRNA, predominantly the MATERIALS AND METHODS 2.3-kilobase (kb) form, was first detected by in situ hybridiza- tion in uterine epithelium prior to implantation on day 3 and Animals and Cells. Adult female Schneider or C57BL/6 subsequently increased, reaching a peak at days 14-15. Its mice were paired with males.
    [Show full text]
  • Progesterone Withdrawal and RU-486 Treatment Stimulate Apoptosis in Speci®C Uterine Decidual Cells
    Cell Death and Differentiation (1997) 4, 76 ± 81 1997 Stockton Press All rights reserved 13509047/97 $12.00 Progesterone withdrawal and RU-486 treatment stimulate apoptosis in speci®c uterine decidual cells Bruce C. Moulton1,3, Joan Motz1, Cleo Serdoncillo1, the estrous cycle control both epithelial proliferation and cell Kamil C. Akcali2 and Sohaib A. Khan2 death (Sandow et al, 1979). Decreases in levels of estrogen initiate a wave of cell death (Pollard et al, 1987), (Nawaz et al, 1 Department of Obstetrics and Gynecology, University of Cincinnati College of 1987). Apoptosis of epithelial cells in ovariectomized mice Medicine, Cincinnati, Ohio 45267-0526 after estrogen priming was most effectively prevented by 2 Department of Cell Biology, Neurobiology and Anatomy, University of progesterone and estrogen treatment (Terada et al, 1989). Cincinnati College of Medicine, Cincinnati, Ohio 45267-0526 Early in implantation, luminal epithelial cells in the immediate 3 corresponding author: Department of Obstetrics and Gynecology, University of vicinity of the blastocyst undergo apoptosis initiated by Cincinnati, College of Medicine, Cincinnati, Ohio, 45267-0526, USA. tel: 513 558 8465; fax: 513 558 6138 e-mail: [email protected] unknown mechanisms (Parr et al, 1987). Adhesion of the blastocyst results in the decidualization Received 25.01.96; revised 01.06.96; accepted 18.06.96 of the endometrial stroma. Decidualization begins in the Edited by C.J. Thiele antimesometrial side of the uterus forming a primary decidual zone, expands to form a secondary zone in the antimesometrium, and eventually transforms stromal cells Abstract in the mesometrial region. During pregnancy, both decidual zones regress by apoptosis leaving decidual cells in the Progesterone secretion is required for the growth and mesometrial region to form the decidua basalis (Welsh, differentiation of endometrial stromal cells to form decidual 1993; Welsh and Enders, 1985).
    [Show full text]
  • Differentiation of Decidual Cells in Mouse Endometrial Cell Cultures
    Differentiation of decidual cells in mouse endometrial cell cultures S. C. Bell and R. F. Searle Reproductive Immunology Research Group, Department ofPathology, The Medical School, University ofBristol, Bristol S8 1TD, UJK. Summary. Mouse uterine cells were obtained by trypsinization of uteri at timed intervals after the induction of a decidual reaction by intraluminal instillation of arachis oil on Day 4 of normal pregnancy. Cells were also obtained from ovariectomized mouse uteri, some of which had received a progesterone\p=n-\oestradiol sequence to sensitize the uterus to a decidual stimulus. The differentiation of decidual cells was followed in cultures of these cells. The morphology of the cells obtained after 6 days in culture was dependent upon the seeding density employed. At low seeding density (plating densities of 75\p=n-\100cells/mm2) no net increase in cell number was observed, but large mononucleated stellate cells were present, with cytoplasmic and nuclear areas increased by 4-fold. At higher seeding densities (plating densities of up to 709 cells/mm2), a prolongation of cell survival and the appearance of substantial numbers of binucleated cells were observed. However, both cell types were characterized by the accumulation of filamentous material in the cytoplasm. Even at optimal seeding density the life-span of the decidualized cells could not be prolonged beyond 9 days. Uterine cells from hormone-treated ovariectomized animals underwent similar transformations but those from untreated ovariectomized mice gave only isolated islets of epithelial cells and scattered fibroblast-like cells in culture. These observations suggest that discrepancies in previous reports of in-vitro decidualization of rat uterine cells result from differences in the seeding densities employed.
    [Show full text]