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The Placenta of the Rat Comparative morphology of the placenta 29.08.2014 Cutting Edge Pathology 2014 2 Modified from: Chavatte-Palmer & Guillomot (2007) Comparative Implantation and

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  • The Placenta of the Rat Histology and Pathology

    Cutting Edge Pathology 2014

    Second Joint European Congress of the ESTP, ESVP and ECVP

    Dr. Maria Cecilia Rey Moreno

  • Comparative morphology of the placenta

    2 Cutting Edge Pathology 2014 29.08.2014

    Modified from: Chavatte-Palmer & Guillomot (2007)

    Comparative Implantation and Placentation;

    Bernirschke, Kaufmann & Baergen (2006)

    Pathology of the human placenta

    Diffuse

    Horse, pig, whale

    Zonary Cotyledonary Discoidal

    Ruminants Carnivores

    Human

    Monkeys (bidiscoidal)

    Rodents

  • General characteristics shared by all species

    3 29.08.2014

     Transient organ: supplies embyonal/fetal nutrition, growth and protection

     Vascular organ: close proximity of maternal and fetal vascular systems with large transfer

    contact surface between each other

     Interhemal membrane (placental barrier): separates maternal and fetal blood separated

    in their own compartments; site of transfer

     General functions: O2/CO2 transfer, water balance, synthesis and secretion of steroid

    hormones, paracrine and growth factors, metabolic and immunologic functions (immune

    tolerance)

     Origin: trophectoderm of the blastocyst

     Trophoblast cell: parenchymal cells of the placenta; different subtypes with different

    locations and functions

    Cutting Edge Pathology 2014

  • Gestational period and life-span of the rat

    placenta

    4 29.08.2014 Cutting Edge Pathology 2014

    1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 / 22

    Fertilization Implantation Birth

    days

    Placenta

    GD21/22

    Yolk sac

    Decidua

    Placenta

    Placentation

    Blastocyst

    Gestational

    day (GD) 5/6

    Trophectoderm→

  • Histology of the placental development

    in the rat

    5 Cutting Edge Pathology 2014 29.08.2014

    GD8 GD10 GD12 Non-pregnant uterus

    GD14 GD16 GD18 GD21

  • 6 Cutting Edge Pathology 2014 29.08.2014

    GD8/9: Decidualization and anastomosis

    of maternal vasculature

    Mesometrial side

    Mesometrial

    triangle

    Uterine

    lumen

    Antimesometrial side

    Decidua

    Implantation

    *

    *

    Decidualization (*): proliferation and

    differentiation of stromal cells

    Site of developing placenta:

    ectoplacental cone (EPC)

    Embryo

    Allantois

    Giant

    trophoblast

    cell

    Yolk sac

    Anastomosis of maternal vessels

    around the embryo

  • GD10: Yolk sac and placental

    cone differentiation

    7 Cutting Edge Pathology 2014 29.08.2014

    Ectoplacental

    Cone

    Yolk sac

    membrane

    Decidua

    (D)

    Chorion

    Uterus

    lumen

    2

    3

    D

    D Mesometrial triangle

    D

  • GD12: Chorio-allantoic placentation:

    interhemal membrane formation

    8 Cutting Edge Pathology 2014 29.08.2014

    Actin smooth muscle IHC:

    fetal blood vessel walls

    Morphogenesis of

    fetal vessels

    and maternal sinuses

    A

    C

    A: Allantois

    C: Chorion

  • 9 Cutting Edge Pathology 2014 29.08.2014

    First half of gestation:

    Uterine natural killer cells (uNK)

    Mesometrial triangle:

    sheaths of uNK (or granulated mesometrial

    cells) around spiral arteries

    GD10/12: Remodeling of spiral arteries

    GD10

    Second half of gestation:

    trophoblast cell invasion

    Decidua:

    Intravascular and interstitial trophoblast cell

    invasion; apoptosis of uNK

    GD12

  • GD10/18: Remodeling of spiral arteries

    10 Cutting Edge Pathology 2014 29.08.2014

    β-Actin:

    smooth muscle

    Cytokeratin

    Pan-26:

    trophoblast cell

    GD18 GD10

    GD18 GD10

  • 11 Cutting Edge Pathology 2014 29.08.2014

    Vimentin: fetal vessels

    GD14/16: Maturation of materno-fetal

    interhemal membrane

    HE

    Alignment of

    fetal vessels

    GD14

    GD14

    GD16

    GD16

  • 12 Cutting Edge Pathology 2014 29.08.2014

    GD18: Mature and fully functional:

    differentiation completed

    Fetal demands

    Efficiency

    Placental size unchanged

    Branching + dilation of fetal capillaries

    Thickness of interhemal membrane

    Remodeling:

  • Rat placenta at GD 21

    General characteristics

    13 29.08.2014

    Shape

    Interhemal membrane

    Fetal blood

    (capillary)

    Maternal blood

    (sinus)

    I

    II

    III

    I: Cytotrophoblast cells

    II + III: Syncytiotrophoblast

    Cutting Edge Pathology 2014

    Discoidal

    Hemotrichorial

    Interdigitation

    Labyrinthine

  • Rat placenta at GD 21

    General structure

    14 29.08.2014

    Kaufmann P., 2005

    http.//placentation.u

    csd.edu/rat.htm

    L

    T

    D

    UW

    UC

    UM

    Fetal side

    Maternal side

    SP

    MT

     Labyrinth (L)

     Trophospongium (T)

     Decidua (D)

     Uteromaternal channel (UM)

     Mesometrial triangle (MT)

     Spiral arteries (SP)

     Uterine wall (UW)

     Umbilical cord (UC)

     Yolk sac (YS)

     Amniotic membrane (AM)

    Cutting Edge Pathology 2014

    YS

    AM

  • Histology of the normal labyrinth at GD21

    15 29.08.2014

    Maternal sinus (M)

    Fetal capillary (F)

    Cytotrophoblast (C)

    Syncytiotrophoblast (S)

    M

    F

    S

    C

    Cutting Edge Pathology 2014

    Interhemal membrane

  • Histology of the normal trophospongium

    at GD21

    16 29.08.2014

    (L)

    Sp

    Gly

    (UM)

    Cutting Edge Pathology 2014

    Spongiotrophoblast cells (Sp)

    Glycogen trophoblast cells (Gly)

    Giant trophoblast cells

    Uteromaternal channel (UM), lined by parietal trophoblast cells (Pa)

    Pa

  • Histology of the normal decidua at GD21

    17 29.08.2014

    Spiral arteries (S)

    Glycogen trophoblast cells (Gly)

    Decidual cells (D)

    Uterine natural killer cells (uNK) (or granulated

    mesometrial cells)

    uNK

    Gly

    D

    Cutting Edge Pathology 2014

    S

  • Research by BASF SE

    18 Cutting Edge Pathology 2014 29.08.2014

    Birth Defects Research Part B (2013)

    98 3 208-221, 230-246, 247-259

  • Epoxiconazole (EPX)

    19 29.08.2014

     Inhibits CYP51 (lanosterol 14α-

    demethylase), a key fungal enzyme

    aromatase estradiol testosterone

    CYP 19

    CYP 51

    ergosterol lanosterol

    Epoxiconazole

     Antifungal agrochemical: azole

    class

     Proven effectiveness against

    fungi which resist other classes

     Inhibits CYP19 (aromatase) in

    mammals

    Cutting Edge Pathology 2014

  • 20 Cutting Edge Pathology 2014 29.08.2014

    Mechanistic studies with Epoxiconazole

    in rats

     Two Modified Prenatal Developmental Toxicity Studies (OECD 414) in rats

     Hormone measurements

     Hematology and clinical chemistry

     Pathology (organ weights, histopathology)

    Study 2 Study 1

    Administration of Epoxiconazole (EPX)

     Maternal adverse effects (↓ weight,

    ↓maternal serum estrogen, anemia, liver

    parameters altered, etc.)

     ↑ late fetal resorptions

     ↑ placental size

     Histopathological changes in placenta

  • Pathology:

    Material + Methods

    21 Cutting Edge Pathology 2014 29.08.2014

     Uterus extracted in toto

     Uterus opening at the antimesometrial

    side

     Placentas remained attached to the

    uterus

     Fixation: 10% neutral buffered formalin

    (24 - 48 h); transferred to 70% ethanol

     Trimming: transverse cut at the center

    of the disc (mid-sagittal section)

     Routine HE histotechnical processing

     Mean/median grading of

    degeneration/litter (statistical analysis)

  • Macroscopic findings

    22 29.08.2014

    Control

    Treated (50 mg/kg bw/d

    EPX)

    Late resorption Placenta with

    live fetus

    Cutting Edge Pathology 2014

    EPX : Epoxiconazole

  • Histopathology of the labyrinth

    23 Cutting Edge Pathol

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