Placental Development and Gestation Trophoblastic Disease Lecture (Dr. Cole) Flashcards

1
Q

Fertilization

A

Must be Preceded by:
1) Sperm Maturation (Epididymus)

2) Sperm Capacitation (Female Reproductive Tract) - Physiological changes necessary to Penetrate the Egg
- Removal of Some Epididymal and Seminal Glycoproteins

  • Increase in Membrane Permeability to Ca2+
  • Ca2+ Influx maximizes cAMP, Increases Sperm Motility
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Sperm Covering

A

EPIDIDYMAL:
- The Plasma Membrane of Epididymal Spermatozoa contains a Complement of Surface molecules (Proteins and Carbohydrates)

EJACULATED:
- The Surface Molecules in Epididymal Sperm become coated with SEMINAL PLASMA PROTEINS that mask potions of the Membrane Molecules

CAPCITATED:
- When Sperm are exposed to the Female tract Environment, these Seminal Plasma Coatings along with some of the Surface molecules are removed, thus exposing portions of the molecules that can bind to the ZONA PELLUCID of the Oocyte

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Three Mian Events in Fertilization

A

1) Acrosome Reaction
2) Sperm binding to ZP3
3) Sperm Egg Fusion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Acrosome Reaction and Sperm Binding to ZP3

A
  • The outer membrane of the SPERM binds to the ZP3 RECEPTOR and allows for the Acrosome reaction or the release of Enzymes (NEURAMIDASE and ACROSS) from the Acromosal Space of the Sperm to Break Down the Zona Pellucida
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Sperm- Egg Fusion

A
  • After the first Sperm fertilizes the Egg, Proteases released form the Cortical Granules present in the Egg remove OLIGOSACCHARIDES from ZP3 and partially cleave ZP2!!!!!!!!!
  • This process, called Cortical Reaction, prevents POLYSPERMY, an egg to be fertilized by more than one Sperm. POLYSPERMY results in NONVIABLE ZYGOTES
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Immunoglobulin superfamily protein IZUMO is required for Sperm to FUSE with eggs as is PROTEIN CD9 (Egg)

A
  • A mutation in IZUMO creates the INABILITY for the Sperm to Fuse to the Egg and undergo this Acrosome Reaction
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Cortical Reaction

A

FAST COMPONENT: Change in RESTING POTENTIAL of Oocyte Plasma Membrane prevents further binding of Sperm

SLOW COMPONENT: Release of Cortical Granules containing Enzymes (into PVS) that Destroy Sperm Receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Development of Blastocysts

A
  • Zygote undergoes Cleavage
  • Develops into MORULA, once it has attained a 8 cell number
  • Differentiates into BLASTOCYST, with outer Trophoblast, Inner Cell Mass and surrounding the BLASTOCYST Cavity
  • The Blastocyst hatches from its ZONA PELLUCID at 6 to 7 days
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Implantation of the Balstocyst

A
  • Hatch from ZP
  • APPOSITION: Adhesion to Endometrium
  • Trophoblastic and Endometrial Cells express ADHESION Molecules (Integrins)
  • Implantation mediated by PENETRATION TROPHOBLASTIC Cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Uterine Receptivity and Decimal Reaction

A
  • Corresponds to days 20 to 24 of a regular 28 day cycle
  • Optimal State of Endometrial Maturation for the Implantation
  • Consists in Vascular and Edematous Endometrial Strome, Secretory Endometrial Glands, and Apical Microprosesses, the PINOPODES, on the APICAL Domain of the Luminal Endometrial Lining Cells
  • Cell enlarge, become PALE Staining and STORE LIPIDS and GLYCOGEN under the Influence of PROGESTERONE!!!!
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Day 6 to 7: Blastocyst Implantation

A

1) Differentiated SYNCYTIOTROPHOBLASTIC CELLS invade part of the Myometrium (Interstitial Invasion)
2) Reduction in Number of DESMOSOMES facilitates Embryo Penetration

***PINOPODES are Apical Epithelial Cellular Protrusion of the Endometrium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Interstitial Invasion

A
  • Invasion of the ENDOMETRIUM and the Inner THIRD of the MYOMETRIUM
  • Determined by the action of Secretory Proteolytic Enzymes released by the SYNCYTIOTROPHOBLAST
  • Proteases erode the branches of the SPIRAL UTERINE ARTERIS to form spaces or LACUNAE of Maternal Blood within the SYNCYTIOTROPHOBLAST Mass
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Endovascular Invasion

A
  • Initiates the PRIMITIVE UTEROPLACENTAL Circulation and represents the Starting Point of the FUTURE INTERVILLOUS SPACE!!!!

***TROPHOBLAST Infiltration —> LACUNAE!!!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Uteroplacental Circulation

A
  • Established when Trophoblastic Cells are in DIRECT CONTACT with Maternal Blood
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

hCG

A
  • The SYNCYTIOTROPHOBLAST begins the Secretion of HUMAN CHORIONIC GONADOPTROPIN (hCG) into he MATERNAL LACUNAE
  • Secretion fo ESTROGEN and PROGESTERONE by the SORPUS LUTEUM is now under the control of hCG!!!!!!
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Role of DECIMAL Cells during Implantantion

A
  • The DECIDUA provides an IMUNE-PROTECTIVE environment for the Development of the Embryo
  • Produciotn of IMMUNOSUPPRESSIVE SUBSTANCES (Mainly PROSTAGLANDINS) to INHIBIT the activation of NATURAL KILLER Cells at the Implantation Site
  • Infiltrating Leukocytes in the ENDOMETRIAL STROM that secrete INTERLEUKIN-2 to PREVENT Maternal Tissue REJECTION of the Implanting Embryo
  • SYNCYTIOTROPHOBLASTIC Cells do not express Major Histocompatibility Complex Class II and cannot present Antigens to Maternal CD4+ T Cells!!!
17
Q

Formation of Primary Villi

A
  • At the end of the Second Week, CYTOTROPHOLASTIC Cells PROLIFERATE and extend into the SYNCYTIOTROPHOBLAST Mass, forming the PRIMARY VILLI
18
Q

Secondary Villi

A
  • Early in the Third Week, the EXTRAEMBRYONIC MESODERM Extends into the Primary Villi, forming the SECONDARY VILLI
  • In Cross Section, a Secondary Villus is formed by a core of Extraembryonic Mesoderm surrounded by a MIDDEL CYTOTROPHOBLAST Layer and an OUTER Layer of SYNCYTIOTROPHOBLAST
19
Q

Teritally Villi

A
  • Cells of the XE Mesoderm differentiate into Capillary and Blood Cells, forming the TERTIARY VILLI
  • The different between the Secondary and Tertiary Villi is the presence of CAPILLARIES in the LATTER
20
Q

The Placenta

A
  • Protect the Fetus
  • Provide Nutrition, Respiration, Excretion, and Hormone Protection during Development
  • Temporary Organ with Embryonic (CHORION FRONDOSUM) and Maternal (DECIDUA BASALTS) Components
21
Q

Functions of the Placenta

A

1) EXCHANGE OF GASES

2) TRANSFERS OF MATERNAL IMMUNOGLOBULINS:
- Maternal Ab, mainly Immunoglobulin G (IgG!!!!), are taken yup by the Syncytiotrophoblast and then transported to Fetal Capillaries for PASSIVE IMMUNITY

  • The Larger Immunoglobulin M (IgM) molecules DO NOT CROSS the Placental Barrier

3) RH (D Antigen) ISOIMMUNIZATION:
- Maternal Ab against D Antigen cause HEMOLYTIC DISEASE (Erythroblastosis Fettles)

  • Fetus is Rh-Positive, but the mother lacks the D Antigen (She is Rh-Negative)
  • Isoimmunization refers to Maternal Exposure and Sensitization to Fetal Rh+ RBC, mainly during DELIVERY
  • In a subsequent Pregnancy, Ab to D Antigens (IgG) cross the Placenta and cause Hemolysis of Fetal RBC
    4) STEROID HORMONE PRODUCTION: the Fetoplacental UNIT
22
Q

Decidua (Maternal Component)

A

1) DECIDUA BASALIS: That portion underlying the Implantation Site and forms the MATERNAL PART of the Placenta
2) DECIDUA CAPSULARIS: Portion overlying the Implanted Embryo and separating it from the Uterine Cavity
3) DECIDUA PARIETALIS: the remainder of the ENDOMETRIUM

23
Q

Villus Structure

A
  • The CHORIONIC VILLUS us the Basic Structure involved in Maternal- Fetal Exchanges
  • Each Villus has a Core of MESENCHYMAL Connective Tissue and Fetal Blood Vessels (Arterioles and Capillaries)
24
Q

Placental Barrier

A

(Outside to Inside)
1) Syncytiotrophoblast

2) Cytotrophoblast
3) Extraembryonic Mesenchyme
4) Fetal Endothelium

25
Q

Placentas

A

1) Bilobed
2) Circumvallate
3) Succenturinate (Exta Lobe)
4) Velamentous Cord (Cord pulled away from Palcenta a little)

26
Q

Clinical Consideration

A

1) Ectopic Pregnancy
2) Placental Abruption
3) Abnormalities of Placental Implantation
4) Uterine Atony
5) Placental Calcification

27
Q

Placental Abruption

A
  • The PREMATURE Separation of the Normally implanted Placenta is called PLACENTAL ABRUPTION
  • Hemorrhage into the DECIDEA BASALTS leads to premature Placental Separation and Bleeding
  • Separation of the Placenta from the Uterus IMPAIRS OXYGENATION of the Fetus
28
Q

Abnormalities of Placental Implantation

A

1) PLACENTA PREVIA:
- Implantation of the Placents OVER the Cervical OS

2) PALCENTA ACCRETA:
- Abnormal Trophoblastic Invasion
a) PLACENTA INCRETA: Inot the Myometrium

b) PLACENTA PERCERTA: Through the SEROSA and into the surrounding tissues

29
Q

Uterine Atony

A
  • The separation of the Placenta from the Uterus is determine by a cleavage at the DECIDUA BASALTS Region
  • After separation, the Placenta is ejected by STRONG Uterine Contractions, which also constrict the Spiral Arteris to prevent Excessive Bleeding
  • In Uterine Atony, the Contractions of the Uterine Muscles are not Strong Enough and Postpartum Bleeding Occurs
  • Predisposing factors of Uterine Atony include Abnormal Labor, substantial Enlargement of the Uterus, or Uterine FIBROIDS (LEIOMYOMAS)
  • Intravenous Infusion of OXYTOCIN stimulates Uteirn Contractions and Decreases the possibility of Uterine Atony
30
Q

Placental Calcification

A
  • Calcification is a sign of Placental Aging
  • The pattern of Calcification (Precipitation of Calcium Hydroxyapatite) is similar to that seen in other aging tissues
  • Probably a response to Cell Death and DIMINISHED Blood Circulation in localized Regions of the Placenta

One Significant risk factor: SMOKING!!!!!**

31
Q

Lithopedion

A
  • Fetal Death with an ECTOPIC Pregnancy (usually)

- The fetus is TOO LARGE to be REABSORBED by the body and CALCIFIES!!!!!!

32
Q

Gestation Trophoblastic Disease

A
  • A group of Neoplasms, both BENIGN and MALIGNANT, that arises from FETAL TISSUE INVADING the MATERNAL host
  • Tumos are composed of TROPHOBLASTIC Tissue
  • malignant GTD is diagnosed on the basis of Elevated Tumor Markers, primarily BETA- HCG!!!!!!!!!!!!!!!
  • GTDs are Highly responsive to Chemotherapy (Cure rate approximately 90%)
33
Q

Types of GTD

A

1) Complete Hydatidiform Mole: Benign
2) Partial Hydatidiform Mole: Benign
3) Invasive Mole (Chorioadenoma Destruens): MALIGNANT
4) Placental-Site Trophoblastic Tumor (PSTT): MALIGNANT
5) Choriocarcinoma: MALIGNANT

34
Q

Karyotype (Complete Mole)

A
  • NO FETUS!!!!
  • DIPLOID, but all CHROMOSOMES PATERNAL!!!!!!
  • Fertilization of Egg which has LOST its CHROMOSOMES by 2 Sperm or 1 Sperm that Replicated itself
35
Q

Karyotype (Partial Mole)

A
  • Fertilization of HAPLOID OVUM and Duplication of the Paternal Haploid Chromosomes or from DISPERMY!!!!!
36
Q

Complete Mole

A

KARYOTYPE:

  • 46 XX (> 90%), PATERNAL ORIGIN
  • 46 XY PATERNAL ORIGIN

PRESENCE OF FETAL TISSUE:
- ABSENT!!!!!!!!

HYDROPIC VILLI (Genomic imprinting is the Epigenetic Phernomtn by which Certain genes are expressed in a Parent-of-Origin-Specific Manner):
- EXTENSIVE: GRAPELIKE CLUSTERS are Diagnostic Characteristic (Poor or Absent Blood Vessels)!!!!!!

TROPHOBLASTIC HYPERPLASIA:
- Extensive with SIGNIFICANT ATYPIA

37
Q

Partial Mole

A

KARYOTYPE:

  • Triploidy (>90%)
  • Tetraploidy

PRESENCE OF FETAL TISSUE:
- PRESENT: Maternal Chromosomes Present

HYDRONIC VILLI(Genomic imprinting is the Epigenetic Phernomtn by which Certain genes are expressed in a Parent-of-Origin-Specific Manner):
- Limited and Focal

TROPHOBLASTIC HYPERPLASIA:
- Focal with MILD ATYPIA

38
Q

Malignant GTDs

A
  • 15 to 20% of Complete Moles develop Malignant Sequalea
  • INVASIVE MOLES invasion into MYOMETRIUM of Edematous Chorionic Villi covered with layers of Proliferative TROPHOBLASTIC Cells, BETA-HCG moderately elevated

***CHORIORCARCINOMA: Admixture of Malignant Cytotrophoblast and Syncytiotrophoblast, NO VILLI!!!!!!