[HD 201] E01-T08-Development of the Placenta_compressed

• The placenta consists of a fetal component (chorionic villi) and a maternal component (decidua basalis).
• Placental development changes coincide with embryo changes.

Placental Development

Hatching

• As the blastocyst implants, it remains surrounded by the zona pellucida.
• Once implantation starts, the blastocyst undergoes hatching, breaking free from the zona pellucida.
• If fertilization occurs then the trophoblast is exposed and can attach to adjacent structures.

Implantation

• After hatching, the blastocyst embeds in the endometrium at the embryonic pole (where the inner cell mass is located).
• Implantation begins at the end of the 1st week and is completed by the 2nd week.
• As the blastocyst embeds, the trophoblast differentiates into two layers:
  • Outer syncytiotrophoblast (no discernible cell boundaries)
    • Is a continuous multinucleate layer of protoplasm that secretes human chorionic gonadotropin (hCG).
    • hCG acts on the ovary to maintain the corpus luteum of pregnancy.
  • Inner cytotrophoblast (discrete cuboidal cells)
    • Is a mononucleated, mitotically active layer of cells.

Uteroplacental Circulation

• Lacunae (spaces) appear in the syncytiotrophoblast.
• The trophoblast erodes the uterine stroma and maternal blood vessels, especially dilated endometrial capillaries.
• Oxygen- and nutrient-rich blood from the eroded vessels gradually fills the lacunae, establishing uteroplacental circulation and initiating placenta development.

Abnormalities in Placentation

• Normally the placenta implants in the posterior uterine wall. Abnormal implantations are:
  • Placenta Previa: The placenta is low-lying and may cover the cervix.
    • Symptoms include painless vaginal bleeding, usually in the third trimester, with no associated increase in blood pressure.
    • Diagnosis is done via ultrasound.
    • A double setup (prepping for possible emergency caesarean section with internal examination) may be performed to diagnose placenta previa at term if the ultrasound examination could not be performed.
    • Vaginal delivery is impossible in placenta previa, often resulting in profuse hemorrhage and death of the mother and baby.
    • Placenta Previa Totalis: The placenta completely covers the os.
    • Placenta Previa Partialis: The placenta partially covers the os.
  • Placenta Accreta: The syncytiotrophoblast invades the myometrial wall.
    • Deep invasion prevents normal placental separation, sometimes requiring a caesarean hysterectomy.
  • Abruptio Placenta: Premature separation of the placenta from the uterine wall.
    • Occurs in patients with hypertension.
    • Symptoms include high blood pressure and a tetanically contracted uterus.
    • Premature separation leads to the death of the baby.

Changes During Implantation

• Two layers develop in the trophoblast: the syncytiotrophoblast and the cytotrophoblast.

Syncytiotrophoblast

• A continuous multinucleate layer of protoplasm with no discernible cell boundaries.
• Secretes human chorionic gonadotropin (hCG), which acts on the ovary to maintain the corpus luteum of pregnancy.
• Responsible for nausea and vomiting in the first trimester.
• It contains the hormones used in pregnancy tests.

Cytotrophoblast

• Inner layer of mononucleated cells that are mitotically active.

Pregnancy Status Serum HCG Levels (Nice to Know)

• As pregnancy increases in age, the HCG also increases significantly
• Values might double in a multiple-pregnancy
• The occurrence of nausea and vomiting is a good sign

Corpus Luteum

• The placenta partially covers the os when there is ovulation
• The Graafian follicle forms into a temporary endocrine gland called the corpus luteum
• If there is no pregnancy, it is called the corpus luteum of menstruation
• IF there is a pregnancy it becomes the corpus luteum of pregnancy
• Important source of progesterone needed to maintain pregnancy
• Transforms to a pregnant state because there is no placenta in the early weeks of pregnancy

Progesterone

• Secreted by the corpus luteum of pregnancy.
• Maintains the secretory endometrium necessary for pregnancy.
• Suppresses menstruation for the duration of pregnancy.
• Inhibits contraction of the uterine smooth muscle.
• Blocks the T-lymphocyte mediated immune response, which normally results from the baby acting on the mother.
  • The developing baby is considered immunologically to be an invader.

Inhibition of Implantation

• Administration of High Doses of Estrogen inhibits ovulation and interferes with the transport of the oocyte and sperm in the fallopian tube.
• It inhibits formation of the secretory endometrium.
  • For example the "Morning after pills"
    • Given 72 hours after or as soon as possible after unprotected coitus.
    • May be secondary to rape.

Intrauterine Device (IUD)

• A small, flexible plastic frame inserted into the uterus through the vagina using a speculum.
• Usually contains copper and can be left for months or years
• Check ups are still necessary to ensure correct placement and functioning
• Actions:
  • Prevents embryo implantation in the uterine wall.
  • Some IUDs contain progesterone that interferes with the formation of secretory endometrium inhibiting implantation.
  • May cause excessive bleeding during menstrual cycle.
  • Does NOT prevent pregnancy 100% of the time.

Decidua

• Gravid (pregnant) endometrium or gravid uterus (during pregnancy).
• Decidual reaction (aka decidualization): Changes in the uterine endometrium when implantation starts.
• Cells of uterine endometrium accumulate glycogen and lipids, leading to hypertrophy.
• Tissue with decidua means a recent pregnancy.

Functions

• Provides an immunologically privileged site for the conceptus to protect the developing embryo from the maternal immunologic response
• Decidual cells are phagocytosed by the syncytiotrophoblast, serving as nutrients for the implanted embryo.
• Protects maternal tissue from the uncontrolled invasion of the syncytiotrophoblast.

Parts

• Decidua Basalis: Directly beneath the blastocyst implantation or deep to the conceptus, where the implantation occurs. Contributes to the formation of the placenta.
• Decidua Capsularis: Overlies the conceptus (embryo) and initially separates it from the rest of the uterine cavity.
• Decidua Parietalis: Remaining parts of the decidua, named differently based on their relation to the implantation site.

Connecting Stalk

• Suspends the embryo in the chorionic cavity.
• Eventually develops into the umbilical cord.
• Chorionic membrane: Envelopes the chorionic cavity.
  • Outer syncytiotrophoblast
  • Middle cytotrophoblast
  • Inner extraembryonic mesoderm
• Chorionic plate: Extraembryonic mesoderm lining the inside of the cytotrophoblast.

Chorionic Villi

Embryo is completely implanted within the uterine wall Always passes through the three stages:

• Primary → Secondary → Tertiary
• None of the three stages are skipped during the development

Primary Chorionic Villi

Most primitive:

• Cytotrophoblastic cells become mitotically active and proliferate
• They push their way to the syncytiotrophoblast and forms the primary chorionic villi
• Develops in the entire chorionic sac or gestational sac Composition:
• Core of the cytotrophoblast
• Outer syncytiotrophoblast

Secondary Chorionic Villi

• Extraembryonic mesoderm pushes its way towards the center of the cytotrophoblastic core
• Produces a core of extraembryonic mesoderm
• Still surrounds the chorionic sac Composition:
• Outer syncytiotrophoblast
• Inner cytotrophoblast
• Mesodermal core

Tertiary Chorionic Villi

• Definitive Placental Villi
• Development of blood vessels or capillaries (before the end of the third week) in the secondary chorionic villi
• Developed via angiogenesis from the extraembryonic mesoderm
• Composition:
  • Outer syncytiotrophoblast
  • Inner cytotrophoblast
  • Mesodermal Core
  • Blood Vessels

Types of Villi

Stem of Anchoring Villi:

• Extends from the chorionic plate to the decidua basalis
• Also known as parenting villi
• First order of villi to form and where free villi originate from
• Does not participate in the exchange of nutrients
• Have several orders of branching (1°2°3°) Free or Terminal Villi
• Branching of the stem villi
• Arises from sides of the stem villi
• Where exchange of nutrients take place
• Will undergo the same changes (1°2° à 3°)

Intervillous Space

• When branching becomes complex, then the lacunae become highly complex
• Its primordium is the lacunae found in the syncytiotrophoblast
• The spaces between the villi

Changes in Chorionic Villi

• The decidua capsularis overlies the embryo and the decidua basalis lies deep into the embryo
• Chorionic villi (1º, 2º, 3º) cover the chorionic sac evenly until the beginning of the 8th week
• As the embryo grows older: Chorionic villi associated with the decidua capsularis gradually get smaller and disappear/degenerate due to the pressure the decidua capsularis imposes on one part of the chorionic sac Soon produces a relatively avascular bare area, the smooth chorion or chorion laeve Chorionic villi associated with the decidua basalis experience no pressure and thus gradually profuse and continuously proliferate Chorion Frondosum Contributes to the fetal development of the placenta Chorion Frondosum + Decidua Basalis = Placenta

Amniochorionic Membrane

• The uterine cavity gradually decreases in size as the pregnancy reaches term or as the embryo grows
• The uterine cavity is almost completely obliterated at the later months of pregnancy Changes in Decidua:
• In the early months of pregnancy, the decidua parietalis is completely separated from the decidua capsularis because of the uterine cavity
• As the pregnancy continues, these decidua will slowly meet In the later months of the pregnancy, these decidua are already adjacent to each other Function: Shock absorber where the fetus floats. Usually forms at the 8th week.
• En caul birth - the baby is delivered while still in the sac

Placenta

• The lacunae are filled with blood once the syncytiotrophoblast erodes the maternal blood vessels of the endometrium
• The development of the chorionic villi always goes through the primary, secondary, and tertiary stages. The cytotrophoblast cells push into the syncytiotrophoblast

Cotyledon

• Chorionic villi erode decidua basalis, NOT completely nor uniformly
• Non uniform erosion will leave wedges of the decidua called the placental septa
• These septa divides the placenta into cotyledons
• Placenta is composed of 20 to 25 cotyledons
• Each cotyledon contains 2 or more stem villi

Placental Anatomy

Gross Anatomy

• Discoid in shape, grounded, 20 cm diameter, thickest at center, tapers at the ends, weighs 500-600 grams
• Contains chorionic villi that will erode the endometrium non-uniformly, leaving wedges
• Formation of several placental septa between cotyledons
• By the end of 4th week, the decidua basalis is almost entirely replaced by the cotyledons
• The intervillous space has maternal blood vessels
• Maternal and fetal blood will never mix

Gross Anatomy (Maternal Side)

Cotyledons are visible = cobblestone appearance (visually has more "bumps" on this side) Presence of cotyledons separated by placental septa (grooves; black in Figure 28)

Gross Anatomy(Fetal Side)

Smooth and shiny Umbilical cord is centrally attached, with chorionic vessels radiating from umbilical cord Covers the Amnion

Amniochorionic Membrane

Can be separated into the amnion and the chorion The inner amniotic layer is thinner, covering the fetal surface of the placenta, and giving it its shiny appearance The chorionic membrane is the outer thicker layer, nearer to the maternal surface Between the two membranes is the obliterated chorionic cavity

Histology (Maternal Side)

Chorionic villi and intervillous spaces Highly cellular, cells are highly basophilic Darker in color The villi are more densely packed than the fetal side Spaces in between the villi are intervillous spaces Structures are usually observed at a higher magnification Decidua basalis Basophilic, enlarged cells because of glycogen and lipids Shows decidua cells as magnified on the lower right Intervillous space is found between the free villi structures

Histology (Fetal Side)

Easily determined to be the fetal side by the wavy amniochorionic membrane Usually seen as less densely packed villi More intervillous space Space in between the villi are the intervillous spaces

Circulation

Umbilical cord has two types of vessels: 2 umbilical arteries, and 1 umbilical vein (mnemonic: AVA) Endometrial arteries from the mother have very strong pressure The term pregnancy is 37 to 42 weeks Umbilical arteries carry carbon dioxide and waste materials of the fetus

• The blood exits out into the free villi
• This will then enter the intervillous space
• the blood is drained by the endometrial veins.

Placental Membrane

Placental membrane - where nutrients pass through to reach the blood vessels of the embryo Four barriers: 1st barrier: syncytiotrophoblast 2nd barrier: cytotrophoblast 3rd barrier: extraembryonic mesoderm 4th barrier: endothelium enclosing the blood vessels decrease in the number of cytotrophoblast cells. Syncytial knots The nuclei of the syncytium clump together Deposition of fibrin Occurs as the baby further develops

Amniotic Fluid

Functions Thermoregulation Lubrication Shock absorber Protects umbilical cord from compression from the fetal body parts Provides the necessary fluids, space, and growth factors to allow normal development of fetal organs such as the MSK system and pulmonary system Can also be monitored if there are congenital anomalies

Polyhydramnios

Amniotic Fluid greater than 500mL

Umbilical Cord

Examination of umbilical cord can also help in monitoring the progression of the pregnancy Three structures in the umbilical cord