Reproduction Module 4

Gestational age

From 1st day of a woman’s last menstrual period (LMP) to the age of pregnancy.

Fetal age

From the date of conception

Fetal age must be __ weeks less than gestational age.

*Onset menstruation is 14 days after ovulation

2

Why is gestation divided into 3 trimesters?

Clinical tracking with each 12-14 weeks characterized by a specific maternal physiological changes and fetal development stages.

1st Trimester

• Week of conception to 13th week of gestation

• All organ systems are being developed (before visibility)

• Mom: increased blood supply for nutrient and oxygen transport, and elevated HR

• Hormonal changes: fatigue, morning sickness, headaches, and constipation

2nd Trimester

• Week 13-26 of gestation

• Fetal organs continue to develop and uterus expands

• ~20: hair, nails, and reproductive organs are developed (sex), fetus starts to kick

• Bones and teeth continue to harden, and NS becomes functional

• Symptoms: body aches, dizziness (low BP), and swelling of hands and feet

3rd Trimester

• Week 27-birth (37-42)

• Fetus gains weight a slow grows lenghtwise

• Respiratory system matures just before birth

• woman visits healthcare / 2 weeks until last month were it is every week

What is checked during the maternal visits?

BP, urine samples for signs of urinary tract infections and other issues, and check cervix and the baby’s position (cephalic or breech).

Cephalic

Head-down

Breech

Bottom-down

Why are gestational weeks 3-10 so important? *1st trimester

Teratogens

What are examples of teratogens?

Radiation, alcohol, or certain prescription medications

Preterm

• Birth before 37 weeks

• maternal complications

• worsening health outcomes for baby the earlier

Full Term

• 37-40 weeks “optimal time”

• at 41 weeks = late term

Post Term

• More than 42 weeks

• risk for complications increase for both mom and fetus

• Obstetricians induce labour at 41-42 weeks

Postnatal Period or Pnerperium

• 6-week period after pregnancy

• Mom undergoes physical and psychological changes as the body returns to its pre-pregnancy condition

Naegele’s Rule

Calculating the delivery date assuming the gestational age of 280 days.

(Last day of LMP) - (3 months) + (1 year and 7 days) = Estimated Date of Delivery

What are the 2 stages of fetal development?

Embryonic and fetal

Embryonic stage

• first 8 weeks

• during 1st trimester

• major morphological changes with all organ structures being established “carnegie stages”

Carnegie Stages

Morphological changes of the embryonic period into 23 stages.

Fetal stage

• after 8th week (~10 weeks gestation, after Carnegie stage 23)

• final weeks of 1st trimester to birth

• growth and development of structure

Embryonic Period: Week 1-2

• First 2 weeks (preimplantation) zygote goes towards the uterine cavity for cleavage.

• Becomes a blastocyst

• After hatching from the zona pellucida the blastocyst implants into the uterine wall and develops the germ layers giving rise to organ systems

Embryonic Period: Week 3-4

• Mesoderm layer differentiates into muscle, kidneys, bones, and the heart

• Ectoderm layer differentiates into nervous tissues and skin

• Endoderm layer into digestive tract, lungs, and liver

• Primordial germ cells migrate towards the gonadal ridges

• Wolffian and Mullerian ducts form

• Early BV, RBV, and primitive heart appear in week 3.

• Week 4 -- primitive heart beats ~113 bpm first functioning organ of the embryo (only 2 chambers joined by contractile tubes)

In weeks 3-4 of the embryonic period the mesoderm layer differentiates into…

Muscle, kidneys, bones, and the heart

In weeks 3-4 of the embryonic period the ectoderm layer differentiates into…

Nervous tissues and skin

In weeks 3-4 of the embryonic period the endoderm layer differentiates into…

Digestive tract, lungs, and liver

Embryonic Period: Week 5

• 4 chambers heart are visible

• Upper and lower limbs bud from embryo and grow

• Cerebral hemispheres become visible

Embryonic Period: Week 6

• Primordial germ cells arrive and invade the gonadal ridges

• Heart and lungs descend to the thorax

• Heart starts to beat at a regular rhythm

Embryonic Period: Week 7-8

• Embryo transitions into fetal stage

• Fingers are visible

• Cartilage is replaced by bone

• Gonads differentiate

  • M -- primitive testes begin their descent

• Genitals are undifferentiated until week 9

Fetal Period (Week 9-birth)

• Begins after Carnegie stage 23 (~week 9 of gestation) and continues until birth

• Continued growth and development of the organs

• Fetus grows rapidly in length and weight

Fetal Period: week 8

Embryo tail disappears and is now called a fetus.

Fetal Period: week 11

lemon, all major organs have formed

Fetal Period: week 14

avocado

Fetal Period: week 21

grapefruit

Fetal Period: week 29

coconut

Fetal Period: week 38

watermelon

During which weeks is ultrasound monitoring?

18-22

Why do pregnant woman need ultrasound monitoring?

Visualize and evaluate specific fetal structures after all major organs have been developed (during 2nd trimester).

What are the different reasons and evaluations done during an ultrasound?

• Confirm pregnancy and location (detect ectopic)

• Confirm # babies in uterus

• Determine gestational age for due date and milestones

• Eval fetal growth with movement, breathing, and HR

• Eval placenta and fluid levels (amniotic to protect fetus)

• Identify birth defects

• Determine fetal position before delivery

• Other prenatal tests

 

Placenta

Temporary organs developed from both maternal and fetal tissues during pregnancy to help fetus development.

What does the placenta do?

• Nutrient

• Termo-regulation

• Waste

• Gas exchange (blood)

What are the 3 main types of placental structures and their species.

1. Epitheliochorial (cows, pigs, and horses)

2. Endotheliochorial (dogs and cats)

3. Hemochorial (humans, mice, and rabbits)

Epitheliochorial

least invasive, when maternal blood is seperate from fetal by 3 tissues: endothelium, CT, and epithelium

Endothliochorial

Maternal blood is separated from fetal membranes by layer of maternal endothelium and interstitial tissue.

Hemochorial

Human placenta allows fetal membranes to be bathed directly with maternal blood.

What are the primary functions of the placenta?

• nutrition + O2 exchange

• protection from xenobiotics

• hormone protections for maternal metabolism fetal growth and others

• excretion of waste

• attachment to uterine wall

When does the placental start to form?

Immediately at the invasion of the embryo. Embryo survives pre-implantation period and forms initial attachment to uterine wall -- placenta bury itself into the decidua.

Placental formation begins with implantation when the _________ or _______ layer (outer layer) initiates the attachment to the maternal decidua.

Day 9 post-fertilization, trophoblast cells grow and divide the decidua, anchoring and invading the uterine surface to try to reach and access the maternal BV.

trophectoderm, trophoblast

After initial invasion (~day 7 post fertilization), trophoblast differentiate into…

cytotrophoblast and syncyntiotrophoblast

Cytotrophoblast

• Inner layer of trophoblast cells

• Produces proteolytic enzymes to facilitate invasion of the decidua

• These cells replenish the cells of the outer syncytium layer "germinal cells of the syncytium"

• Has clear cell border and 1 nucleus

Syncyntiotrophoblast

• Composed of cytotrophoblast cells that fuse together into a multinucleate, continuous cell layer (w/o cell borders) --> syncytium

• Comprises the outermost layer of the trophoblast cells

• Actively migrates + invades the decidua

• Will become the blood-placental barrier

• As the layer expands, hollow spaces lacunae form and continue to grow where they will fuse to become intervillous space.

Explain the differentiation of the inner cell mass during invasion.

• Outer trophoblast layer differentiates and invades the decidua, inner structures of the blastocyst also develop

  • Inner cell mass = bilyered embryonic disc (epiblast and hypoblast)

• ~day 9 hypoblast gives rise to extraembryonic mesoderm (layer b/w outer cytotrophoblast and inner cell mass)

  • Supports the development of amnion, yolk sac, and chorionic villi of the placenta

What is chorionic villi?

Cytotrophoblast layer continues to grow and cells form finger-like projections through syncytium.

What are the stages of development for the chorionic villi?

primary, secondary, tertiary

These structures are the ones in direct contact with the maternal blood.

Primary, secondary, and tertiary villus

Primary villus

Form as the cytotrophoblast cells invade and protrude into the syncytiotrophoblast layer.

• Small and avascular.

• Cytotrophoblast core

• Surrounded by syncytium

Secondary villus

Extraembryonic mesodermal core

• Covered by cytotrophoblast cells + outer synciotrophoblast layer

Tertiary villus

Embryonic BV develop in mesodermal core develop forming this structure

• Extraembryonic mesodermal core with villous capillaries

• Covered by cytotrophoblastic and syntiotrophoblastic layers

How does the cytotrophoblastic shell form?

Cytotrophoblast proliferate laterally = cytotrophoblastic shell surrounding syncytiotrophoblast and entire embryo

• Anchoring villi = 3 villi connects shell to chorionic plate

  • These will grow villous branches "floating villi"

• Space b/w villi = intervillous space (b/w shell and plate)

• Where circulation will pool and bathe the chorionic villi.

• Plate + shell = surround embryo and form the chorion

How are asymmetrical villi formed?

• 1 and 2 villi project uniformly from the entire surface of the chorionic plate, however, 3 villi develop asymmetrically

• Grow to anchor sides of the embryo where is faces the maternal decidua

Chorion frondosum

highly villous area at the fetal side of the placenta

Chorion laeve

villi on the opposite side of the fetus that atrophy.

Decidua Basalis

Side where chorion frondosum attaches

Decidua capsularis

*doesn’t intereact with chorionic villi and later becomes smooth

Opposite side surrounding embryo

What is the function of the additional fetal membranes?

Extraembryonic membranes layers projecting from the placenta surrounding and protecting the development of the fetus

Additional fetal membranes: Amnion

• Innermost membrane surrounds embryo

• Transparent with amniotic fluid

• Protects embryo from mechanical stress + impact

Additional fetal membranes: Yolk sac

• Small sac on ventral surface of embryo

• Most important function in early prego

• Source of primordial germ cells and blood cells

• Regresses in later stages of prego

Additional fetal membranes: Allantois

• Hollow sac on tail end of yolk sac

• Contributes to nutrition and excretion

• Helps form umbilical cord

Additional fetal membranes: Chorion

• Outermost fetal membrane

• Surround all other membranes of the embryo

• Forms the fetal side of the placenta

• Includes chorion frondosum and chorion laeve

Additional fetal membranes: Extraembryonic coelom

Space b/w amnion and chorion.

Extravillous trophoblasts

highly invasive type of cytotrophoblast arising from the tip of anchoring villi.

Spiral artery remodelling

extravillous trophoblast migrating toward the decidua in endothelium towards maternal arteries causing modifications in myometrium.

Spiral artery remodelling steps

1. Early Pregnancy --> extravillous trophoblast proliferate from anchoring villi invading maternal decidua

2. End of 1st Trimester --> Extravillous differentiates into 2 types:

   1. Interstitial --> cell invade deeper into decidua and surround spiral arteries

   2. Endovascular --> cells penetrate the lumen of uterine spiral arteries

3. Midgestation --> both types of extravillous trophoblasts are involved in degradation of maternal vascular endothelium, and the replacement of SM + CT of arteries with fibrous material.

   1. Result = maternal spiral arteries become wider = decrease vascular resistance =  higher V of blood flow

4. 3rd Trimester --> blood supply to the uterus + placenta increases x10 factor compared t non-pregnant uterus (due to spiral artery remodelling)

What is the function of the placental circulation?

Acts as the interface b/w 2 circulatory systems: uteroplacental (maternal-placental) and fetoplacental blood circulation

Uteroplacental circulation

• Begins at the end of 1st trimester --- although maternal BV continue to be remodeled until 3rd trimester

• Blood flow from uterine spiral arteries --> intervillous space allows for exchange of O2 and nutrients b/w maternal blood and fetal BV (w/in chorionic villi)

• In-flowing arterial blood = push deoxy blood --> endometrial veins --> back into maternal circulation

Fetoplacental circulation

• Attached via umbilical cord

• Transports O2 + nutrients to and from the mothers blood w/o mixing.

• Umbilical cord has 3 vessels:

  • 1 umbilical vein --> carries oxygenated, nutrient from placenta -> fetus

  • 2 umbilical arteries --> carries deoxy, nutrient-depleted blood from fetus -> placenta

Maturation of the placenta

• Continues to grow in thick and circumference until end of 4th month of gestation

• Increased thick is due to length and branching of villi in chorion frondosum with expansion of the intervillous space

• After 4th month… no increase in thickness anymore, but as the fetus grows, the placenta circumference compensates.

The feto-placental barrier is made by what?

extraembryonic membranes and placenta

The feto-placental barrier is created by?

syncytiotrophoblast that enclose the intervillous space

What are the 2 functions of the feto-placental barrier?

1. prevent maternal immune rejection (immune tolerance)

2. protects the fetus from pathogens (via vaginal canal) ARE ABLE TO CROSS

hCG is produced by what?

Produced by trophoblast cells (especially syncyn.) shortly after develop and invade decidua.

What is the function of hCG?

Sub LH and survives corpus luteum to continue to produce E + P

Changes in sex hormones during pregnancy: 1st trimester

Embryo implantation = 5-6 after ovulation

Corpus luteum starts to degrade ~10 days after ovulation

hCG appears 10th day ovulation (4 days after implantation to stop corpus from degrading

Changes in sex hormones during pregnancy: 2nd trimester

12th week development -- placenta produces enough P + E to sustain

hCG decreases + corpus degrades b/w 13-17th week of gestation

Changes in sex hormones during pregnancy: 3rd trimester

Increased P + E until end of pregnancy

Other hormonal changes during pregnancy by the endocrine glands: anterior pituitary gland

2-3 fold englargement

Other hormonal changes during pregnancy by the endocrine glands: ACTH

determines the lengths of gestation and timing of parturition *some is produced by the placenta

Other hormonal changes during pregnancy by the endocrine glands: P + E

suppress FSH and LH production

Other hormonal changes during pregnancy by the endocrine glands: TSH

increase TH by 40-100% increasing maternal metabolic rate, meeting nutrient demands.

Thyroxine can cross the placenta for the first 12 weeks to maintain thyroid function.

Other hormonal changes during pregnancy by the endocrine glands: ovary

since FSH + LH are suppressed there is no ovulation

After birth it takes 2 months-1 year for hormonal cycle to be restaured

Other hormonal changes during pregnancy by the endocrine glands: Prolactin (PRL)

mammary glands to produce milk

proliferation of glandular epithelial cells + presecretory alveolar cells of breast growth

After birth this is burst in response to suckling.

Progesterone

prepares and maintains endometrium by increasing blood flow in uterine lining and thick cervix

Estrogen

increases steady throughout, responsible for physiological changes that maintains the normal pregnancy and prepares the uterus for parturition.

Physiological changes: mammary glands

• E + P + PRL, the breasts increase in size throughout pregnancy

• Ducts, alveoli and mammary epithelium undergo hyperplasia in prep for lactation.

• 1st milk = "colostrum" appears in alveoli of the acinar glands as early as 2nd trimester

Physiological changes: Uterus

• Uteroplacental blood flow x2 by mid-gestation due to spiral artery remodeling

• Uterus is stretched to accommodate the fetus, placenta, and amniotic fluid causing hypertrophy of muscle cells of myometrium

Physiological changes: Cervix

• Cervix softens due to CT remodeling

• Cervical glands x2 in # and create a mucus plug acting as a barrier to protect the uterine contents from infection

Circulatory system

• Cardiac output increases as early as 5 weeks of gestation

• CO increases 50% by mid-prego, as a result of increased HR + stroke V

• Increase in blood B + RBC mass

• Increase blood flow to placenta causes drop in total vascular resistance

• These changes begin to reverse as early as 2 weeks postpartum

Metabolic system

• Peak 3rd trimester -- phase of greatest fetus growth

• starts anabolic → catabolic directing nutrients to fetus

• Insulin resistance develops in early prego

• Late prego -- maternal adipose tissue releases FA for use in liver + muscle

  • Liver = metabolise FA -> ketones used in brain, muscle, and fetus

  • Also uses glycerol + AA -> synthesize glucose for the fetus

MSK system

• Lumbar lordosis

• Increased joint mobility due to ligamentous laxity, specifically in the sacroiliac joints (facilitate delivery)

• Stretch abdominal ligaments = diastasis recti

Immune system

• Trophoblast cells produce factors suppressing maternal immune response

• Immune tolerance prevents rejection of paternal antigens by the fetus

• Makes women more susceptible to infectious diseases and less susceptible to inflammatory diseases.

• uNKC secrete factors promoting early vascular remodelling and help fetal tolerance -- "critical for prego establishment"

• # decline at midprego, reaching normal levels at term