Human pregnancy and placenta development

• Pregnancy duration

  40 weeks, 240 days, 10 months. Full term is accepted as being approx. 38 weeks +
• Pregnancy counting

  Counted from Last Menstrual Period (LMP)
• Fertilisation/conception

  Approx. 14 days LMP
• Pregnancy development stages

  1. Preorganogenesis: 2-4 weeks LMP. Pre and perimplantation period

  2. Embryonic period: 3-10 weeks LMP: placental growth and organogenesis. (CRITICAL period)

  3. Fetal period: 11 weeks: cellular functionality and shaping, final structure formation
• Preorganogenesis = death
• Embryonic period= majority of defects, vulnerability major malfunction
• Major malfunction = red
• Sensitive= orange
• External risks in first trimester

  • Teratogen exposure
  • Drugs (recreational and medical) smoking
  • Alcohol
  • Workplace and environmental conditions
• Teratogen


  Something parent is exposed to that affect gestation
• Excess Vitamin A

  Affects pattern development
• Low folic acid


  Spina bifida
• Potential outcomes


  • Miscarriage
  • Fetal alcohol disorder – affects brain development
  • Small for Gestational Age (SGA)
  • Spina bifida – failure of neural tube closure
  • Limb and cardiac syndromes (thalidomide) - affect cardiac and limb development
  • Systemic syndomes: eg Rubella virus syndrome
• Spina bifida

  Failure to close neural tube. Most likely at spinal closure points at top and bottom of spine. Exposure to amniotic fluid causes degeneration of neural tissue in extreme cases. Mild cases: some vertebra haven't fused properly. Extreme: brain exposed
• Rubella virus


  German measles. Mild in adults (mild rash and itching). MMR prevents maternal contraction. Postnatal health problems: Cataract, glaucoma, bilateral deafness, congenital heart problems, mental and physical disabilities
• Early maternal changes: weeks 0-4

  1. Ovulation at d14. Insemination can occur several days pre or post ovulation.

  2. Early pregnancy factor detected in maternal blood at 2-3d post fertilisation (week 3 LMP) -inhibits the immune system

  3. Human Chorionic Gonadotrophin (hCG) is detectable early in week 4 (8d post-fertilisation)

  4. Week 4: embryo's hormones start supporting the corpus luteum- placenta will take over

  5. hCG insufficiency may lead to loss of pregnancy (58% attrition)
• Maternal changes

  • Organ squashing - Uterine expansion and fetal growth
  • Respiratory function increases - Tidal volume ↑ by about 200ml
  • Digestive problems - GI motility decreases (hormonal effects - progesterone)
  • Weight gain - Fetus, placenta, uterus, ↑Blood Volume (BV)↑ breast size, ↑ storage of protein and fat
  • Increased heart rate and stroke volume - HR ↑ by 10-15%, due to BV increase
  • Increased urination (micturition) and incontinence - Squashing of bladder, ↑ filtration rate, stress incontinence
  • Breast enlargement - Increase in Oestrogen promotes tissue development
• Gestational Trophoblastic Tumour


  "Hydatiform mole" parental input but not maternal input Overgrowth of trophoblast. Lack of genetic material to form embryo. Pregnancy growth look "bigger than stage"- fundus. Tumours Benign. Very rare cases can lead to choriocarcinoma
• Ectopic pregnancy


  Implantation in uterine tubes : "normal" pregnancy signs. Unilateral pain, displaced pain in shoulder, vaginal bleeding or brown discharge. Detected in ultrasound. Pregnancy has to be terminated. Tube rupture can be fatal
• Pre-eclampsia


  1. 5:100 (mild), 1:200 severe. From 20 weeks or post-birth. High blood pressure and proteinuria: headache, vision problems, vomiting and swelling. May cause pain below ribs. Pregnancy monitored. May induce early.
• Gestational Diabetes


  4 -5:100. Thirst, hunger, tiredness. Increased sugar in the urine. Elevated blood glucose (insulin resistance)
• Gestational Hypothyroidism


  2.5:100. Decreased TSH levels. Symptoms similar to normal pregnancy: tiredness, mood changes so difficult to detect
• Obstetric cholestasis


  1. 140. Pruritis (itching), leakage of bile salts into the blood stream. More common with multiple pregnancies.
• Gestational transient thyrotoxicosis


  1. 11:100. Persistent vomiting, weight loss, tremors. Increased T4(TH) levels as hCG stimulates T4 production. May resolve at 20 weeks. Associated with Hyperemesis Gravidarum (extreme morning sickness)
• Implantation

  1. Fertilisation results in a zygote

  2. Presence of protective layer (Zona Pellucida) until the uterus is reached

  3. Cell division increases the number of cells in the ball, not the size of the ball

  4. Ball of dividing cells is a Morula

  5. Blastocyst (a hollow ball) morula hallows out, hatches from zona pellucida for implantation

  6. Implantation between the secretory glands

  7. Implantation is more likely in the upper quadrants, if occur in lower sections placenta more likely to cover cervix

  8. Process begins with the attachment of the blastocyst to the uterine wall (approximately d6 post-fertilisation). Hyaluronic acid from blastocyst aids process

  9. Site of attachment: anterior or posterior uterine wall. Anywhere! Implantation is most likely to occur in the upper quadrants of the uterus

  10. Generally between secretory glands (uterus is in secretory phase)

  11. Spinal artery – become blood vessel of arteries

  12. Fully embedded (implanted) by d14 (d28 LMP)
• Implantation: different cell types d5-9

  1. As the blastocyst starts to implant , the structure is continuing to grow in complexity. The outer cells (trophoblast) start to differentiate and set up two layers : the cytotrophoblast and the syncytiotrophoblast

  2. Cytotrophoblast: More densely packed cells with more obvious cell structure. Will create the villi of the placenta

  3. Syncytiotrophoblast: Outer, invasive cells. Cells are not dense but "loose", so form gaps/holes. Lacunae (filled with blood). Creates the layer separating the fetus from the maternal blood.
• Developing the placenta day 9

  1. Vacuoles begin to form in the syncytiotrophoblast (Lacunae)

  2. Development of the extraembryonic membranes: Amniotic cavity expands, Formation of a yolk sac
• Placental function d13 (d27 LMP)

  1. Extraembryonic cavity grows and expands

  2. Mesoderm: crosses at umbilical stalk to line the extraembryonic cavity to create the chorion

  3. Syncytiotrophoblast produces human ChorionicGonadotrophin (hCG)

  4. Cytotrophoblast forms villi, invading the syncytiotrophoblast grow into intervillous lakes

  5. hCG takes over the role of supporting the Corpus Luteum. Progesterone (P) maintains the uterus and supports pregnancy.

  6. 42% survival to this stage
• Maturation of placenta

  1. Villi increase at the fetus to form the Chorion frondosum tree like structure to increase SA and create the placenta for exchange.

  2. Amnion and chorion fuse (amniochorionic membrane)

  3. Chorion laeve opposite the fetus is smooth and fuses with the uterine wall
• Placental circulation

  1. Maternal blood flows into intervillous lakes (not lacunae)

  2. Chorionic villi (Villous trees) grow into lakes

  3. Blood flows into these capillaries from the embryonic heart, via the umbilical arteries.

  4. Fetal blood picks up oxygen and nutrients from the maternal blood. Returns to fetus

  5. Fetal blood (Hb)has a higher affinity for Oxygen

  6. Fetal blood supply relatively deoxygenated

  7. Maternal and Fetal blood supplies ALWAYS separated by syncitiotrophoblast
• Placental function

  • Protection
  • Support growth of the fetus: Gas exchange (respiration), Nutrition, Waste exchange (excretion)
  • Hormone production: hCG (till ~20 weeks), Progesterone, Oestrogen, Placental prolactin, Placental lactogen (glucose availability), Relaxin (pregnancy accommodation and labour)
• Placental growth

  1. Maternal resources primarily support PLACENTAL growth in the first trimester. Resources to embryo are minimal.

  2. Placental function and growth is determined in first trimester.

  3. Increased weight gain and support of growth in last 2 trimesters comes from fetal growth. In the 1st trimester embryonic growth is relatively small: even though this the most vulnerable period of development.

  4. Problems in placental development may only become apparent after the first trimester when fetal demand on the placenta and maternal resources becomes significant.
• Maturation of the placenta

  • Placenta creates a semi-permeable barrier
  • Immune response occasionally initiated: resulting in an attack on fetal blood cells. Haemolytic disease of the fetus. When mother is Rh - and father is Rh +, resulting in Rh + baby. Rarely occurs now due to testing and treatment. Severe anaemia → oedema → hydrops (fatal)