LR

22 Human Reproductive: Fetal Development and Embryology

Learning Outcomes

  • ALO1: Outline the early cleavage stages and the development of the morula
  • ALO2: Describe blastocyst formation and development prior to implantation
  • ALO3: Describe the processes of implantation and decidualization
  • ALO4: Outline the developmental stages of each trimester of pregnancy up to birth

Pre-Embryonic Cleavage

  • The first cleavage division of the zygote occurs immediately with a metaphase spindle forming and the diffuse chromatin becoming organised into distinct chromosomes.
  • Immediately anaphase and telophase is completed the cleavage furrow forms, and the one-cell zygote becomes a two-cell conceptus; this usually takes up to 24 hours from fertilization.
  • The process appears to be entirely under the control of maternal cytoplasm.
  • From early in the two-cell stage, the conceptus starts to express its own genes.
  • Division continues to 4, 8, and 16 cells (each cell is called a blastomere), though as the number of cells increases, the size of the conceptus remains the same due to the persisting zona pellucida.
  • As the conceptus passes towards the uterus, it begins to grow by continued cleavage.
  • Nutrients are absorbed from the secretions of the Fallopian tube.
  • Between the 8 and 16 cell stage, it undergoes compaction - individual outer blastomeres tightly adhere through gap and tight junctions and lose their individual distinction when viewed from the surface.
  • Now called a morula, a solid ball of cells.
  • The morula is propelled down the Fallopian tube by the ciliated epithelium and 3 to 5 days after ovulation the morula enters the uterus.
  • At the 32 to 64 cell stage (around day 4-6) the morula transforms into a blastocyst.
  • Blastocyst formed as secretions from endometrial glands enter the morula through zona pellucida.
  • At the 32 cell stage, the fluid collects between the blastomeres and reorganizes them around a large fluid-filled cavity called the blastocyst cavity or blastocoel.
  • Now the developing mass is called a blastocyst.
  • Although it now contains hundreds of cells, it is still about the same size as the original zygote.
  • The blastocyst floats free in the uterine cavity.
  • During this time, the blastocyst must make effective contact with the maternal endocrine system to change the ovarian cyclic pattern to a non-cyclic pregnant pattern.
  • The blastocyst contains two distinct types of cell:
    • Outer layer of trophoectoderm cells (trophoblast):
      • Surrounds the (inner) fluid-filled blastocoelic cavity
      • First of the extra-embryonic tissues--Do not contribute to the embryo/foetus.
      • Gives rise to part of an accessory foetal membrane the trophoblast of the chorion - a sac surrounds the foetus and the foetal portion of the placenta.
    • Inner cell mass (embryoblast) is asymmetrically placed within the blastocoelic cavity:
      • Eventually develops into embryo

Blastocyst

  • About day 5, the blastocyst “hatches” from the zona pellucida.
    • Mechanism involves digesting a hole in it with an enzyme, and then squeezing through the hole.
    • This step is necessary for implantation (attachment to the wall of the uterus).

Implantation

  • On day 6 or 7, the blastocyst positions itself to begin the process of implantation.
  • The location of the implantation site within the uterus tends to be characteristic for each species (typically in the posterior portion of the fundus or body of the uterus).
  • At the site of implantation, the blastocyst makes contact with the uterine tissue.
  • Trophoblast and the uterine endometrium epithelium come into contact, and the opposing microvilli interlock or fuse with one another - this is called attachment.
  • This close contact induces vascularization and differentiation in the underlying endometrial stromal tissue.
  • The next steps vary with each species but essentially there are two types of implantation - invasive and non-invasive.
  • Humans most other primates, dogs, cats, mice, rabbits, all have invasive implantation.
  • For successful implantation to occur, the endometrial wall of the uterus must be primed by the hormones oestrogen and progesterone.
  • 7 days after fertilization, blastocyst attaches firmly to uterine wall.
  • After attachment, the blastocyst is nurtured at first by uterine secretions, but this phase does not last long.
  • Within an hour of contact, it is clear that the stromal tissue of the endometrium has been affected.
  • Enzymes released by the trophoblast cells digest the endometrium.
  • As the blastocyst sinks into the endometrium, the trophoblast continues to erode the decidual tissue.
  • By day 14, the invasion will be complete, and the endometrium will grow over the blastocyst.

Nutrition and gaseous exchange of the embryo - placenta and umbilical cord

  • The embryo passes through 3 phases of acquisition of nutrition from the mother:
    • Absorption phase: Zygote is nourished by cellular cytoplasm and secretions in fallopian tubes/ uterine cavity.
    • Histoplasmic transfer: Before establishment of uteroplacental circulation, embryonic nutrition is derived from decidual cells and maternal blood pools that open up as a result of eroding activity of trophoblasts.
    • Hematotrophic phase: After 3rd week of gestation, substances are transported passively via intervillous space.
  • Humans have a chorioallantoic placenta that forms from the chorion and allantois.
  • Human placenta averages 22cm in length, 2-2.5 cm thickness (thickest at the centre) and weighs around 500 g.
  • Connects to fetus by the umbilical cord, approximately 55-60cm in length.
  • Contains 2 umbilical arteries and 1 umbilical vein.
  • Placenta begins to develop on implantation of the blastocyst – about week 4 - develops from the trophoblasts
  • Placenta grows throughout pregnancy. Development of the maternal blood supply to the placenta is complete by the end of the 1st trimester of pregnancy week 14.

1st Trimester (conception- 12 weeks)

  • From the 10th week of gestation, the developing embryo is called a fetus.
  • At the beginning of the fetal stage, the risk of miscarriage decreases sharply.
  • Typically, at the end of the 1st trimester, the fetus is around 30 mm in length crown to rump and weighs 8 g.
  • All major structures are formed by the 10th week, but they continue to grow and develop.
  • Because these major precursor organs are now formed, the fetus is not as sensitive to damage from environmental exposure.
  • Heart, hands, feet, lungs, brain, and other organs are present but have minimal operation.
  • Sex organs begin to appear during the third month of gestation.
  • Electrical brain activity is first detected at the end of week 5 - primitive neural activity rather than the beginning of conscious activity.
  • Uncontrolled twitches as muscles and brain develop.

2nd Trimester (13-27 weeks)

  • Synapses begin to form around week 17. Neural connections between sensory cortex and thalamus develop around 24 weeks but are not functional until around 30 weeks – minimal consciousness, dreaming, and ability to feel pain emerges.
  • Mother feels baby’s movements (typically in the 4th month, around the 20-21st week).
  • Development of organs and organ systems – almost complete by the end of the 6th month.
  • Nails harden and skin thickens, eye lashes and eye brows grow out, scalp hair appears during 5-6th month.
  • Meconium the first bowel movement has developed in the intestines.
  • Fetus visual and auditory senses are functional, fetus can make a sucking motion and scratch itself.
  • Sleep and awake periods regularly.
  • Bone marrow making blood cells.

3rd Trimester (28-40 weeks)

  • Rapid fetal growth – the majority of physical growth occurs in these last weeks of pregnancy.
  • Deposition of adipose tissue.
  • Major organ systems become functional.
  • 35-55 cm in length when born but large variation.
  • The control of purposeful voluntary movements continues to develop until puberty.

Organogenesis And Susceptibility To Teratogens And Fetal Loss

  • Most sensitive to teratogens = substance or influence that causes developmental defects

Ectopic Pregnancy

  • Ectopic pregnancy = development of embryo (up to week 8) or fetus (after week 8) outside of the uterine cavity.
  • Problems for mother are bleeding, acute abdominal or pelvic pain, rupture of the uterine tube (leading to death of the mother)