Embryology Flashcards
What are the changes which occur to the genetic material of the egg/sperm following fertilisation?
- Sperm entry causes oocyte completion of meiosis II (extrusion of second polar body)
- Paternal pronucleus unwinds and enlarges
- Syngamy (following centralisation of pronuclei) occurs
- Metaphase plate established
What are the structural changes which occur during the first few cell divisions following fertilisation?
No growth; just division of totipotent cells:
- Increases nuclear to cytoplasmic ratio
- Restricted by zona pellucida
Compaction (creation of inner and outer cells):
- Morula forms (cluster of cells)
- Polarisation of embryo occurs (not all totipotent)
- Outer cells have E-cadherin (defines epithelium)
What is the blastocyst? How does the blastocyst form?
Blastocyst/coel = fluid filled cavity
- Created by tight junctions of outer cells causing ion gradient (Na+)
- Draws water in
- Trophectoderm becomes placental trophoblast
- Inner cell mass becomes embryo proper and placental mesoderm
Describe the stages of development from fertilisation to an early stage embryo:
- Fertilisation (syngamy) occurs
- Initial cleavage divisions
- Compaction (morula formation)
- Blastocyst formation
- Inner cell mass development
- Placental and embryo proper formation
How does the early embryo get to the uterus for implantation?
Regulation of ciliary beating (most significant):
- Stimulated to beat towards egg to help sperm (due to oestradiol)
- Then to beat towards uterus (due to progesterone)
- Blastocyst travels with cumulus cells
Other movement due to:
- Smooth muscle contractions
- Flow of tubular secretions
What are the different molecular markers found on the inner cell mass and trophectoderm? How do they arise?
Trophectoderm: Cdx2, Gata3, Eomes (Elf5 expressed)
Inner cell mass (ICM): Nanog; Gata6; Oct4 (Elf5 not-expressed as DNA methylated)
Occurs due to:
- Maternal gradients of mRNA (bicoid/dorsal etc..)
- Zygotic genome activation allows cells to respond based on their position
- Cell fate due to specific gene expression
- Sperm influence: pronucleus/pericentriolar matter and small non-coding RNAs
What are some mechanisms of epigenetic control on DNA? (5 examples)
- DNA methylation (turn gene “off”): E.g. Elf5 methylated in ICm but not trophectoderm
- Histone modification
- Non-coding RNAs
- Chromatin remodelers
- High order chromatin structures
How might the difference between a mule (male donkey; female horse) and a hinny (male horse; female donkey) be explained?
Unequal contribution of DNA methylation from sperm and egg
Imprinted genes:
- Silence gene copy depends on parent of origin (paternal IGF2 is always expressed)
X-inactivation (dosage compensation):
- Non-coding RNAs expressed by one X
- Causes other X to condense and silence its gene expression = Barr body formed
Why is implantation necessary? How is it achieved (general principle)?
Blastocyst needs to implant as it cannot self-sustain its growth (requires uterus)
Achieved through:
- Molecular and hormonal cross-talk between uterus and blastocyst
- Must both be morphologically and molecularly ready for implantation
What is diapause? How can it be achieved?
Prevention of blastocyst implantation until uterus is receptive:
- Coordinated with ovarian cycle
- Prolactin controlled to halt corpus luteum formation
- Increases survival chance by timing birth
Species dependent so can be achieved by:
- Facultative delayed implantation (behavioural): few days delay; implantation induced by suckling = mice/marsupials
- Obligatory diapause (environmental): week/month to coordinate with correct day length (deer)
What are the hormonal signals which allow implantation? How has this been shown experimentally?
Implantation requires both oestrogen and progesterone:
- Progesterone dominance with superimposed oestrogen window
- Oestrogen makes luminal cells responsive to blastocyst signals
Shown by:
- Ovariectomised rats (after pregnancy) given exogenous hormones allows implantation
- Oestrogen bump detected just before implantation
What are the changes which occur to the uterus to prepare for successful implantation?
Structural changes:
- Microvilli shorten
- Pinopodes activate (uterine walls move closer together)
- Endometrial glands form
Chemical Changes:
- Mucin expression decreases: mucin has negative change which would repel embryo
- Expression of epidermal growth factors (EGFs) and heparin binding (EGF-like) GF
- Leukaemia inhibitory factor (LIF) promotes endometrial receptivity (attracts blastocyst)
What is the decidualisation reaction and when does it occur?
Morphological and functional changes around the area of implantation (ONLY for invasive implantation!):
- Oestrogen ➡LIF ➡prostaglandin around implantation site
- Attracts leukocytes to area
- Increases vasculature surrounding (dilatation)
- Uterine stroma differentiates into decidua to provide lipids/glycogen as part of placenta
What chemical and morphological changes occur to the blastocyst to implant?
Hatching from zona pellucida:
- LIF produced by uterus induces strypsin
- Strypsin in a proteolytic enzyme to hatch
Binding molecules:
- Integrins (E.g ErbB) and cadherins on blastocyst expression induced by oesteopontin
- Bind HB-EGF on uterus
Why are pinopodes important? What is the evidence for their importance?
Determines the level of uterine fluids:
- Significant for multiple foetuses
Infertility caused by exogenous fluid injection
What are the different types of implantation?
Invasive implantation:
- Conceptus breaks through epithelium invading stroma (forms decidua)
- Embryo develops in uterine wall
- Uterine NK cells prevent blastocyst going too far
- Humans, cats, dogs, mice… (Mice have crypts to encourage implantation at particular points
Non-invasive implantation:
- Epithelium of endometrium maintained and becomes incorporated into placenta
- Blastocyst is larger (with more extraembryonic tissue) on implantation
- No decidualisation
- Pigs, sheep, cows, horses
What are the different mechanisms by which the corpus luteum is maintained in different species? Give species examples. (5 ways)
- Long-ovarian cycle: length = gestational period so no special changes needed (dogs)
- Neuro-endocrine link: act of mating causes hypothalamus stimulation (GnRH produced) causing ovulation (cats) or CL maintenance (mice)
- Luteotrophic factor secretion: Hcg produced by embryo to increase maternal progesterone (humans)
- Inhibition of luteolytic factors: E.g. pig embryo produces oestrogen to inhibit PGF2α
- Formation of accessory CL: pregnant horses secrete PMSG to stimulate second ovulation which then produces progesterone
How is maternal recognition of pregnancy achieved?
Maintenance of corpus luteum:
- Produces progesterone
Placental progesterone production:
- CL needed until placenta forms
What is a placenta? What are the functions of it and its attached tissues?
Close apposition of umbilical and uterine bloodstreams across the chorion for purposes of physiological exchange.
Functions:
- Supply of nutrients
- Supply of oxygen
- Immunological protection
- Protection from trauma (or teratogens)
- Hormone secretion (IFN-τ, hCG, steroids) E.g. insulin antagonising hormones
- Removal of waste
What are the extraembryonic structures during development? E.g. humans, fish
Surrounding layers:
- Shell and shell membranes (if applicable)
- Chorion (trophoblast cells)
- Aminon
Amnion houses:
- Yolk sac (nutrient rich)
- Embryo
- Allantois (facilitates gas exchange and absorption of waste products)
What are the different strategies by which embryos gain nutrients (give animal examples):
- Placentotrophy (absorption across foetal membrane): can be either haemotrophic (direct transfer between bloodstreams) or histiotrophic (uterine secretion absorption)
- Lecithotrophy: foetus gains nutrients from yolk sac and O2 from surrounding water/air
- Epitheliopathy: embryos eat specialised uterine wall (alpine salamander)
- Oophagy: eat unfertile eggs (great white shark)
- Embryophagy: eat sibling (fire salamander)
Why is progesterone important in the maintenance of pregnancy?
In establishing pregnancy/early embryo:
- Maintains uterine milk secretion until placenta forms
Controlling maternal physiology:
- Increases GFR to allow for increased waste excretion
- Insulin antagonising effect (diabetogenic)