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Week 1 3 Embryology Notes

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Embryology
-development from fertilisation to birth 38 weeks later Stages 1) Pre-embryonic development (wk1-2) a. Period of initial cleavage of zygote and implantation into the uterine wall and formation of the bilaminar embryo 2) Embryonic development (wk 3-8) a. Wehan all the major body systems are laid down and established b. This phase is time of rapid and dramatic developmental change 3) Fetal development (weeks 9-birth) a. When tissues and organs are formed during the embryonic phase grow and differentiate, mature so they are ready to function in postnatal life. Cell-cell interactions
-embryological development depends on inductive interactions between different cell/tissue layers-inductive process is interaction between non equivalent cell populations where the responding cells undergo a change in fate
-cell-cell interactions- direct contact via gap junctions, cell-cell contact, or production of diffusible factors
-inductive interactions- mesoderm induction, neural induction, limb bud initiation, nephron formation Congenital malformations
-3% of live births Causes
-environmental- teratogens- ionising radiation, drugs (thalidomide), viruses (rubells), maternal effects (metabolic disorders), trauma
-genetic-numerical defects (trisomy), structural defects (deletions, inversions, duplications)
-multifactorial- multiple genes and environment Gametogenesis malformations
-The absence of a specific chromosome in a gamete that combines with a normal gamete to form a zygote results in monosomy
-the presence of two of the same chromosome being present in a gamete that fuses with a normal gamete results in a zygote in trisomy

Down syndrome
-two copies of chromosome 21 fail to separate during either 1 st or 2nd meiotic anaphase of gametogenesis (nondisjunction)- half the gametes lack chromosome 21 whilst other half have 2 copies.
-If a gamete with two copies of chromose 21 fuses with normal gamete it results in trisomy 21 embryo
-symptoms: facial characteristics, short stature

Oocyte maturation
-during maturation, meiosis 1 (previously halted in first meiotic prophase) is completed and meiosis 2 is arrested in metaphase about 3 hours before ovulation.
-Birth control pill: oestrogen, inhibited ovulation by preventing secretion of FSH, LH from pituitary

1) FERTILISATION AND IMPLANTATION
- Viable spermatozoa surround ovulated oocyte in the ampulla of the oviduct, force their way through the cumulus granulosa of the oocyte
-when spermatozoon reaches the tough zona pellucidae (outer layer of the oocyte), sperm surface protein, SED1 it binds to glycoprotein receptors zp3 which triggers the acrosome of the sperm to release degradative enzymes that allows sperm to penetrate zona pellucid
-once a spermatozoon has penetrated the zona pellucid and reaches the oocyte, cell membranes of the 2 cells fuse. Membrane fusion results in
-Calcium wave that radiates over surface of egg from point of sperm contact, release of cortical granules that are located beneath the oocyte cell membrane into the perivitelline space, Between the oocyte and the zona pellicuda-the cortical granules release serine proteases that are released from cortical granules, these proteases destroy the protein link between the cell membrane and vitelline envelope, remove receptors that other sperm have bound to
-These two events alter the sperm receptor, making zona pellicuda impermeable by additional spermatozoa. These changes prevents polyspermy

-fusion of the spermatozoa forms the zygote (fusion of 2 gametes) and stimulates the ooctye to complete 2nd meiotic metaphase, anaphase and produces another polar body and the definitive oocyte. The chromosomes of oocyte and sperm are enclose in female and male pronuclei but membrane disappear as maternal and paternal chromosomes are replicated in preparation for first cleavage.
-Once fertilisation occurs, genes essential for embryonic development are silenced in the paternal genome whereas genes that are essential for placental development are silenced in the maternal genome. Silencing is mediated by DNA methylation. Prader-Willi syndrome- maternal copy of IGF-2 gene is imprinted (silenced), but a mutation in the paternal copy means that the gene is not functional. So no working copy of gene-symptoms, obesity, lack of eye coordination. Evidence: Two pronuclei implanted into pseudopregnant female mouse-develops as a trophoblast and gives rise to a mass of placental membranes-MOLE, two female pronuclei develop-small embryos with thin placenta-don't survivie to term Key stages in fertilisation
-restores the dipoloid number
-determines the sex of the baby, as the sperm either carries an X or Y chromosomes
-initiation of cleavage Zygote travels down the oviduct and undergoes cleavage
-once the oocyte is fertilised, the zygote undergoes cleavage- regulated series of mitotic divisions that are not accompanied by cell growth
-the large zygote subdivides into many small daughter cells known as blastomeres- the embryo doesn't change in size and is enclosed by zona pellucida. During cleavae, the embryo moves down the oviduct
-Up to the 8 cell stage the blastomeres remain totipotent- fertilisation can occur invitro, and the totipotent cells can be used for prenatal diagnosis
- By 4th day the embryo reaches the uterus consists 16-32 tightly aligned blastomeres which is called a morula Segregation of blastomeres into embryoblast and trophoblast precursors occurs in the morula
-at the 8 cell stage, the round, loosely adherent blastomeres begin to flatteninside-outside polarity-inner surface is concave, outer surface is convex where cell to cell contact among the blastomeres at the centre of mass is maximised

-at the morula stage: differential adhesion between different blastomeres results in segregation of some cells to centre of morula, inner cell mass, some blastomers are on the periphery of embryo- outer cell masss
-reorganisation of cells is known as compaction- activity of cytoskeletal elements and adhesion of blastomeres
-inner cell mass- embryoblast- gives rise to embryo proper
-outer cell mass- trophoblast- placental structures
-inside/outside hypothesis- differentiation of blastomeres based on their position- in the morula stage two transcription factors are expressed- oct4, nanog-inner cell mass expression maintained, but not trophoblast form Morula develops a fluid filled cavity and is transformed into a blastocyst
-4 days of developments, morula enters the uterine cavity which results fluid collecting between the blastomeres
-first, trophoblast differentiates into an epithelium- adjacent cells are tightly adherent to one another- due to cell adhesion protein E-cadherin, formation of intercellular junctions tight junctions( due to tight junctions fluid collects between inner cell mass), gap junctions, adherens junctions, desmosomes
-Trophoblast cells express basally poloarised na/K ATPase- pumps sodium into the interior of the morula- water follows by osmosis-blastocoelic fluid
-Hydrostatic pressure increases, blastocyst cavity forms
-blastocyst cavity causes the embryoblast cells (inner cell mass) to form a compact mass at one end of embryo and the trophoblast is organised into a thin, single layered epithelium
-embryo is a blastocyst- the side of the blastocyst containing the inner cell mass is called the embryonic pole of blastocyst and the opposite side is called the abembryonic pole. Blastocyst implants in the uterine wall on about day 6
-the blastocyst hatches from the zona pellucida on day 5, by enzymatically boring a hole in it and squeezing out
-the blastocyst tightly adheres to the uterine endometrium- uterus enters the receptive stage, apical glycocalyx decreases in amount of negative charge, apical microvilli flatten. Blastocyts express perlecan (heparan sulphate proteoglycans)these bind to ECM protein

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