Development and aging Flashcards
1
Q
What is the fertilisation age?
A
Measured from the time of fertilisation.
2
Q
Limitations of fertilisation age?
A
Difficult to know time of fertilisation exactly unless IVF.
3
Q
What is the gestational age?
A
Calculated from the time of the beginning of the last menstrual period.
4
Q
How is gestational age calculated?
A
Fertilisation date + 14 days. Early obstetric ultrasound and compare to embryo size charts.
5
Q
What is carnegie stage?
A
Based of embryo features not time. Use 23 stages of embryo development as reference.
6
Q
Advantages of carnegie stage?
A
Allows comparison of developmental rates between species.
7
Q
How many days of fertilisation age does carnegie stage cover?
A
0-60 days - Embryo development. After embryo develops into fetus.
8
Q
What happens during embryogenic stage?
A
Development of early embryo from fertilised oocyte. Formation of two population of cells. Pluripotent embryonic cells and extraembryonic cells.
9
Q
What do pluripotent embryonic cells contribute to?
A
Development of fetus.
10
Q
What do extraembryonic cells contribute to?
A
Support structures such as the placenta.
11
Q
When does the embryogenic stage take place?
A
14-16 days post fertilisation.
12
Q
What happens during the embryonic stage?
A
Establishment of germ layers and differentiation of tissue types. Establishment of body plan.
13
Q
When does the embryonic stage take place?
A
16-50 days post fertilisation.
14
Q
What happens during fetal stage?
A
Extensive growth to acquire fetal viability. Development of major organ systems. Migration of some organ systems to final location such as the reproductive system in males (testes).
15
Q
When does the fetal stage take place?
A
50 to 270 days post fertilisation.
16
Q
Stages in the few days spanning before and after fertilisation?
A
Ovulated oocyte to zygote. Cleavage stages from zygote to 8 cell embryo. 8 cell cleaved embryo to morula. Morula to blastocyst.
17
Q
What is a zygote?
A
Single cell with sperm and oocyte nucleus.
18
Q
When does the maternal to zygotic transition roughly take place?
A
4-8 cell stage.
19
Q
What is happening before maternal to zygotic transition?
A
Embryo is dependent on maternal mRNA’s and proteins. None of the embryo’s genes are being transcribed.
20
Q
When are the maternal mRNA’s and proteins used in the embryo during early embryo development produced?
A
Produced during oocyte development.
21
Q
What happens during the maternal to zygotic transition?
A
Transcription of embryo genes (Zygotic gene activation), increase protein synthesis, organelle maturation (mitochondria, Golgi).
22
Q
When does compaction take place?
A
8 cell stage or later.
23
Q
What happens during compaction?
A
Formation of 2 distinct population of cells (outer and inner cells). Outer cells connect to each other through tight gap junctions and desmosomes. This forms a barrier to diffusion between inner and outer cells of embryo (outer and inner cells exposed to different environments). Outer cells become polarised (formation of apical and basolateral domains).
24
Q
What happens after compaction?
A
Formation of blastocoel cavity.
25
How is the blastocoel cavity formed?
Formed by trophoblasts (outer layer) pumping Na+ into cavity to produced fluid filled cavity.
26
What is the layer of outer cells referred to as?
Trophoectoderm
27
What kind of a cells are in the inner cell mass?
Pluripotent embryonic cells.
28
What kind of a cells are in the outer cell layer?
Extra-embryonic cells.
29
Zona pellucida function?
Prevents polyspermy and protects early embryo.
30
How does the blastocyst hatch?
Enzymatic digestion and cellular contractions.
31
Why does the blastocyst hatch?
To escape zona pellucida and implant in uterine endometrium.
32
How does the blastocyst implant in the uterine endometrium?
Fusion of trophoblasts with uterine endometrium to form syncitiotrophoblasts. Forms interface between embryo and maternal blood supply.
33
When blastocyst implantation occurs, what are the two types of cells that the inner mass cells differentiate into?
Epiblast and hypoblast.
34
What will the epiblasts form?
Fetal tissues.
35
What will the hypoblasts form?
Yolk sac (extra-embryonic structure).
36
What are cytotrophoblasts?
Inner layer of trophoblasts. Interior to syncitiotrophoblasts.
37
How does an embryo ready itself for gastrulation?
Formation of new cavity called amniotic cavity. This forms a bi-laminar embryonic disc which separates the two cavities.
38
What is the amnion?
Epiblast cells migrate to form a thin membrane called the amnion that surrounds the amniotic cavity, separating it from the cytotrophoblast.
39
What is the bi-laminar disc made up of?
Epiblast and hypoblast.
40
Before gastrulation what is secreted from what cell that provide basis of pregnancy testing?
Syncitiotrophoblasts secrete hCG and beta hCG in blood/urine is detected in pregnancy test.
41
What is gastrulation?
Establishment of germ layers.
42
What does the primitive streak define?
Major body axis (cranial end and caudal end).
43
What happens at the cranial end of the primitive streak?
Expands to form primitive node.
44
What is the circular depression at the primitive node?
Primitive pit.
45
What is the primitive groove?
Depression along primitive streak.
46
What is the process of cells falling into the primitive groove called?
Invagination.
47
What cells fall into the primitive groove?
Epiblast cells.
48
What do the first cells to invaginate the primitive groove do?
Replaces hypoblast cells.
49
What do the first cells to invaginate the primitive groove form?
Definitive endoderm.
50
What are the cells don't fall through the primitive groove called?
Ectoderm.
51
What are the cells that don't fall fully through primitive groove called?
Mesoderm.
52
Where does the notochord form?
Along the embryo midline under the ectoderm (through mesoderm).
53
Function of notochord?
Organising centre for neurulation and mesoderm development.
54
What is neurulation?
Formation of neural tube and CNS.
55
How does formation of the neural tube happen?
Notochord signals direct the neural plate ectoderm to invaginate to form the neural groove. This create two neural folds that run along cranial caudal axis. Neural folds move together over neural groove and fuse forming a hollow tube. Migration of neural crest cells to other tissues.
56
What cells do neural folds contain?
Neural crest cells.
57
What is the neural plate?
Portion of ectoderm that is specified to become the neural ectoderm.
58
What is it called when there is a failure to close neural tube at head end? What can be seen in this condition?
Anencephaly. Absence of most of skull and brain.
59
What is it called when there is a failure to close neural tube at tail end.
Spina bifida.
60
What are neural crest cells derived from?
Ectoderm.
61
What are the 5 divisions of neural crest cells?
Cranial, Cardiac, trunk, vagal and sacral.
62
What do trunk neural crest cells form?
Dorsal root ganglia, sympathetic ganglia, adrenal medulla, aortic nerve clusters and melanocytes.
63
What do vagal and sacral neural crest cells form?
Parasympathetic ganglia and enteric nervous system ganglia.
64
What are somites?
Paired blocks of paraxial mesoderm.
65
Describe somitogenesis
Blocks of paraxial mesoderm condense and bud off in somite pairs with one of each pair on either side of the neural tube.
66
Where does somitogenesis start at?
Head end and progresses down long axis of the embryo.
67
What are the two types of tissue that somites form? What do these two types of tissue form?
Sclerotome and dermomyotome.
Sclerotome forms vertebrae and rib cartilage. Dermomyotome which forms dermatome and myotome.
Dermatome gives rise to dermis of skin, fat and connective tissue.
Myotome gives rise to muscles of the embryo.
68
What are the two folding processes that form the primitive gut? Describe each one
Ventral and lateral folding.
Ventral folding - Where the head and tail ends curl together.
Lateral folding - Where the two sides of the embryo roll.
69
How does ventral and lateral folding form the primitive gut?
Pinches off part of the yolk sac.
70
What are the 3 segments of the primitive gut?
Foregut, midgut and hindgut.
71
What are the first cells that are produced from gonadal cells in XY embryos?
Sertoli cells.
72
What gene drives male development?
SRY gene that is only present on y chromosome.
73
What gene drives female development in embryo?
Lack of SRY gene due to lack of Y chromosome.
74
What is major cause of early pregnancy loss?
Aneuploidy in embryo.
75
What kind of pregnancy increases exponentially in with maternal age?
Risk of trisomic pregnancy.
76
During oogenesis how many meiotic arrests are there?
2.
77
Why does aneuploidy of embryo increase with maternal age?
Loss of cohesin proteins between chromatids. This results in a loss in cohesion between chromatids. Chromatids can separate and drift during meiotic division leading to cells with wrong number of chromosomes during division of the cells.
78
What are the main cohesin proteins?
REC8 and SMC2.
79
What is an ectopic pregnancy?
Implantation of embryo at a site other than uterine endometrium.
80
Why can ectopic pregnancies be life threatening for the mother?
Can rupture and lead to severe internal bleeding.
81
Why does smoking increase risk of ectopic pregnancy?
Inhibits cilia function. Decreases contractility of the smooth muscle layer surrounding the fallopian tube. Smoking induces apoptosis of epithelial layer of fallopian tube by triggering expression of pro apoptosis proteins. Loss of epithelial cells results in loss of cilia and so embryo can't move down fallopian tube properly.
82
Risk factors for ectopic pregnancy?
Prior ectopic pregnancy.
Prior fallopian tube surgery.
Smoking.
83
Describe histiotrophic nutrition?
Nutrition derived from breakdown of endometrial tissue.
84
Describe haemochorial type placenta
Maternal blood is in direct contact with fetal membranes.
85
What is the chorion?
Outer membrane that surround the fetus while it is still being formed.
86
What is the connecting stalk?
Links developing embryo unit to chorion.
87
What are trophoblastic lacunae?
Large spaces filled with maternal blood formed by the breakdown of maternal capillaries and uterine glands.
88
What do trophoblastic lacunae become?
Form placenta by becoming intervillous spaces and maternal blood spaces.
89
What does the amnion form in the 5th week?
Fluid filled sac that encapsulates and protects the fetus.
90
What forms the chorion?
Yolk sac and trophoblast.
91
What do outgrowths of cytotrophoblast from chorion give rise to?
Chorionic villi.
92
What does fluid accumulation in amnion result in?
Contact with chorion forming the amniotic sac.
93
What are the 2 layers of the amniotic sac?
Amnion on the inside. Chorion on the outside.
94
What is the allantois?
Outgrowth of yolk sac that grows along connecting stalk from embryo to chorion.
95
What does the allantois develop into and how?
Becomes coated in mesoderm and vascularises to form the umbilical cord.
96
How are primary chorionic villi formed?
Cytotrophoblasts form finger like projections through synciotrophoblast layer into maternal endometrium.
97
Secondary phase of chorionic villi development
Growth of fetal mesoderm into the primary villi.
98
Tertiary phase of chorionic villi development
Growth of umbilical artery and vein into the villus mesoderm providing vascalature.
99
What kind of structure do terminal villus have and why is this important?
Convuluted knot of vessels. Covered with trophoblasts. Slows blood flow enabling exchange between maternal and fetal blood.
100
How does the thickness of cytotrophoblast layer around terminal villus change through pregnancy?
Decreases. Allows for faster exchange later on in pregnancy.
101
Maternal blood vessel branching before reaching endometrium
Uterine artery branches to give arcuate arteries. Arcuate arteries branch to give radial arteries. Radial arteries branch to give basal arteries. Basal arteries branch to give spiral arteries. Spiral arteries invade endometrium.
102
When do the basal arteries form the spiral arteries?
During menstrual cycle endometrium thickening.
103
What results in spiral artery remodelling?
Extra villus trophoblast cells invade down into maternal spiral arteries forming endovascular extra villus trophoblast. Endothelium and smooth muscle of blood vessels is broken down.
104
How are spiral arteries remodelled?
Opens up spiral artery to form low pressure, high capacity conduit for maternal blood flow.
105
How is oxygen exchanged across placenta?
Diffusion.
106
How is glucose exchanged across placenta?
Facilitated diffusion.
107
How are electrolytes exchanged across placenta?
Diffusion and active transport.
108
How is calcium exchanged across placenta?
Actively transported by magnesium ATPase calcium pump.
109
How are amino acids exchanged across placenta?
Active transport.
110
What cardiovascular and pulmonary changes occur in the mother during pregnancy?
Maternal cardiac output increases (stroke volume and heart rate increase). Maternal blood volume increases (greater number of erythrocytes and plasma). Pulmonary ventilation increases.
111
Where does gas exchange take place in the fetus?
Placenta.
112
How do the lungs develop in late fetal development?
Primitive air sacs form. Surfactant production begins and fetus makes rapid respiratory movements during REM sleep.
113
What does the pancreas of the fetus do in mid 2nd term?
Starts forming insulin.
114
What does the liver of fetus do as it moves towards end of pregnancy?
Build up glycogen stores.
115
What is meconium? What makes up meconium?
Meconium is the earliest stool of an infant. Amniotic fluid and bile.
116
What drives fetal organ maturation?
Corticosteroids.
117
Nature of labour?
Inflammatory. Immune cell infiltration, inflammatory cytokine and prostaglandin secretion.
118
What are the two phases of the first stage of labour?What occurs in the first stage of labour?
Latent phase - Slow dilation of cervix. Active phase - rapid dilation of cervix.
119
What occurs in the second stage of labour?
Maximal myometrial contractions to deliver fetus.
120
What occurs in third stage of labour?
Expulsion of placenta and fetal membranes. Post partum repair.
121
What is the cervix made out of?
Collagen fibres embedded in proteoglycan matrix.
122
Why does the cervix need to be remodelled?
Its stretch resistant and rigid at first. Needs to dilate later on in pregnancy.
123
How is the cervix remodelled for labour?
Softening in first trimester. Monocyte infiltration and IL6,IL8 secretion along with hyaluron deposition in weeks before pregnancy causing ripening. Dilation is caused by breakdown of hyaluron due to increased expression of hyaluronidases, MMP's break down collagen.
124
What hormone initiates labour?
Corticotrophin releasing hormone. Rises exponentially towards end of pregnancy.
125
What does corticotrophin releasing hormone from fetus do in labour?
Promotes fetal ACTH and cortisol release. Increase in cortisol induces positive feedback and drives placental production of CRH. Stimulates DHEAS production by the fetal adrenal cortex which is a substrate for oestrogen production.
126
Why do progesterone receptors on uterus switch when approaching term?
High progesterone maintains uterine relaxation. Expression of progesterone receptor B and C instead of progesterone receptor A. Progesterone receptor B and C are repressive isoforms and result in uterus becoming unresponsive to progesterone action.
127
What receptor in the uterus is expressed more nearer to term?
Estrogen receptor alpha.
128
What hormones does the uterus respond to nearer term?
Unresponsive to progesterone and sensitised to oestrogen action.
129
What stimulates oxytocin release in labour?
Stretch receptors and rising oestrogen levels.
130
What inhibits oxytocin receptor expression in early pregnancy?
High levels of progesterone. Keeps uterus relaxes early on.
131
What kind of receptor is the oxytocin receptor?
G-coupled.
132
What promotes oxytocin receptor expression near labour?
High oestrogen levels.
133
How does oxytocin increase uterine contraction?
Increase connectivity of myocytes in myometrium. Lower membrane potential threshold for contraction. Enhance liberation of intracellular calcium stores.
134
What are the primary prostaglandins involved in labour?
PGE2, PGF2alpha, PGI2.
135
What hormone drives prostaglandin action?
Oestrogen.
136
How does oestrogen drive prostaglandin action?
Activates phospholipase A2 enzyme which generates more arachidonic acid for prostaglandin synthesis. Stimulation of oxytocin receptor expression promotes prostaglandin release.
137
What is PGE2 involved in?
Cervix remodelling. Promotes leukocyte infiltration into the cervix, IL8 release and collagen remodelling.
138
What is PGF2 involved in?
Myometrial contractions. Promotoes connectivity of myocytes and reduces threshold for actional potential for contraction.
139
What is PGI2 involved in?
Myometrial smooth muscle relaxation to allow blood flow into uterus. (constant contraction wouldn't be good for blood flow)
140
Apart from steroid hormones and prostaglandins what other compounds are involved in cervix remodelling?
Relaxin and nitric oxide.
141
Where is DHEAS converted to oestrogen in labour?
Placenta.
142
Which part of the uterus to contractions start?
Fundus (top part).
143
How do myometrial muscles in the uterus form the birth canal?
Contractions start at the fundus and spread down. Muscle contractions are brachystatic - fibres do not return to full length upon relaxation. This causes lower segment and cervix to be pulled up forming birth canal
144
What occurs after fetal delivery?
Shrinkage of uterus. This results in folding of fetal membranes and area of contact of placenta with endometrium to shrink. Clamping of umbilical cord stops fetal blood flow to placenta which results in collapsing of villi and haematoma formation between decidua and placenta. Contractions expel placenta and fetal tissues.
145
Diagnosis of pre-eclampsia?
New onset hypertension and occurs after 20 weeks gestation. Severe headache present.
146
What is early onset pre eclampsia?
<34 weeks.
147
What is late onset pre eclampsia?
>34 weeks.
148
Risk factos for pre eclampsia?
Previous pregnancy with pre-eclampsia
BMI >30
Family history
Increased maternal age
149
What is eclampsia?
Severe complication of preeclampsia. Where high blood pressure results in seizures during pregnancy.
150
Pre eclampsia risks for mother?
Damage to kidneys, liver and brain.
151
Pre eclampsia risks for fetus?
Preterm birth due to placental abruption or pregnancy loss.
152
What is a placental abruption?
Separation of placenta from endometrium.
153
How do endovascular cytotrophoblasts contribute to development of pre eclampsia?
Endovascular cytotrophoblast invasion of maternal spiral arteries is limited to decidual layer. Spiral arteries are not extensively remodelled, thus placental perfusion is restricted.
154
What results in endothelial dysfunction in pre eclampsia?
Excess production of Flt-1 by distressed placenta leads to reduction of available pro-angiogenic factors in maternal circulation, resulting in endothelial dysfuction.
155
What is Flt-1 (Vascular Endothelial Growth Factor Receptor-1)?
Soluble receptor for VEGF (Vascular endothelial growth factor) which binds soluble angiogenic factors to limit their bioavailabliltiy.
156
What is placenta growth factor?
Pro-angiogenic factor released in large amounts by the placenta.
157
What tests can be used to determine risk of developing pre eclampsia?
sFlt-1/PlGF ratio or PlGF alone.
158
What is the only way to resolv pre eclampsia?
Delivery of the baby.
159
Treatments for pre eclampsia?
Anti-hypertensive therapies.
Corticosteroids for <34 weeks to promote fetal lung development before delivery.
160
How to prevent pre eclampsia?
Weight loss.
Exercise throughout pregnancy.
Low-dose asprin (from 11-14 weeks) for high risk groups.
161
Impacts on maternal health after suffering from pre eclampsia
Elevated risk of cardiovascular disease, type 2 diabetes and renal disease.
