Fertilisation and pregnancy - reproduction 3 Flashcards
Fertilisation
Implantation
Placentation
Learning Objectives
* Fertilization and blastocyst development
* Process of Implantation and placental formation
* Activity of Key hormones
* Gestation and Maternal adaptations during
pregnancy
Fates of ejaculated sperm? 5
– Leak out of the vagina immediately after
deposition
– Destroyed by the acidic vaginal environment
– Fail to make it through the cervix
(mucus, anti sperm antibodies)
– Dispersed in the uterine cavity or destroyed
by phagocytic leukocytes
– Reach the uterine tubes
During fertilisation the sperm travels through what 3 parts?
Cervical canal, Uterus and Upper 1/3 of oviduct (fallopian tube)
How many sperm reach the fallopian tubes?
0.001% - Only ~100 reach the ampullary portion
of the FT where fertilization normally occurs
The female reproductive tract aids in migration via what 4 mechanisms?
- Thin cervical mucous (oestrogen from mature
follicle) aids sperm travel
*Contractions of myometrium – Sperm to
oviduct - drive sperm - Upward contractions of oviduct smooth
muscle drive sperm to egg - Allurin – Sperm chemoattractant released by
mature eggs to attract sperm towards it
When must fertilisation must occur?
Must occur within 24 hours after ovulation (viability of ovum)
How long can sperm last?
Sperm usually survive about 48 hours; can survive up to 5 days in female tract
What must the sperm undergo before they can penetrate the oocyte?
Capcitation
Capacitation is a cAMP mediated process what does it involve?
-> Ca^2+ influx which leads to this erratic whiplash motion developed by sperm which causes enhanced penetration of the ovum - not travelling in a linear way
-> Remove of surface proteins and cholesterol: weakening of sperm membrane allows readiness for penetration of outer layers for this acrosomal reaction (ability to fertilise an ovum)
How long must ejaculated sperm be “capacitated” in the female for fertilisation leading to activation of spermatozoa?
4-6 hours
Activation of spermatozoa - capacitation is mediated by what?
cAMP mediated process
Are ejaculated sperm capable of fertilisation?
Ejaculated sperm are incapable of fertilisation. They must be “capacitated” in the female genial tract
What is the corona radiata?
Corona radiata: layer of cells surrounding eggs
Receptors on head that recognise zona pellucida?
Z3 particularly but also ZP1,3+4 relevant in detection of egg whites - these are glycoproteins
Steps of sperm tunneling through the barriers surrounding an ovum?
5 Steps
- Fertilising sperm penetrates the corona radiata via membrane-bound enzymes in the plasma membrane of its head and bins to ZP3 receptors on the zona pellucida. (Zona Pellucida glycoproteins ZP1,3,4)
- Binding of sperm to these receptors triggers the acrosome reaction, in which hydrolytic enzymes in the acrosome are released into the zona pellucida.
- Acrosomal enzymes digest the zona pellucida creating a pathway to the plasma membrane of the ovum. When the sperm reaches the ovum, the plasma membranes of the 2 cells fuse.
- The sperm head with its DNA enters the ovum cytoplasm.
- The sperm stimulates release of enzymes stored in cortical granules in the ovum, which in turn, inactivates ZP3 receptors and harden the zona pellucida, leading to the block to polyspermy.
The 1st sperm to reach the ovum fuses with what and what does this cause?
Fuses with plasma membrane of ovum and the head of the fused sperm gradually pulled into ovum’s cytoplasm and this fusion triggers meiotic division of oocyte
Number of mechanisms of polyspermy - different between species paricualrly between sea urchin dvelopmental biology model but theya re differnet
Can more than 1 sperm fertilise an egg?
Diandritic triploidy resulting from dispermic fertilisation represents how many triploids?
Many cases where more then 1 sperm can fertilise an egg however if more than 1 is done normally it is unsuccessful and the embryos die
- Diandric triploidy resulting from dispermic fertilization represents 60−80% of human triploid
conceptuses (most die in embryogenesis)
2 Mechanisms to ensure monospermy?
Zona pellucida block and Membrane block
Mechanisms to block polyspermy are dependent on? This occurs in?
Ca2+ release from ER of oocyte in response to release of sperm head-associated phospholipase C zeta (PLCζ) into the egg’s cytoplasm
Occurs in waves in cytoplasm
Explain the zoda pellucida block mechanism to monospermy?
Ca2+ signal induces exocytosis of cortical granules
* Fusion of cortical granules with oocyte plasma membrane releases contents into the
perivitelline space (between the plasma membrane and the ZP)
* “Hardening” of zona pellucida - Increased resistance to proteolytic digestion and changes
in mechanical behavior
* Cleavage and modification of ZP glycoproteins
Explain the membrane block mechanism to ensure monospermy?
Not as well understood - Ca^+2 is involved however not just by itself - not independent there is more that they do not know
- Conversion of the membrane to a state that is unreceptive to sperm
- Lesser understood (Ca2+ elevation required but not sufficient alone to trigger membrane
block)
When fertilised ovum divides mitotically this causes formation of?
Is there cleavage of cells?
Totipotent yes or no and until when?
– Forms morula
– Cell cleavage (no increase in overall size)
– Totipotent up to 32 cell stage
How does the fertilised ovum divide during embryonic development?
Mitotically
Does blastocyst have a fluid cavity?
Yes, blastocyst has a fluid cavity
What are some maternal adaptations to?
1. Cardiac ouput?
2. Vascular resistance?
3. Renal and skin blood flow?
4. Weight?
5. Respiratory activity?
6. Urinary ouput?
7. Nutritional requirements?
- Cardiac output rises
Heart rate increases 10-20% (peaks by 32 weeks)
Stroke volume increases 25-30% (peaks at 16-24 weeks) - Systemic vascular resistance decreases 20%
Result of vascular and smooth muscle relaxation - Renal and skin blood flow increases
- Weight gain
- Respiratory activity increases by about 20%
– Increased tidal volume and minute ventilation - Urinary output increases
– Increase of GFR and Renal blood flow 30 - 60%
– Kidneys excrete additional wastes from fetus - Nutritional requirements increase
3 stages of implantation?
Apposition: blastocyst contacts the implantation site of the endometrium
Adhesion: trophoblast cells attach to the endometrial epithelium
Invasion: Trophoblast cells cross the endometrial
epithelial basement membrane and invade endometrial stroma
How long does it take for implantation to be completed?
Implantation is completed by the fourteenth day after ovulation
When does implantation begin?
Begins 6-7 days after ovulation, when the trophoblasts adhere to receptive endometrium
What is the decidua?
Sustained, specialized endometrium of pregnancy
How does the blastocyst implant in the endometrial lining?
By means of enzymes released by trophoblasts
Blastocyst implants in endometrial lining by means
of enzymes released by trophoblasts
1. Floats in uterus for how long?
2. This takes place when
3. The enzymes digest what and do what?
- Floats in uterus for ~72 hrs
- 6-7 days post-fertilization (secretory phase peaking)
- Enzymes digest endometrial tissue: Carve hole in endometrium for implantation of blastocyst
Trophoblast in adhesion has?
Ligand-receptor interactions
Bidirectional communciation
During invasion the trophoblast rapidly proliferates and differentiates into what 2 layers?
Inner cytotrophoblast and Outer syncytiotrophoblast
What happens during invasion? 4 points
- Fusion of cytotrophoblasts forms giant multinucleated cell
- Long protrusions extend among the uterine epithelial cells
- Protrusions secrete TNFα causing dissociation of these endometrial cells
- Protrusions can then penetrate the basement membrane of the uterine epithelial cells and
ultimately reach the uterine stroma.
- Endoderm layer becomes?
- Medoderm layer becomes?
- Endoderm layer becomes?
4 for each
- Digestive system, liver, pancreas and lungs (the inner layers)
- Circulatory system, lungs (epithelial system), skeletal system and muscular system
- Hair, nails skin, nervous system
What is the placenta?
Organ of exchange between maternal and fetal blood, the only disposable organ
Placenta acts as what?
What kind of organ is it?
It secretes what?
Acts as transient, complex endocrine organ that secretes essential pregnancy hormones: hcG+oestrogen+progesterone
Only disposable organ?
Placenta
What does the hCG: Human chorionic gonadotropin do?
Maintains corpus luteum until placenta takes over function in last two trimesters
Oestrogen and progesterone is essential for maintaining?
Normal pregnancy
What happens with placentation during week 2
- The trophoblasts come into contact with blood vessels creating?
Trophoblasts comes into contact with blood
vessels creating lacunae, spaces which fill with maternal blood.
Lacunae fuse to form lacunar networks - what happens here in placentation?
Maternal blood flows in and out to exchange
nutrients and waste products with the fetus – primitive placental blood supply
What part of placenta is the chorion?
Foetal part
Chorion is derived from?
Trophoblast and extra-embryonic somatic mesoderm
Chorion develop finger like villi which?
– Become vascularized
– Extend to the embryo as umbilical
arteries and veins
– Lie immersed in maternal blood
Cytotrophoblast begin to form primary chorionic villi which do what?
They penetrate and expand into the surrounding synyctiotrophoblast
What happens at week 3?
Extra-embryonic mesoderm grows into these villi, forming a core of loose connective tissue, at which point these structures are called secondary chorionic villi.
What happens at the end of week 3?
Embryonic vessels begin to form in the embryonic mesoderm of the secondary chorionic villi, making them tertiary chorionic
Cytotrophoblast cells of tertiary villi grow towards and spread across?
Cytotrophoblast cells of tertiary villi grow towards the decidua basalis of the maternal uterus
and spread across - called the Cytotrophoblastic shell
What are anchoring villi?
Villi connected to the decidua basalis through the cytotrophoblastic shell
What are the branching villi?
Villi grow outward from anchoring villi to provide surface area for exchange of metabolites between mother and fetus.
Slide 23
Week 4 1/2 can see structure of placenta
Key about maternal blood supply+foetal blood supply?
That the maternal blood supply+foetal blood supply don’t mix
After implantation what develops?
Chorion and amniotic cavity
What happens by week 5?
Placenta functioning, heart beating
By week 8 what is the embryo called?
Fetus
Placenta hormones:
Function of hCG: Human Chorionic Gonadotropin?
Maintain the corpus luetum of pregnancy
Stimulates secretion of testosterone by the developing testes in XY embryos
Function of Estrogen as placental hormone?
(Also secreted by the corpus luteum of pregnancy)
Stimulates growth of the myometrium increasing uterine strength by parturition and helps prepare the mammary glands for lactation
What is pregnant woman more susceptible to?
Woman becomes more vulnerable to other diseases/virus/sickness etc such as flu
Progesterone which is also secreted by the corpus luteum of pregnancy function as placental hormone?
Suppresses uterine contractions to provide a quiet environment for the fetus and promotes formation of a cervical mucus plug to prevent uterine contamination
Helps prepare the mammary glads for lactation
Hormone: Human Chorionic somatommatropin - function?
Believed to reduce maternal use of glucose and to promote the breakdown of stored fat (similar to growth hormone) so that greater quantities of glucose and free fatty acids many be shunted to the fetus.
Helps prepare the mammary glands for lactation (similar to prolactin).
Hormone - relaxin which is also secreted by the corpus luteum of pregnancy - function?
Softens the cervix in preparation for cervical dilation at parturition
Loosens the connective tissue between the pelvic bones in preparation for parturition
Placental PTHrp - parathyroid hormone related peptide
Increases maternal plasma Ca^2+ level for us in calcifying fetal bones if necessary, promotes localised dissolution of maternal bones, mobilising their Ca^2+ stores for use by the developing fetus.
How long for gestation from conception?
~38 weeks
Ovulation is prevented how?
Prevented by negative feedback effect of progesterone - prevents LH surge
What do progesterone levels rise from to during gestation?
From 30-150 nmol/L to about 500 nmol/L
What is the basis for pregnancy test?
rise in hCG secretion –
– Detectable in maternal serum/urine ~ 24hrs following implantation, ~ 9 days (basis of pregnancy tests)
hCG may also cause?
Morning sickness
The whiplash motility that Ca^+2 influx causes during capacitation causes a vigorous pattern of non progressive movement - what many this enhance?
May enhance penetration of the ovum
Fertilised ovum called?
Zygote
How long does it take for sperm and egg nuclei to fuse?
Within hour
When cells are totipotent, division of the morula
results?
Identical twins
Fraternal (non-identical) twins results from?
Fertilisation of 2 oocytes released during 1 cycle
Early Stages of Development from Fertilisation to Implantation
1. Day 4?
2. Explain what happens with blastocyst?
3. Day 5?
4. Day 6-7?
- Day 4 - Morula passes into the uterus
- Blastocyst – trophoblastic cells pull luminal fluid from the uterine cavity into the centre of the morula : Blastocoele
- Day 5 – “Zona hatching” - Blastocyst zona pellucida degenerates, replaced by the underlying layer of trophoblastic cells - can now interact with uterine wall and implant.
- Day 6-7 - Implantation
Trophoblast vs inner cell mass:
1. What do they both refer to?
2. Inner or outer cells of blastocyst?
3. Develops what?
4. Consists of?
5. Major function?
- Trophoblast refers to the layer of cells on the outside of the mammalian blastula whereas inner cell mass refers to the embryonic pole of the blastocyst
- T - outer layer and I - Innermost cells
- T - Develops the chorion and I - Develops the embyro
- T - Consists of tight cells and I - Consists of rounded cells
- T - Major function is the nourishment of the embryo by forming the major part of the placenta whereas I forms the body of the embryo
What happens to a zygote within 1 week of development?
Zygote grows and differentiates into blastocyst capable of implantation
What is trophoblast?
Outer cell layer of blastocyst which will become fetal placenta
What part of the blastocyst becomes the embryo?
The inner cell mass
What is blastocoele?
Fluid filled cavity of blastocyst that will become amniotic sac
- What point of contact of implantation is adhesion?
- Where does it appear to occur?
- How is correct orientation achieved?
- First contact
- Appears to occur at site where the zona pellucida is ruptured - possible for the cell
membranes of the trophoblast to make direct contact with the endometrium cell membranes. - Any point on trophoectoderm is can interact with the endometrium, then correct orientation (inner cell mass toward endometrium) achieved
by rotation of the inner cell mass within the sphere
What happens during adhesion stage of implantation?
Trophoblast attaches to uterine epithelium via microvilli and ligand-receptor interactions
Explain the ligand-receptor interactions during adhesion stage of implantation:
Integrins on blastocyst and
endometrium.
Heparin proteoglycans/heparan sulfate proteoglycans on surface of blastocyst, receptors on the uterine epithelial cell
What happens during invasion stage of implantation?
Trophoblast rapidly proliferate and
differentiate into two layers: Inner cytotrophoblast and Outer syncytiotrophoblast
Trophoblast differentiate into two layers during invasion stage of implantation - explain how this works:
- Fusion of cytotrophoblasts forms giant multinucleated cell
- Long protrusions extend among the uterine epithelial cells
- Protrusions secrete TNFα causing dissociation of these endometrial cells
- Protrusions can then penetrate the basement membrane of the uterine epithelial cells and
ultimately reach the uterine stroma
During invasion and implantation: embryoblast is formed - what happens at the beginning of week 2?
ICM divides into bilaminar disc: Hypoblast (primitive endoderm) and Epiblast (primitive ectoderm)
What does the hypoblast: primitive endoderm form?
Will form the primary yolk sac - for the transfer of nutrients between the fetus and mother.
What does the epiblast primitive ectoderm form and do?
Cavitate to form amnion - extra-embryonic
epithelial membrane covering the embryo and amniotic cavity.
The extra-embryonic mesoderm during invasion and implantation:
1. What is its origin?
2. Cells migrate between where?
3. Somatic lines?
4. Somatic form?
5. Visceral covers?
6. What cavity is between the layers?
- Origin unclear, probably from hypoblast
- Cells migrate between the cytotrophoblast and yolk sac and amnion.
- Extraembryonic somatic mesoderm lines the cytotrophoblast
- Extraembryonic somatic mesoderm also forms the connecting stalk (precursor of umbilical cord).
- Extraembryonic visceral (splanchnic) mesoderm covers the yolk sac.
- Cavity between the layers – chorionic cavity - precursor of gestational sac
Decidual (maternal) capillary walls is broken down by?
Expanding chorion
Maternal blood oozes through?
Spaces between the placental villi
Fetal placental capillaries branch off the umbilical arteries and project into where?
Into the placental villi
The fetal blood that is flowing through these vessels is separated from the maternal blood by what?
By only the capillary wall and thin chorionic layer that forms the placental villi.
Maternal blood enters through the maternal arterioles and then percolates through where?
Through the pool of blood in the intervillus spaces.
Physical changes within mother that meets the demands of pregnancy are what?
Uterine enlargement (weight x 20 excluding contents)
Breasts enlarge and develop ability to produce milk
Volume of blood increases 30%
The volume of blood increases by 30% during pregnancy what is increasing?
Red cell mass and plasma volume increases
Total body water increases during pregnancy due to?
Increased oestrogens and increased renin production: aldosterone
SEE SLIDE 27 DIAGRAM
