Fertilisation + Implantation Flashcards
Where does maturation of sperm occur?
What does spermatozoa maturation consist of? (5)
Epididymis via androgens > Female reproductive tract
* 100 fold concentration of sperm (oestrogen-dependant)
* Completion of sperm modelling
* Changes in metabolism
* Acquisition of forward motion
* Changes in membrane surface proteins, charge and fluidity
* Coating of spermplasma membrane with glycoproteins
1- What is coitus?
2- What is the role of the parasympathetic nervous system in Coitus?
3- What is the role of the sympathetic nervous system in Coitus?
4- What is the role of the somatic nervous system in Coitus?
1- Sexual intercourse
2- Promotes vasodilation and erection of penile and clitoral tissues + lubrication
3- Vascular tone (constriction) in penile and and clitoral arteries + Emission of semen in urethra
4- Sensations following stimulation to glands penis / clitoris, Emission in internal urethra + Rhythmical contractions during ejaculation
1- During ejaculation where is sperm deposited?
2- Ovulated oocyte surrounded by cumulus oophorus is released from the ovary into…
3- Where does fertilisation usually occur?
1- Upper vagina near external os of the cervix
2- Peritoneal cavity, collected by fimbria of the fallopian tube
3- Ampulla of Fallopian tubes
Hurdle 1: Survival of spermatozoa in vagina.
1- What are the physical threats? How do we counter this?
2- How is environment of vagina a threat? How do we counter this
1- Physical loss of spermatozoa from the vagina
> Semenogelin I, Semenogelin II, Fibronectin
» Aggregate to form a coagulum = Forced retention of sperm in the vagina
- 20mins broken down = continue journey.
- Via Serine protease called prostate specific antigen
2- Normal vagina flora.. prevent opportunistic bacteria colonising … acidic environment . Secretes hydrogen peroxide + abundance of immune cells
> Neutralise and overwhelm defences
* Alkaline seminal fluid = neutralise
* Attenuation of vaginal immune response = immunosuppressive compounds
* The large number of sperm cells ejaculated = some will get in some will be sacrificed
* Sperm is deposited near the cervical os = close to cervix as possible
Hurdle 2: Penetrating the cervix
1- What is the problem? How do we counter this?
2- What makes up cervical mucus?
3- What does progesterone do?
1- Thick mucus
> Cervical crypts = allow pit stops for protection
2- Mucins > Muc5B , Muc4 + - Glycoproteins
- Stimulated by rising levels of oestrogen/ hydrophilic
3- Progesterone is released which increases cervical mucus secretion, therefore making it tougher and thicker - Oestrogen has opposite effect in Follicular phase as it hydrates mucus
Hurdle 3: Travel through the uterus
1- What mechanisms are involved in uterine transport of spermatozoa?
1-
* Tails = Self-propulsion of sperm
* Ciliated endothelial cells of endometrium create a current of fluid in uterine space
* Oestrogen-driven contractions of the myometrium towards the fundus during follicular phase (inhibited by progesterone) helping sperm move
* Female orgasm may help due to contractions
* Myometrial contraction stimulated via prostaglandins in seminal fluid
How does Capacitation support uterine transportation?
> How does it facilitate the acrosome reaction?
- Capacitation : loss of glycoprotein coat > reveals binding sites and receptors = increases receptivity to chemo-attractants + facilitate acrosome reaction .
- Changes in surface membrane properties > loss of membrane cholesterol which destabilised plasma membrane = facilitates acrosome reaction.
What is hyper activation how does it help with uterine transportation?
-
Increase in intracellular Ca2+ = activation of protein kinase A
> Activation of tails… detach from tubal endothelium and sperm pushed forward towards the egg for the acrosome reaction
Hurdle 4: Fallopian tubes
1- How do sperm know which Fallopian tube to go to?
1- Progesterone secreted by the dominant follicle helps to relax the muscles at the utero-tubal junction on the same side to the dominant follicle, therefore controlling sperm penetration and making it easier for the sperm to pass here
-Sperm have odorant receptors which get exposed during maturation (capacitation). As a result they can move in the correct direction towards the egg by reacting to the progesterone that it emits. (chemotaxis)
What happens to ovulated oocyte?
- What is the function of the Interstitial cells of Cajal
1- Moved from surface of ovary (in peritoneal cavity)
* Joins with Fimbriated ostium
2- Passes into the ampulla of the uterine tube
* Then Adheres to epithelium via the cumulus cells
3- Cumulus oocyte complex moves towards ampullary- isthmic junction
* Via Contractions of smooth muscle * Oviductalcilia
> Interstitial cells of Cajal (ICC)
* Regulators of oviductal motility, aware ovulation has occurred and are stimulated
Hurdle 5: Fertilisation
1- How does fertilisation happen?
1- Sperm hyaluronidases dissolve cumulus cell extracellular matrix of oocyte … Reaches Zone pellucida
2- Short lived binding of capacitated sperm to ZP3/ZP4 complex > increases intracellular Ca2+ due to activation of GPCR > exocytosis of acrosome enzymes = acrosome reaction
3- Enzymes : Acrosin, Hyaluronidases, Hexosaminidases DRILL into ZP
Hurdle 5: Fertilisation
1- What happens once the sperm cell has penetrated genetic material into the oocyte?
1- Triggers the exocytosis of Ca2+ from the Oocyte’s cortical vesicles and into the space just beneath the plasma membrane. This causes the zona pellucida to harden, preventing the entry of any other sperm cells (polyspermy). = Cortical reaction
2- Also induces the Oocyte’s second meiotic division, leading to the formation of a second polar body which lies next to the first polar body.
3- Genetic material of the sperm enlarges into a pro-nucleus and then fuses with the pro-nucleus of the ovum. They can only fuse AFTER the oocyte has undergone its second round of meiosis and expelled half of its genetic material
1- What factors enable Meiotic arrest of metaphase II?
2- What inactivates this pathway?
1- Maturation promoting factor (MPF) , Cytostatic factor (CSF)
2- Ca2+ calmodulin-dependent pathway.. MetaphaseII chromosomes decondense and Anaphase promoting complex activates
1- What is the name of the process by which the pro nuclei of the sperm and the oocyte fuse? What happens next.
2- Describe the different stages of preimplantation development?
- Syngamy > Zygotę > Ready to undergo mitotic division
- Zygote: This is the fertilized oocyte containing the fused male and female pro-nuclei. 24hrs post-fertilisation
-
Mitosis of cells: Zygote split into 2, then 4, then 8…
72hrs post-fertilisation -
Morula: This is a mulberry-shaped mass of 16+ highly polarised cells. The blastomeres undergo a process called compaction where the junctions between them begin to get more blurred
80-96hrs , 3-4days post-fertilisation -
Blastocyst: This contains around 32-64 cells. Characterised by blastocoel cavity > Fluid filled cavity in the centre with outer rim of trophoblast cells which form a trophectoderm. Also has an inner cell mass of pluripotent embyroblast cells.
120-15-hrs, 5-6days post-fertilisation
Hurdle 6: Maternal recognition of conceptus
1-What is the main problem that a conceptus could face at this stage of development?
2- What mechanism has been developed to prevent the destruction of a conceptus after fertilisation?
1- Could get destroyed by the maternal system .. foreign cells
2-
> The trophoblasts in the trophectoderm of the blastocyst secrete HCG (Human Chorionic Gonadotrophin)
> It can bind to the LH receptors on the luteal cells and maintain the corpus luteum (remains of a follicle which has released a mature ovum) and stop it from breaking down.
> This can therefore stimulate the production of progesterone and Oestrogen and prevent the break down of the lining, preserving it for implantation.
++Steroid secretion from corpus luteum prevents endometrium shedding and prepared uterus for incoming conceptus.
Hurdle 7: Implantation
1- What occurs during Hatching?
> Zona Pellucida (ZP )breaksdown
* Via Lytic enzymes in glandular secretions possibly activated by factor(s) from the blastocyst
- Hatching of the conceptus = rapid increase in size
Hurdle 7: Implantation
1- What is the first phase of implantation?
(Unstable interaction between blastocyst + uterine epithelium)
1- Apposition:
> Blastocyst rolls along the endometrium as a result of the L-selectin secreted by the Trophoblasts. It rolls along until it finds a receptive area for implantation
> Leukaemia Inhibitory Factor (LIF) cytokine released by the endometrial glands and is recognized by LIF receptors on the trophoblasts, therefore providing another recognition system for the implantation of the blastocyst. “come here” area.
Cytotrophoblast cells multiply and form what?
- Finger like projections in the syncytotrophoblast (chronic villi)
> Extraembryonic mesenchymal cells invade those projections > form foetal blood vessels
1- What is implantation window?
a- Days 1-7
b- Days 7-10
2- If no implantation what phase do we have?
1-
a- Days 1-7 - Luteal phase
Here the endometrium is very prereceptive. It has long apical microvilli, high surface charge and a thick glycocaclyx.
b- Days 7-10 - Receptive phase
The Pinopodes start to appear and there is a loss of the surface negative charge. There is shortening of the micro-villi and thinning of the mucin coat.
2- Refractory phase > resist attachment
What errors can occur from implantation?
- Ectopic Pregnancy: Implantation in the wrong place
- Miscarriage:
- Placenta Praevia: Placenta is over the internal os of cervix … haemorrhage
