Fertilisation and Implantation

Question 1

What processes must happen within spermatozoa maturation in order for a sperm to become fully functional?

Answer 1

Increase in concentration of spermatozoa
Change in metabolism ( increase in number of mitochondria)
Acquisition of forward motion
Membrane surface proteins, charge and fluidity changes
Coating of sperm plasma membrane with glyocoprotein

Question 2

What innervation is required for successful sexual reproduction?

Answer 2

Sympathetic activity by hypogastric nerve - increases vascular tone in penile and clitorial area, emission of semen in the urethra
Parasympathetic activity - pelvic nerve, promotes vasodilation and erecrtion, lubrication
Somatic outflow (pudendal nerve) - sensations from the glans penis/clitoris and emission in the internal urethra, results in reflex rhytmic contraction of muscle during ejaculation.

Question 3

During ejaculation where is the sperm depositied in the female reproductive tract.

Answer 3

Upper vagina near the external os of the cervix

Question 4

What three thigns must the sperm overcome in order to successfully fertilise an egg?

Answer 4

The vaginal environment
Penetrating the cervix
Travel through the uterus

Question 5

What are two ways that sperm can not survive the vagina?

Answer 5

Physical loss from the vagina
Death inside the vagina

Question 6

How does sperm ensure that it is not physically lost from the vagina?

Answer 6

Semen contains semenogelin and fibronectin which aggregate to form a loose gel to help retain sperm in the vagina
This gel is broken down within 20mins by prostate specific antigen (in semen) this allows sperm to regain motility are continue their journey
Roughly only 1% of sperm is retained in the vagina

Question 7

What environmental barriers does the vagina have against sperm?

Answer 7

Normal vaginal flora - create an acidic pH, prevent colonisation of pathogenic bacteria
Vaginal flora also secretes H2O2 and antimicrobial peptides
Abundance of immune cells.

Question 8

How are sperm adapted to survive the hostile vaginal environment?

Answer 8

Alkaline seminal fluid - neutralises the acidic vaginal environment
Prostaglandins, complement inhibitors and other immunosuppressive compounds decrease the vaginal immune response
Large number of sperms in the ejaculate overwhelems the innate immune response.
Deposited near the cervix - smaller distance to travel

Question 9

What features of the cervical mucus help sperm penetrate it to aid fertilisation?

Answer 9

Cervical crypts in the cervical canal - some sperm remain in crytps can be released over several hours.
Quality of cervical mucus - increased glycoprotein content, makes long, flexible and linear molecules, Muc5B and Muc4 - caused by rising levles of oestrogen,, are hydrophilic and thinnner for sperm passage
Mucosal grooves - secretion of mucus guides sperm into the cervix

Question 10

What happens during the follucular phase of the ovarian cycle that makes the cervix easier to penetrate?

Answer 10

Oestrogen relaxes the muscles of the cervix
Increases secretion and hydration of cervical mucus, allows sperm penetration into the uterus

Question 11

What happens to the cervical mucus during the luteal phase?

Answer 11

Progesterone decreases cervical mucus secretion and hydration levels
Becomes thicker and more yellowy in appreanced, sperm and pathogens unable to penetrate, protects the potentially fertilised embryo

Question 12

What is spinnbarkeit cervical mucus testing?
How does this link to Billing’s method?

Answer 12

Spinnbarkeit cervical mucus is the cervical mucus just prior to ovulation, this is clearer, thinner and more stretchy so allows easier penetration of sperm.
Bilings method uses analysis of cervical mucus to identify when you are at your most fertile as a method of family planning
Changes in mucus is related to the arrangement of the glycoprotein network.

Question 13

What three mechanisms help transport spermatozoa in the uterus?

Answer 13

Self-propulasion of sperm
Ciliated endothelial cells of endometrium create a current of fluid
Oestrogen-driven contraction of the myometrium towards the fundus during the follicular phase.
Female orgasms - aids sperm retention due to uterine wall contractions
Prostaglandings in semen - also stimulate myometrium contraction

Question 14

What is capacitation of the sperm?

Answer 14

The process sperm go through after ejaculation in order to be able to fertilse an egg
Loss of glycoprotein coat on plasma membrane to reveal binding sites and receptors e.g
Epididmyal protease inhibitor - helps coagulate sperm
Allows acrosome reaction
Increases sperm receptivity to chemo-attractants.
membrane becomes more permeable to Ca2+
These changes may be due to secretions from the uterus wall

Question 15

What changes occur in the cell membrane of the sperm after ejaculation to intiate the acrosome reaction?

Answer 15

Loss of membrane cholsterol destabilised the plasma membrane

Question 16

How do sperm become hyperactive after ejaculation?

Answer 16

Increase in intracellular Ca2+
- intiates whiplashing tail beats
- Activates protein Kinase A needed for the acrosome reaction

Question 17

What is the role of capacitation and hyperactivation of the spermatozoa?

Answer 17

Help detach from the tubal endothelium, leaves ‘store’ to reach oocyte

Question 18

How do sperm enter the correct fallopian tube? aka the one containing the oocyte.

Answer 18

Dominanat follice secretes progesterone
Higher levels in the ipsilateral fallopian tube
Relaxes muscles at the utero-tubal junction.
Allows controlled sperm penetration

Question 19

How do sperm find the oocyte in the Fallopian tube?

Answer 19

Specific receptors on the capacitated sperm are attracted down a chemical gradient, often by ANP or progesterone.
Sperm odorant receptors in the midpiece activated by small aldehyde molecules aid chemotaxis
Activation of adenylate kinase leads to a cAMP rise in intracellular Ca2+, attracts sperm (chemotaxis) and increases swimming speed (chemokinesis)

Question 20

What structures/processes aid the movment of the ovulated oocyte into the correct position for fertilisation?

Answer 20

Fimbriated ostium helps pick up oocyte from peritoneal cavity
Adheres to epithelium in Ft by cumulus cells
Contraction of FP smooth muscle and action of Cilia
Insterstitial cells of Cajal - regulate oviduct motility.

Question 21

How is the sperm adapted to fertilise the egg once reaching it in the fallopian tube?

Answer 21

Secretes hyaluronidases to dissolve oocyte ECM
Temporarly binds to ZP3/4 comples
Results in increases Ca2+ concentration in sperm as GCPR activated
Exocystotis of acrosome enzymes (acrosome reaction).
Acrosin, hyaluronidases and hexosaminidases aid degradation of zona pellucida.

Question 22

How does the sperm prevent polyspermy after fertilising an oocyte?

Answer 22

Fusion with the oocye membrane triggers the release of Ca2+ from the sperm
Causes a cortical reaction to reform the zona pellucida

Question 23

What events happen between the egg and the sperm immediatly after fertilisation?

Answer 23

Completion of meiosis 2 by the oocyte - triggered by increase in Ca2+
Proncuclei fusion
Formation of a zygote

Question 24

What is meant by embryonic genome activation EGA?

Answer 24

The stage in embryonic development in which the control of development is soley reliant on teh embryo genome rather than the maternal genome
This changes occurs around 72 hours post fertilisation.

Question 25

What layers does the uterus consist of?

Answer 25

• outer serosa layer
• thick layer of myometrium with spontaneous peristalitic activity
• internal endometrium consisting of a stromal matrix, simple columnar epithelium with ciliated and glandular cells

Question 26

What processes ensures the mothers body recognises and adapts to her pregnancy?

Answer 26

Trophoblast cells of the blastocyst secrete human chorioni gonadotrophin (hCG)
This prevents degradation of the corpus luteum
Binds the LH receptors on luteal cells
-stimulates secretion of progesterone and oestrogen
- essential for the first month of pregnancy before the embryo is able to self produce these hormones.

Question 27

Why is the corpus luteum important in early pregnancy?

Answer 27

Prevents the endometrium shedding
Triggers deciduation of the endometrial lining, linging becomes less ESCs and more rounded, hihgly specialised epithelioid cells.
Endometrium more receptive to implantation

Question 28

What does the blastocyst require for survival?

Answer 28

Oxygen and metabolic substrates from uterine secretions
Trophoblasts accumulate ions and organic molecules through transport mechanisms
Oxygen and carbon dioxide enter through diffusion

Question 29

What is the role of the zona pellucida after fertilisation?

Answer 29

Prevents the blastocyst from implanting in an inappropriate location in the uterus - would result in identical twins
Prevents genetically distinct conceptuses from fusing to form a chimera
Prevents cell of a pre-compaction cencptus from seperating

Question 30

What is the function of MUC-1 after fertilisation?

Answer 30

Found in the endometrium, prevent binding of embryo in an inappropriate location

Question 31

Why does the blastocyst need to hatch from the zona pellucida?

Answer 31

To allow the blastocysts to grow rapidly in size.

Question 32

What is apposition in pregnancy?

Answer 32

The differentiation of the blastocyst into two specific cell types to embryoblast and the trophoblast
The trophoblast then makes direct contact with the endometrium, this contact is unstable during apposition

Question 33

What structures aid apposition of the trophoblast to the endometrium?

Answer 33

L-selectin - allows blstocysts to role across the surface of the uterus to find a receptive area that expresses the specific oligosaccharide ligand

Leukemia-inhibiting factor (LIF) - oestrogen causes endometrial glands to produce LIF in the secretory phase of the mesntraul cycle, promotes luminal endothelial receptivity and stromal cell decidualisation (primes the uterus)

Question 34

How does adhesion of the embryo to the endometrium occur?

Answer 34

Adhesion forms a secure connection between the embryo and the endometrial lining.
Pinopodes in the endometrial lining of receptive areas - anchorage
Epidermal growth factor receptors are expressed by the trophoblast
HB-EGF bind to EFG which binds internally to EGFR in the mebryo
Signals for the foetus to upregulate adhesion molecules

Question 35

How does the embryo invade the uterus lining?

Answer 35

Adhesion causes proliferation and differentiation of the trophoblst into cytotrophoblst and syncytiotrophoblasts
STs secrete TNFalpha, reduce intracellular adhesion molecules in endometrium allows invasion
Produces lytic enzymes to invade underlying stromal cells.

Question 36

What is decidualisation during pregnancy?

Answer 36

The functional and morphological changes in the endometrium to form the decidual lining into which the blastocyst implants.
Mainly changing from stromal fibrolast cells to Decidual stromal cells.

Question 37

What ist he primary decidualisation reaction / the stromal reaction?

Answer 37

Oedema - so tissue swells
increases sprouting and growth of capillaries
Decidualisation of stroma cells.

Question 38

What is the second decidualisation reaction?

Answer 38

Endometrial component of the placenta starts to prepare

Question 39

How does the blastocyst recieves nutrients originally after implnating into the endometrium?

Answer 39

• Breakdown of degenerating decidual cells, surrounds the invading blastocysts providing nutreitns
• snycytiotrophoblast projections degrade maternal blood vessels in the endometrium, maternal blood fills lacunae and internvillus space for firect uptake from blood - start of the placenta formation

Question 40

What are the different stages in the implanatation window?

Answer 40

Day 1-7 luteal phase - prereceptive - large apical microvilli, high surface charge, thick glycolax,
Day 7-10 receptive phase - becomes receptive - pinopodes appear, loss of surface negative charge, shortening of microvilli, thining on mucin coat.
If no implanation the endometrial lining retunrs to its original properties by the refractory phase.