Fertilisation and Luteal Phase

Question 1

What is sperm like when it enters the cervix?

Answer 1

Sperm passes into cervix:

- Cervical mucus is less viscous in the absence of progesterone allowing sperm to pass.
- Sperm can inhabit cervical crypts which may form a reservoir for slow release of the sperm. 
- Some evidence of thermotaxis, but mechanism not yet elucidated.
- Fertilisation is typically within 24-48 hours but sperm has been recovered alive after 5 days.

Question 2

What is the sperm’s journey to the egg like?

Answer 2

Passage through uterus not well understood, currents set up by uterine or tubal cilia may have a role.
Chemo-attractants released from the oocyte cumulus complex may attract the sperm.
Sperm become hyperactivated.
Forceful tail beats with increased frequency and amplitude mediated by Ca2+ influx via CatSper channels.

Question 3

What happens to sperm before and during fertilisation of the egg? (Capacitation and acrosome reaction)

Answer 3

Freshly ejaculated sperm cannot fertilise an egg.
Capacitation needs to happen first so the acrosome reaction can happen
Capacitation is partly achieved by removing the sperm from the seminal fluid, also uterine or tubal fluid may contain factors which promote capacitation.
Biochemical rearrangement of the surface glycoprotein and changes in membrane composition must occur before the acrosome reaction can occur.
Capacitation takes between 4 and 18 hours as it allows the sperm to get in the region of the egg, so that it doesn’t just hit a uterine wall and explode.
Acrosome reaction occurs in contact with the zona –cumulus complex; the acrosomal membrane on the sperm head fuses releasing enzymes that cut through the complex.
Acrosin bound to the inner acrosomal membrane digests the zona pellucida so the sperm can enter.

Question 4

Give a brief overview of ovulation

Answer 4

The LH spike causes resumption of meiosis and ovulation.
Converts the primary oocyte to secondary oocyte plus 1st polar body.
Basement membrane breaks so blood pours into the middle.
An inflammatory cascade from the LH spike causing the little drop of liquid to be exuded along with the egg
Oocyte cumulus complex extruded out and caught by fimbrae of uterine tube.
Theca and granulosa become mixed and the empty follicle is known as the corpus luteum.
It produces progesterone in the luteal phase.

Question 5

What do progesterone and oestrogen do in the luteal/secretory phase?

Answer 5

Progesterone:
- Makes the endometrium secretory and receptive to implantation.
- Supresses cilia in uterine tubes once oocyte has already passed.
- Makes cervical mucus viscous again to prevent further sperm penetration.
Oestrogen:
- Helps to maintain endometrium in luteal phase (causes proliferation in follicular phase).

Question 6

What happens to the corpus luteum if fertilisation does not occur?

Answer 6

If fertilisation does not occur, CL has an inbuilt finite lifespan of 14 days.
Regression of CL essential to initiate new cycle.
Fall in CL-derived steroids causes inter-cycle rise in FSH.
Cell death occurs, vasculature breakdown, CL shrinks. Over time it becomes a corpus albicans.
CL rescued in pregnancy by hCG from embryo binding to its LH receptors.
CL continues to produce progesterone and maintain endometrium.
The only difference between LH and hCG is their beta chain, they have the same alpha chains

Question 7

Give a brief description of the structures in an oocyte at ovulation?

Answer 7

Cumulus oophorus- these are the granulosa cells essentially and they protect the egg
The innermost layer of the cumulus are the corona radiata, these are the granulosa cells with the most contact to the zona pellucida
Formed by granulosa cells adhering to the oocyte before it leaves the ovarian follicle
Zona pellucida is secreted by the egg
This has changes that occur in it that become impenetrable after fertilisation
The 1st polar body is the result of the 1st meiotic division
Cortical granules are involved in the Zona Pellucida impenetrable reaction that contains lots of enzymes
Between the plasma membrane and the ZP there is a little space called the perivitelline space
This is also involved in the cortical reaction of the ZP becoming impenetrable to other sperm

Question 8

How does the sperm bind to and penetrate the egg?

Answer 8

1. The acrosome reaction occurs in contact with the zona-cumulus complex.
   Sperm penetrate cumulus and the internal acrosomal membrane’s adhesion molecules bind to ZP.
2. Sperm enzymes cut through ZP and sperm fuses with plasma membrane.
3. Sperm taken in by phagocytosis.
   Phospholipase Zeta (similar to phospholipase C) in the sperm activated by basal Ca2+ inside egg. PIP2 → DAG + IP3
   Causes release of intracellular Ca2+ leading to large Ca2+ spike.
4. Cortical reaction as wave of Ca2+ sweeps around egg causes the release of proteases, peroxides and hyaline prevents polyspermy by making the ZP impenetrable

Question 9

What is syngamy?

Answer 9

After meiosis I the oocyte has 23X chromosomes, but 2 copies of each chromosome arranged as sister chromatids.
Entry of the sperm causes an increase in Ca2+ via phospholipase Zeta from sperm.
Ca2+ causes the completion of meiosis II expelling the second polar body & cortical reaction.
The sperm nuclear membrane breaks down, the chromatin decondenses and chromosomes separate.
4-7 hours after sperm penetration the two sets of haploid chromosomes become surrounded by distinct membranes forming two haploid pronuclei.
These haploid structures synthesise DNA in preparation for the first mitotic division.
The pronuclei fuse and the mitotic metaphase spindle forms with the chromosomes assuming their position at its equator.
Mitosis is completed and the one cell zygote becomes a two cell embryo.

Question 10

What does early embryo development entail?

Answer 10

The fertilized egg has 2 pronuclei.
This is the first sign of fertilization.
The developing embryo contains 6-8 cells 3 days after fertilization
Five days after fertilization it is called a blastocyst and differentiates into inner cell mass, blastocoel and trophoblast.