Coitus, fertilisation & preimplantation

Question 1

Identify the main phases of human sexual response.

Answer 1

4 phases - EPOR model

1) Excitement sexual arousal: psychological and physical stimulation of erogenous zones. Tumesence and erection of penis and clitoris, engorgement of female tract
• Parasympathetic -erection
• Sympathetic -ejaculation

2) Plateau intensification of arousal
3) Orgasm series of involuntary muscular contractions in both sexes with intense pleasurable sensations
4) Resolution detumescence and time during which re-arousal is impossible (may not be true of women)

Question 2

Which of the uterine/ovarian cycles is fixed ? Which is variable ? How does this affect day of ovulation, and the length of the entire cycle ?

Answer 2

• Length of the luteal phase is fixed at approximately 14 days (pretty much regardless of length of total cycle)
• Follicular phase varies
• Menstrual phase varies

This means that the whole cycle is variable, may be 25, 28, 35 days etc. The day of ovulation also changes (e.g. may be on day 11, 14, 21).

Question 3

How long are sperm viable for ? Oocytes ? How does this affect fertilisation ?

Answer 3

• Sperm are viable for 24 – 72 hours
• Oocytes are viable for 12 – 24 hours
For fertilisation to occur, coitus must occur no more than 3 days before ovulation (since sperm can survive 3 days) and no more than 1 day after (since occytes can survive one day).

Other guidelines say:
• Sperm are viable for 4-6 days
• Oocytes are viable for 24-48 hours
so for fertilisation to occur, sperm introduction should be between 5 days before and one day after ovulation.

Question 4

Is control of development of the fetus maternal, or fetal ?

Answer 4

Initially, maternal. After fertilisation, control of development will switch from maternal to foetal (the embryo must communicate with the mother to convert her whole physiology from a cyclic state to a pregnant one)

Question 5

State the trimesters of pregnancy.

Answer 5

• First Trimester weeks 1 -12
• Second Trimester weeks 13 – 28
• Third Trimester weeks 29 – 40

Question 6

At which stage of pregnancy do most miscarriages occur ?

Answer 6

• First Trimester weeks 1 -12, most miscarriages occur

Question 7

At 24 weeks, what is the survival rate for early prematurity ?

Answer 7

• At 24 weeks 50% survival rate for early prematurity.

Question 8

When does parturition typically occur ?

Answer 8

Parturition at about 40 weeks from LMP

Question 9

What proportion of all pregnancies miscarry ?

Answer 9

10-15 % of all pregnancies miscarry

Question 10

For couple:
– using no contraception
– trained to detect 6 most fertile days around ovulation

How many will be pregnant after two cycles ? How many will be pregnant by 6 months ? How many will be pregnant after 1 year ? How many will be subfertile ?

Answer 10

For couple:
– using no contraception
– trained to detect 6 most fertile days around ovulation

• 50% pregnant after 2 cycles
• 85% pregnant after 6 months
• Half the remaining couples were pregnant after 1 year
• Leaves ~5 % subfertile

Question 11

What proportion of unprotected intercourse results in development to the blastocyst stage ? What about IVF ?

Answer 11

Only 20 % of unprotected intercourse results in development to the blastocyst stage (Similar success rate for IVF)

Question 12

What are causes of failure of unprotected intercourse in resulting in a normal birth ?

Answer 12

• Pre-implantation and post-implantation failure occurs frequently - spontaneous abortion
• Blastocysts fail to implant

Question 13

What proportion of blastocysts will fail to implant ?

Answer 13

• 8-20% of blastocysts fail to implant

Question 14

What proportion of clinically detected pregnancies will fail in the first 12 weeks (ie in 1st trimester) ?

Answer 14

Clinically detected pregnancies 15 – 20 % will fail in the first 12 weeks (ie in 1st trimester)

Question 15

What proportion of human conceptions survive to successful birth ?

Answer 15

• Possible that less that 15 – 20% of human conceptions survive to successful birth

Question 16

Define embryonic period.

Answer 16

• Embryonic period – 8 weeks (1 to 8)

• Preimplantation embryo (fertilised developing embryo which has not implanted yet)
• Implantation
• Differentiation and development of the organ systems

Question 17

Define feteal period.

Answer 17

• Foetal period 8 – 40 weeks

• Differentiation continues
• Growth

Question 18

What is the clinical significance of the embryonic period ?

Answer 18

Mother may not know that she is pregnant during this sensitive period.
– She may not avoid harmful influences that may affect the development of the embryo (alcohol, tobacco, prescription drugs).

Question 19

Describe the events of the ovum immediately following ovulation.

Answer 19

At ovulation:
• Egg extruded onto surface of ovary.
• Smooth muscle of fimbriae cause them to pass over ovary while cilia beat in waves toward interior of Fallopian tube.

Question 20

Describe the physiological events occurring following ejaculation in coitus.

Answer 20

• Ejaculation deposits semen into vagina then move down into cervix.
• Passage into cervical mucus dependent on oestrogen-induced changes in mucus consistency (to allow sperm to move through it)
• Sperm can reach uterus minutes/hours after ejaculation.
– But can survive 1-2 days within cervical mucus before release to enter uterus.
• Movement through uterus and fallopian tubes is via sperm’s own propulsions (activity of tail) AND smooth muscle uterine contractions.

Question 21

How many sperm die from the vagina to the Fallopian tubes ? Why ?

Answer 21

• Sperm mortality from vagina to fallopian tubes is large.
– Several hundred million to 100-200 (reason for large number of sperm in ejaculate)

Because:
• Vaginal environment is acidic.
• Length and energy requirements of trip.

Question 22

Define capacitation.

Answer 22

the process in which the spermatozoon, after it reaches the ampulla of the fallopian tube, undergoes a series of changes that lead to its ability to fertilize an ovum.

Question 23

Describe the process of capacitation.

Answer 23

• Action of female tract secretions on sperm over several (6-8) hours.
– Essential for them to be capable of fertilisation

• Causes:
– Change from wavelike beats of sperm tail to whip-like action to propel sperm forward.
– Sperm’s plasma membrane is altered so it is capable of fusing with surface membrane of egg (acrosome reaction).

• Capacitation destabilises the sperm surface membrane to enhance fusion with oocyte

• Increase in Ca2+ permeability - rise in intracellular Ca2+
• Removal of membrane proteins (glycoprotein)
• Change in surface charge
• Depletion of cholesterol

Question 24

Where does fertilisation usually occur ?

Answer 24

• Normally occurs in ampulla of the uterine tube.

Question 25

When does fertilisation begin ?

Answer 25

• Begins with fusion of sperm and egg

– Usually a few hours after ovulation and within 24-48h of ovulation.

Question 26

Describe the process of fertilisation.

Answer 26

1) Sperm cell weaves past follicular cells and binds to zona pellucida.
2) A rise in (Ca++)i inside the sperm cell triggers the exocytosis of the acrosome (acrosomal reaction) which contains hydrolytic enzymes (many sperm cells undergo acrosome reaction)
3) Hydrolytic enzymes contained in the acrosomal cap are released. These enzymes locally dissolve the zona pellucida. The whip-like action of the tail pushes the sperm head towards the oocyte membrane (only one sperm moves through zona pellucida).
4) With the head of the sperm now lying sideways, microvili on the oocyte surround the sperm head. The two membranes fuse. The contents of the sperm cell enter the oocyte; the sperm-cell membrane remains behind.
5) A rise in (Ca++)i inside the oocyte triggers the cortical reaction, in which there is exocytosis of granules that previously lay immediately beneath the plasma membrane. The enzymes released lead to changes in the zona pellucida proteins, causing the zona pellucida to harden, preventing the entry of other sperm cells.
6) The rise in (Ca++)i inside the oocyte induces the completion of of the oocyte’s second meiotic division and the formation of the second polar body, which usually lies next to the first polar body.
7) The head of the sperm enlarges to become the male pronucleus.
8) Male and female pronuclei fuse.
9) Zygote begins embryogenesis

Question 27

How is the acrosome reaction triggered ?

Answer 27

Induced by the sperm head contacting the zona pellucida and binding to glycoproteins ZP2 and ZP3

Question 28

Describe the acrosome reaction.

Answer 28

• Fusion of the acrosome plasma membranes
• Releases contents of the acrosome
• Causes entry of more Ca++ (further increases intracellular concentration)

• Sperm then digests a path through the zona pellucida (proteolytic enzymes)

Question 29

Identify the main events in the Ovulation – fertilisation - implantation chain. Also identify the number of day after LH peak after which they occur, and their location.

Answer 29

♦ Ovulation (1 day after LH peak), in ovaries
♦ Fertilisation (2 days after LH peak), in Fallopian tube
♦ Cell division to 32 cells (2-4 days after LH peak), in Fallopian tube
♦ Blastocyst enters uterine cavity (5 days after LH peak), in uterus
♦ Implantation (6-7 days after LH peak), in uterus
♦ Human chorionic gonadotropin (hCG) from implanted blastocyst (trophoblast cells) rescues corpus luteum (9-10 days after LH peak), in trophoblast -> maternal ovary

Question 30

Describe the process of cell division to 32 cells.

Answer 30

• Conceptus (the product of the union of oocyte and spermatozoon at any stage of development from fertilization until birth) “held” in fallopian tube as oestrogen maintains contraction of smooth muscle near where fallopian tube enters wall of uterus.
• Conceptus undergoes a number of mitotic cell divisions ie cleavage into 2, then 4, then 8-cell stage. Then morula is formed (i.e. 16-32 cell stage, at around 72 hours).
– Divisions are unusual as no cell growth occurs before each division, therefore the conceptus reaching uterus is same size as original fertilised egg.
• Cells are totipotent.

Question 31

Distinguish between the different possible potency level of cells.

Answer 31

• Totipotent cells can form all the cell types in a body, plus the extraembryonic, or placental, cells. Embryonic cells within the first couple of cell divisions after fertilisation are the only cells that are totipotent.
• Pluripotent cells can give rise to all of the cell types that make up the body; embryonic stem cells are considered pluripotent. Blastocyst also pluripotent.
• Multipotent cells can develop into more than one cell type, but are more limited than pluripotent cells; adult stem cells and cord blood stem cells are considered multipotent.

Question 32

Which stage of development can we use for genetic testing ? Why ?

Answer 32

Blastocyst is pluripotent (not totipotent) so a cell can be removed for testing without damage to the embryo (remaining cells can still go on and form all the required tissues)

Question 33

Describe the process of blastocyst/conceptus entering the uterine cavity.

Answer 33

• Plasma progesterone levels rise 3-4 days after fertilisation, smooth muscle relaxes and conceptus passes into uterus.
• Approximately 4-5 days after fertilisation, cavities develop between the cells.
• For approx 3 days, conceptus/blastocyst lies free in the uterine cavity supported by uterine secretions, receiving nutrients from it.

Question 34

Describe the structure of the blastocyst.

Answer 34

Trophoblast: will give rise to the placenta

Inner cell mass: will form the embryo

Question 35

Describe the process of implantation.

Answer 35

• Day 6 the blastocyst attaches to the endometrium adjacent to the inner cell mass (embryonic pole)
• Trophoblast differentiates into:
- inner cytotrophoblast
- outer syncytiotrophoblast (loses cell boundaries)
• Fingers of syncytiotrophoblast invade the endometrium (and ultimately will help the placenta develop)