Reproduction and Embryology

Question 1

What are the advantages of sex?

Answer 1

Each individual has a new mix of genes that give it immunity to pathogens (the Red Queen syndrome) and each individual has a new mix of genes that determine its environmental interactions.

Question 2

What is the germ line?

Answer 2

Very early in embryonic development, a set of cells is set aside to become the ‘germ line’. These go on to form the gametes.

Question 3

What is Spermatogenesis?

Answer 3

Proliferation of germ line stem cells by mitosis, reduction to haploid state by meiosis, differentiation into mature spermatozoa.

Question 4

Describe the mitotic proliferation of sperm.

Answer 4

Begins at puberty, produces around 10,000 sperm per second - 10^8 sperm/ml semen.
Daughters of spermatogonium (2N) division are cross-linked with cytoplasmic bridges to share metabolism.

Takes place in basal side of tubule (furthest from lumen).

Question 5

Describe the process of spermatogenesis.

Answer 5

Spermatogenia cells (stem cells on the basal layer) differentiate by mitosis to replace their number as some of them leave the basal layer and move up away from it and undergo meiosis.

Just before meiosis I, the two copies of each chromosomes come together and swap segments. So after meiosis II, get 4 unique daughter cells.
As the daughters are undergoing division, they have cytoplasmic bridges which cross-link them to share metabolism for efficiency.

Sertoli cells act as nursing cells for them. Do their metabolism since the spermatozoa don’t have lots of organelles, instead embedded in the sertoli cells.

Question 6

What are the hormonal inputs for spermatogenesis?

Answer 6

Petuitary secretes FSH and LH which talk to the somatic cells in the testes.

LH makes Leydig’s cells make testosterone, which stimulates Sertoli cells and rest of body.
FSH also stimulates Sertoli cells, which stimulates spermatogenesis and releases inhibin.

Inhibin and testosterone act as feedback to reduce production of FSH and LH. In male steady level of FSH and LH because of this.

Question 7

Describe the maturation of sperm.

Answer 7

Shed from the Seroli cells and flow to the epididymis, which alters seminal fluid. Epididymal secretion (glycoproteins…) activate sperm to make them capable of swimming.

Question 8

Describe the process of Oogenesis.

Answer 8

Adult women have no germ line stem cells.

In foetus, mitosis to bulk up numbers and then they begin to enter meiosis.

Meiosis is paused for 12-50 years (in childhood) and then completes at some point between menarche (first period) to menopause.

Makes about 13 gametes a year.

Question 9

What is oogenesis?

Answer 9

Process of making the female gamete.

Question 10

What is the primordial follicle?

Answer 10

What the oocyte that has been arrested in meiosis I lies in.

The oocyte is surrounded by a thin layer of granulosa cells that protect it.

A few primordial follicles a day commence further development (after puberty).

Question 11

What is the primary follicle?

Answer 11

From the primordial follicle - a few a day commence into this stage which lasts about 85 days.

Oocyte becomes bigger (synthesises more rRNA and mRNA but doesn’t progress further through meiosis).

Granulosa cells become thick but still a single layer.

Question 12

What is the ripening follicle?

Answer 12

Phase of about 10 days after the primary follicle phase.

The oocyte synthesises a glycoprotein zona pellucida.

Granulosa cells multiply and several cells thick. Then they secrete follicular fluid, forming fluid-filled ‘antrum’.
Theca forms around the whole thing which gains LH receptors. Granulosa gains FSH receptors.
Together theca and granulosa activate hormone secretion from the follicle.

Question 13

What hormones influence oogenesis?

Answer 13

LH - receptors on the Theca
FSH - receptors on the Granulosa

Theca under influence of LH makes androgens (like testosterone) locally which the FSH turns (aromatizes) into oestrogen. This activates hormone secretion from the follicle.

Follicle needs these hormone peeks to be adequate or it will die. So only surviving follicles are the ones that are at the right stage of the menstrual cycle where FSH is high enough.

There is feedback by oestrogen but it causes overshoot and oscillation which leads to the menstrual cycle.

When a follicle survives it releases oestrogen which feeds back to the pituitary, reducing LH and FSH levels, preventing other follicles from surviving.

Question 14

What is the maturing follicle?

Answer 14

Antrum fills up with even more fluid until it explodes and oocyte released out through the ovary. This happens during the big peak of the LH hormone. Only completes meiosis II if fertilised.

Remains of ruptured follicle become the Corpus Luteum which produces hormones (progesterone, oestrogen) that prepares lining of uterus to receive embryo. It will die after a week unless women is pregnant.

Question 15

What is capacitation?

Answer 15

Happens in female reproductive tract to make sperm able to fertilise egg.

Glycoprotein and sterol coat acquired in epididymis is removed by proteases in unterine/cervical/vaginal fluid.
Causes sperm cell membrane to be more permeable to calcium ions. Ca is a second messenger that activates the sperm.
Indirectly via cAMP activates strong tail lashing, and makes acromosome reaction possible later.

Question 16

What happens when the sperm meet the Zona Pellucida?

Answer 16

Zona pellucida is jelly-like layer around the oocyte.

Sperm recognises it and undergoes an acrosome reaction - golgi aparatus (which has become the axon) fuses with the outside membrane of the cell so contents of the axon can flow around the cell and digest the ZP.

Question 17

What happens once the sperm fuse with the oocyte membrane?

Answer 17

Contents of the sperm can now flow into oocyte - only nucleus important.
This causes waves of cytoplasmic calcium in the oocyte, which has two effects;
First cortical granules are released which alter the Zona pellucida to make impenetrable/non-digestable by sperm and block further fusion.
Secondly it triggers resumption of meiosis.

One nucleus inherits all of the oocyte and the other is squeezed out as waste.

Question 18

What happens at the cleavage stage of embryonic development?

Answer 18

Goes from one cell to around 8. Mitosis occurs but there’s no growth - the cells get smaller each time it divides. Doesn’t need food/resources.

Question 19

What happens at the 4 cell stage of embryonic development?

Answer 19

mRNA begins to synthesise from embryo’s own DNA by switching on it’s own genome.
Before this it was running off of leftover mRNAs from mother, but they are now destroyed.

Question 20

How does the embryo make cells of different types?

Answer 20

Once you get to a morella (ball of cells of 16-32), inside cells are completely surrounded by outside cells, whereas outside cells have a free surface.

The cells on the outside will become specialised epithelial cells - trophectoderm.
Starts to pump fluid inside - where the inner cell mass (blastocyst) has formed from the cells that have no free surface.

Trophectoderm will become placenta and other extra-embryonic material. Inner cell mass will become body and some extra-embryonic membranes.

Question 21

What happens after traphectoderm and inner cell mass form?

Answer 21

Traphectoderm starts to make human chorionic gonadotropin (hCG) which prevents menstrual cycle and acts similarly to LH to maintain uterine epithelium.

Embryo hatches through zona pallucida then travels down fallopian tube, where it implants.

Trophoblast develops into placenta.

Question 22

How is the yolk sac formed?

Answer 22

After the trophoblast has formed and there is a bunch of inner cell mass (ICM) at one edge and fluid surrounding it, the cells in the ICM that have a free surface (are fluid-facing) differentiate and become the hypoblast, which also goes around the inside of the trophoblast, lining it and forming the yolk sac.

Question 23

How is the amniotic cavity formed?

Answer 23

The layer of cells touching the hypoblast directly let go of the cells above them but cling onto the hypoblast, forming a second layer - the epiblast. This creates the amniotic cavity.

Question 24

Describe axis formation in an embryo.

Answer 24

Cells at the centre of the hypoblast make ‘Hex’.
The cells that express hex move out to the rim and congregate at one point.
These cells secrete proteins that inhibit progress in the epiblast layer above.
Only the cells at the far point from the Hex-expressing cells escape inhibition.
These cells begin making the tail end of the primitive streak.

Question 25

What are the three forms of monozygotic twinning?

Answer 25

1. The cells seperate inside the zona pellucida - have seperate membranes, yolk sac, placenta - safest
2. Two inner cell masses form - share a placenta but separate amniotic sac - danger of foetal transfusion syndrome
3. Two primitive streaks form (very rare) - share everything - danger of becoming conjoined

(4. Partial axis duplication - two head ends of the primitive streak but only one tail end)

Question 26

What is gastrulation?

Answer 26

The making of a 3-layered structure from the flat disc of an epiblast.
Ectoderm (outer skin), mesoderm (middle layer of muscle etc.), and endoderm (inner skin - gut)

Question 27

Describe the process of gastrulation.

Answer 27

Epiblast cells stream in towards the middle and then dive down towards hypoblast.

The first cells that dive down go all the way to the hypoblast and shuffle the hypoblast cells aside to eventually replace them. This forms the endoderm (gut lining).

The second batch of cells make a middle layer of loosely packed cells, not closely associated with each other, but that do have a matrix. This forms the mesoderm (middle layer).

The third lot of cells never dive through and remain in the layer that becomes the ectoderm.

A middle part of the endoderm buds off and becomes the notochord.

Question 28

How does the gut tube form once we have endoderm, mesoderm and ectoderm?

Answer 28

As the embryo grows along it’s cranial and caudial axis (our long axis), the opening for the yolk sac does not grow.

This means that the very ends of the endoderm are basically pinned in place. So as it gets longer, it has to kink and get pulled out, creating a tube.

Question 29

What is neurulation?

Answer 29

The formation of the CNS from the ectoderm.

Question 30

Describe the process of neurulation.

Answer 30

Ectoderm over the back folds inwards, driven by local cell shape changes along three stripes (2 edge stripes and one centre stripe).

The cells from the edge stripes become wedge-shaped with a narrow base, and the cells from the centre stripe become wedge-shaped with a narrow apex, this creates a valley shape, with the inside stripe folding.

Cell proliferation causes an inward push, bringing the edges together, eventually leading to sealed ectoderm and a neural tube. The cells in both of these are different and distinct.

Question 31

Describe the control of body size.

Answer 31

The pituitary gland releases growth hormone.
Most tissues don’t respond directly to GH but some do (mainly muscle), and they relay the signal in the form of IGF1 and IGF2 (insulin-like growth factors).

Question 32

What is Laron syndrome?

Answer 32

People who can’t make growth hormones, or more commonly, can’t make receptors for it. But they are in normal proportion.

Question 33

How does limb length stay in proportion?

Answer 33

General signals are from IGF-1.

Internal signals from dying cartilage cells that matured from the growth plate to form bone.
They signal to the stem cells in the zone of proliferation to make more cells to replace them by sending IHH into the sheath (periosteum) of the bone. This causes the periosteum to release PTHrP which tells the cells in the growth plate to proliferate.

When the bone is small the signal from the periosteum to the growth plate and back only needs to travel a short distance and so is very effective.
At the bone grows, the distance between the periosteum and the growth plate increases, as it does so the signal becomes increasingly inefficient as it gets more diluted.
Eventually so inefficient it stops working.

Question 34

What is phocomelia?

Answer 34

Babies born with smaller limbs - like from Thalidomide because it slows blood vessel growth, killing developing blood vessels and growth is a very vascular process.

Question 35

What is achondroplasia?

Answer 35

Genetic condition meaning cartilage in limbs fail to grow due to mutation in FGFR3. This usually inhibits proliferation and differentiation of chondrocytes. Mutated version sends signal ligand is bound all the time so growth plate is full of chondrocytes and grwoth plates close prematurely.

Question 36

Describe the development of germ line cells in the gonads.

Answer 36

Develop in trunk of body, about half way between shoulder and pelvis, at the gonadal ridge. They eventually move to pelvis in females and scrotum in males.

Before gastrulation, germ line removed from the inner cell mass and end up in the yolk sac.

When ready, germ line cells wander up mesentery (gut tube) until they reach the gonadal ridge where the cross the mesentery and move across to invade the developing gonads.

Question 37

What determines sex?

Answer 37

The SRY gene on the Y chromosome (only found in males).

Question 38

How does SRY act?

Answer 38

Primitive gonads consist of somatic cells and germ line cells. Somatic cells express SRY (if presesnt).

This forces somatic cells to develop into testis cells - otherwise they form overy cells (which is the path they would take without SRY intervention).

Question 39

How is sex determined outside the gonads?

Answer 39

Rest of the body doesn’t pay attention to whether it has a Y chromosome or not. Testis communicates with the rest of the body by excreting androgenic hormones (testosterone and AMH) to follow the male pathway, otherwise the female pathway will happen.

Question 40

What happens in Complete Androgen Insensitivity?

Answer 40

The person has XY chromosome and develops internal testis but as androgen receptors don’t work, has a typically female looking body and external genitalia.

Question 41

What happens in 5a-reductase deficiency?

Answer 41

Known as ‘guevedoces’

Testosterone (weakly stimulates androgen receptor) can’t be converted into 5a-dihydrotestosterone (stimulates androgen receptors strongly).

This means XY chromosome but children with it make female bodies.

In puberty, testosterone levels are high enough to act as an androgen even without 5a-reductase so body changes into male (including external genitalia).

Question 42

What is 5a-reductase?

Answer 42

Testosterone (produces in testes) only stimulates androgen receptors weakly. In the tissues 5a-reductase converts it to 5a-dihydrotestosterone which stimulates androgen receptors strongly.