Oogenesis And Sexual Differentiation Flashcards

1
Q

Define sexual differentiation.

A

Sexual differentiation is the series of events whereby sexually indifferent foetuses progressively squire male or female characteristics in the gonads.

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2
Q

Describe the sexually indifferent urogenital system.

A

The sexually indifferent urogenital system consists of the metanephros (which will differentiate into the kidneys), the mesonephros and the area called the indifferent go as (the gonadal streak).

Associated with the indifferent gonad are the Müllerian duct system and the Wolffian duct system. The urogenital sinus will differentiate into the internal and external genitalia.

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3
Q

When does the very first stage of oogenesis/spermatogenesis begin?

A

Oogenesis/spermatogenesis really begins with the formation of primordial germ cells. These germ cells arise very early in foetal development (32-37 days). These cells arise at the junction between the yolk sac and the primitive hind gut. They then migrate from this region in the hind gut to the genital region/ridge. They then populate the gonads.

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4
Q

Describe the basics of sexual differentiation.

A

The basics of sexual differentiation is progression from an undifferentiated state to a differentiated state.

If the individual is XX then the Müllerian duct will progress. Of the individual is XY then the Wolffian duct will progress.

The Wolffian duct will develop into the vas deferens and the epididymis.
The Müllerian duct will develop to form the uppermost part of the uterus, the upper vagina and the oviducts.

The mechanisms for the differentiation process rely on the presence or absence of the SRY gene. The SRY gene is the testis determining factor. It maps to the P arm of the Y chromosome. It is a DNA binding protein that works by an unknown mechanism.

Hypothesis 1 is that SRY upregulates testis-specific genes such as Sox 9 which acts to upregulate anti-Müllerian hormone.

Hypothesis 2 is that SRY antagonises a gene that inhibits testicular development such as DAX-1.

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5
Q

What parts of their respective reproductive systems do the Müllerian and Wolffian ducts develop into?

A

The Wolffian duct will develop into the vas deferens and the epididymis.

The Müllerian duct will develop to form the uppermost part of the uterus, the upper vagina and the oviducts.

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6
Q

What gene does sexual differentiation rely on? How is the mechanism involving this gene thought to function?

A

The mechanisms for the differentiation process rely on the presence or absence of the SRY gene. The SRY gene is the testis determining factor. It maps to the P arm of the Y chromosome. It is a DNA binding protein that works by an unknown mechanism.

Hypothesis 1 is that SRY upregulates testis-specific genes such as Sox 9 which acts to upregulate anti-Müllerian hormone.

Hypothesis 2 is that SRY antagonises a gene that inhibits testicular development such as DAX-1.

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7
Q

Describe the determinants of sexual differentiation on the male.

A

We have a bipotential gonad, of we have the presence of SRY this may induce the production of SOX9 or DAX1. We therefore have the development of the indifferent gonad down the testis route.

The serotoli cells that develop in the testis produce Müllerian inhibiting substance (MIS), also known as anti-Müllerian hormone (AMH).

In addition the differentiating leydig cells which are steroidogenic calls on the testis produce testosterone which is responsible for the development of the internal and external genitalia.

If however the SRY factor is absent because there is no Y chromosome then we have by default the development of the Müllerian ducts and the female phenotype.

In chickens there is both a female and a male determining factor.

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8
Q

What cells in the developing testis producing anti-Müllerian hormone?

A

The serotoli cells.

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9
Q

What cells produce testosterone?

A

The Leydig cells.

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10
Q

How similar are the processes of spermatogenesis and oogenesis?

A

Spermatogenesis and oogenesis are essentially just the same process until you get down to the level of the primary spermatocytes/oocyte where the cells are still diploid.

In the case of spermatogenesis we have a situation where a primary spermatocyte gives rise to 4 spermatozoa, whereas an oocyte through its unequal replication only gives rise to one oocyte.

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11
Q

Is the ovary inactive during childhood?

A

During childhood the ovary is not inactive. At birth the ovary contains follicles at all stages of development. Unlike in rodents we do not have recruitment of a primordial follicle to a primary follicle as this occurs constantly from the third trimester of foetal development right through to puberty and adulthood.

The oocyte within the primordial follicle is arrested in prophase 1 of meiosis until either the follicle degenerates or it develops after an LH surge.

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12
Q

Briefly describe oogenesis in mice.

A

During the latter part of gestation we have the organisation of primordial germ cells into germline cysts and then in the period just after birth we have the formation of the primordial follicles and the recruitment of these follicles into the process of follicular genesis.

Formation of oocyte nests is thought to be associated with ovine ross cords of the somatic cells in mice.

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13
Q

Describe foetal ovary development in the bovine.

A

Essentially the same as human.

Have production of ovigerous cords (germ cell nests) at day 90-180. Have formation of primordial follicles from day 90 - term.

Formation of different stages of follicular genesis, primary, secondary, preantral and antral follicles occur. Antral follicles occur in the last trimester of pregnancy.

When the individual is born the ovary contains a very large number of primordial follicles, but also follicles at different stages.

Antral follicles in al, species occur at a diameter of approximately 250um. The foetal follicles are antral but are usually not so big that you would be able to see them on the surface of the ovary.

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14
Q

Describe how follicle numbers change throughout life.

A

During mid semester of foetal development you get a big increase in the number of primordial follicles up to around 7 million. After this the numbers absolutely plummet so that at birth there are somewhere between 0.5 and 2 million primordial follicles in the ovary.

There are primary follicles by 15-16 weeks gestation and Graafian follicles present at 23-24 weeks gestation.

At birth humans have about 0.5 million follicles. The number of primordial follicles declines at a pretty steady rate from the time of birth (and there is no change at around the time of puberty) until the age of 35 or 36 when the rate of loss increases quite dramatically. There are only a few hundred follicles at the time of normal menopause in the early 50s.

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15
Q

How is follicle loss controlled?

A

A large loss of follicles is due to programmed cell death as a result of FIG-alpha and Wnt-4 action.

Multi oocyte follicles is another reason why we lose quite a number of follicles. These are associated with Notch, some of the BMPs and oestrogens.

After the formation of the primary follicles we see a large loss of follicles through atresia.

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16
Q

What factors do we think are important in the transition of follicle to growing stages?

A

SCF, bFGF, BMP4, BMP7.

17
Q

What factors do we think are important for keeping follicles inactive and maintaining them as primordial follicles?

A

PTEN, FOXO3, AMH.

18
Q

What alternative view for the origin of primordial germ cells did J.L.Tilly put forward in 2005?

A

J L Tilly challenged the view that the number primordial germ cells is restricted at birth.

The idea was that their were actually progenitor stem cells contained within the bone marrow and that these stem cells could be carried through the bloodstream and be taken up by the ovary and used to repopulate and increase the number of primordial germ cells and hence the oocytes and primordial follicles within the ovary.

It now appears likely that Tilly was incorrect.

19
Q

What is the basic mechanism that we think operates to stop an individual undergoing regular menses before puberty?

A

It appears to be due to a change in negative feedback.

What happens is that oestrodiol which is produced in small amounts from the small follicles in the ovary instead of having a positive feedback effect which is what occurs during some stages of cyclic animals, oestrodiol has a negative effect on FSH and LH release acting both at the level of the pituitary and the hypothalamus.

This means that if small follicles begin to develop and they start to secrete oestrodiol this will repress the gonadotrophins and the ovaries remain inactive.

As an individual grows the degree of this negative feedback effect of oestrodiol declines, we get more gonadotrophins and this starts to build up to a situation where we have a positive feedback mechanism (LH surge).

Basically the negative feedback effects of oestrodiol on LH and FSH decreases allowing more follicular oestrogen to be produces and eventually building to an LH surge.

20
Q

We see a big increase in the weight of the uterus around puberty. What is this paralleled by?

A

An increase in the concentrations of oestrodiol, FSH and LH.

21
Q

At puberty there is an increase in nocturnal gonadotrophins. True or false?

A

True.

22
Q

What changes occur in responsiveness to sex hormones throughout childhood and puberty?

A

1) . In foetal tissue there is maturation of the negative feedback mechanism.
2) . In infancy and childhood we get:

increased release of GnRH from the hypothalamus,
we get an increase in pituitary responsiveness to GnRH,
we get rising gonadotrophin levels,
We get increased gonadal responsiveness to gonadotrophins,
We get rising sex steroid levels,
Get sleep associated increase in LH secretion and episodic secretion of LH.

3). At puberty we get less negative feedback in response to oestrodiol and activation of the positive feedback mechanism.

23
Q

What factors is the onset of puberty thought to be linked to?

A

It is likely that the onset of puberty is linked to size and nutritional factors.

It is thought that this link between body size and the onset of puberty is due to a factor called Leptin. Leptin is secreted by the fat.

24
Q

Leptin has now been supplanted by two factors that it is thought are much more likely to cause the onset of puberty. What are these factors?

A

1) . GPR54 - G-protein coupled receptor. GPR54 knockout mice fail to undergo puberty, are sterile and have small genitalia. Human mutants have hypogonadotrophic hypogonadism.
2) . KISS-1 / metastatin - ligand of GPR54. Encodes a 145 amino acid protein which is then processed to a 54 aa biologically active protein called metastatin. Can stimulate LH and FSH secretion.

GPR54 Knockouts have small gonads, low steroid and gonadotrophic levels.

GPR54 and KISS-1 are very important in seasonal breeding, possible link to nocturnal gonadotrophin levels.

25
Q

Define oogenesis.

A

The process of egg formation that begins in the embryo and continues in the adult.