Urology - Hormonal control of testicular function Flashcards

1
Q

When does spermatogenesis start?

A

Spermatogenesis is the production of male gametes, or spermatozoa. It occurs in the testes around the onset of puberty. In males, testosterone production and spermatogenesis occur continuosly.

These 2 processes are controlled by the posterior pituitary glycoprotein gonadotrophins, follicle stimulating hormone (FSH) and leutinising hormone (LH).

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2
Q

When should the testes descend? If they fail to do so why does this cause infertility?

A

The testes should descend a few weeks before birth. They pass out of the abdominal cavity and into the scrotal sac. Failure of the testes to descend is called cryptorchidism. It causes infertility because spermatogenesis is disrupted, as it depends on a temperature of about 4 degrees below body temperature.

This lower temperature is maintained by a counter current heat exchange between the testicular artery and the papiniform plexus of veins that are filled with blood at a lower temperature.

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3
Q

Where in the testes does spermatogenesis take place?

A

Spermatozoa are the male gametes and these are produced (by the process of speramtogenesis) in the seminiferous tubules. These tubules are lined with germ cells and Sertoli cells. The Sertoli cells surround the developing germ cells and provide them with nutrients and stimulating factors (they are sometimes referred to as “nurse cells”). They also secrete a number of hormones such as androgen binding protein and inhibin.

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4
Q

What triggers spermatogenesis?

A

At puberty, GnRH secretion from the hypothalamus becomes pulsatile and stimulates gonadotrophin (LH and FSH) release from the anterior pituitary. These hormones initiate spermatogenesis which occurs continuously thereafter.

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5
Q

What cells are spermatozoa produced from?

A

Primordial germ cells that enter the foetal testes divide and become spermatogonia - the stem cells of the testes that divide by mitosis and meiosis. There are 3 phases of spermatogenesis:

1) proliferation
2) division
3) differentiation

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6
Q

What happens during the proliferation phase of spermatogenesis?

A

This happens during puberty. Primordial germ cells are reactivated and undergo mitosis in the basal compartment of the tubule.

They form As spermatogonia (spermatogonial stem cells) which are a reservoir of self renewing stem cells. These go on to form A spermatogonia which are the start of spermatogenesis.

Each A spermatogonium undergoes mitosis to form type B spermatogonium which divide again to form primary spermatocytes.

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7
Q

What happens during the division phase of spermatogenesis?

A

This is where primary spermatocytes undergo a meiotic division. Primary spermatocytes move into the adluminal compartment by passing through the blood testes barrier (BTB). They undergo a first meiotic division to form 2 secondary spermatocytes, and these in turn undergo a second meiotic division to form haploid round spermatids.

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8
Q

Spermiogenesis

A

This is another term for the third phase of spermatogenesis or differentiation. Round spermatids elongate to form elongated spermatids and finally mature spermatozoa.

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9
Q

How long does spermatogenesis take?

A

Approximately 70 days.

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10
Q

Are spermatozoa capable of fertilising an ovum straight away?

A

No. When spermatozoa are released into the seminiferous tubule they are non-motile and incapable of fertilising an ovum. From the seminiferous tubule, spermatozoa pass into the epididymis where they mature and are stored until ejaculation.

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11
Q

What happens to sperm that are not ejaculated?

A

The production of spermatozoa is continuous. Spermatozoa that are not ejaculated sometimes pass into the urine (spermaturia) or eventually deterioate and are reabsorbed within the epididymis.

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12
Q

Describe the features of a mature sperm

A

Mature sperm consist of a head, middle peice, principal piece and end piece. The head is composed mainly of the nucleus and is covered by a cap known as the acrosome. This is a large vesicular structure containing lytic enzymes that help penetrate the zona pellucida of the ovum. The middle piece consists of a helical sheath of mitochondria surrounding a core of contractile microtubules called axoneme. This extends to the tail.

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13
Q

What is the blood testes barrier (BTB)?

A

The BTB is located between the basal and adluminal compartments of the seminiferous tubule. Adherens and gap junctions link adjacent Sertoli cells to each other to form the BTB. It develops during puberty prior to the onset of spermatogenesis.

It has 2 functions:

1) separates sperm from the immune system preventing an immune response
2) selective transport of ions and small molecules

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14
Q

What is capacitation?

A

Capaciation is not to be confused with sperm maturation that occurs in the epididymis. Capacitation is a physiological change that sperm undergo before they can penetrate the female egg. It involves hyperactivation of the tail and the acrosome reaction in the head. It occurs in the female tract.

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15
Q

What type of hormone is testosterone?

A

Testosterone is the principal androgenic hormone produced by the testes. It is a C19 steroid hornome synthesized from cholesterol. It is secreted by the interstitial cells of Leydig which are found between the seminiferous tubules. Most of the androgens are synthesised here, but a small amount is also produced by the adrenal cortex.

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16
Q

How is testosterone transported in the blood?

A

Once relased into the circulation, testosterone is bound to a binding protein called sex hormone binding globulin. In most of its target tissues (except muscle) testosterone is converted into a more potent andorgen called dihydrotestosterone by the enzyme 5 alpha reductase.

17
Q

How does testosterone produce its physiological effects?

A

Both testosterone and dihydrotestosterone act via nuclear receptors to promote gene activation by diffusing across the cell membrane.

18
Q

Metabolism of testosterone

A

It is metabolised in the liver by reduction and conjugation with glucuronic acid and the metabolites are then excreted by the kidneys.

19
Q

What are the effects of testosterone?

A

Testosterone prootes the development of the male reproductive system and of secondary sexual characteristics - i.e. enlargement of the penis and testes, increased rate of growth of muscle and bone, appearance of facial, axillary and body hair etc.

20
Q

How do LH and FSH control spermatogenesis?

A

FSH controls spermatogenesis, whilst LH controls the synthesis of testosterone. LH binds to LHCG receptor on interstitial Leydig cells and induces them to produce testosterone which moves into the tubules and binds to the androgen receptor on Sertoli cells.

FSH binds to the FSH receptor on Sertoli cells and induces the expression of the androgen receptor (that testosterone binds to) and also stimulates androgen binding protein (binds testosterone and maintains high intraluminal concentration).

Both LH and FSH act through cAMP.
Both FSH and testosterone are required for normal spermatogenesis.

21
Q

Describe negative feedback in the HPG axis in males?

A

Testosterone inhibits secretion of LH via negative feedback, but also acts on the hypothalamus to reduce GnRH release). It has less of an effect on FSH.

Inhibins are glycoprotein hormones secreted by Sertoli cells in the tests and have a negative feedback effect on secretion of FSH.

22
Q

What is found in semen?

A

Semen contains spermatozoa and secretions from the seminal vesicles, prostate gland and blubourethral glands. The average volume of ejaculate is about 3ml which tonains 100 million spermatozoa.

Secretions from the accessory glands comprise about 95% of semen volume. There is high concentrations of fructose (energy source) and prostaglandins (aid motility in the uterus).

23
Q

What are the phases of penile erection?

A

Erection is caused by engorgement of the penis with blood. This occurs in several stages.
1) Flacid phase - low arterial and venous blood flow

2) Filling phase - arterial smooth muscle relaxation leads to rapid increase in penile blood flow, while venous drainage remains constant. Volume of the penis increases.
3) Tumescence phase - after reaching a submaximal volume of the erectile tissue the pressure within the corpora cavernosa rises to 80-90% of systolic blood pressure. As the pressure rises, emissary veins are compressed and venous outflow decreases. After reaching systolic blood pressure a decrease in arterial inflow and venous outflow occurs.
4) Rigidity phase - contraction of bulbocavernosus and ischiocavernosus raises the pressure in the cavernous body by up to several hundred mmHg. There is no blood flow in the erectile tissue.

24
Q

What are the neural pathways controlling erection?

A

Both infraspinal (reflex) and supraspinal (cortical) inputs control penile erection. Erection is largely parasympathetic (i.e. point)

Reflex erection is triggered by tactile genital stimulation. Afferent signals pass via the pudendal nerve to integrating centres in the sacral spinal cord (S2-S4). This sends efferent signals along parasympathetic fibres via the inferior hypogastric plexus. Activation of parasympathetic fibres releases nitric oxide through a cGMP mechanism causing arterial dilatation in the penis so that the sinusoids of the corpora cavernosa and corpus spongiosum become engorged with blood. This reflex is largely independent of cortical inputs. Psychogenic erection involves psychic (i.e. visual) stimuli that activate descending inputs onto the inferior hypogastric plexus.

25
Q

What neural pathways mediate ejaculation?

A

Emission of the glandular secretions occurs in a definite sequence. During erection, secretions from the bulbourethral gland are discharged to lubricate the urethra. Prostate secretions are followed by testicular secretions containg sperm, and subsequently the seminal vesicles which contribute the alkaline component of the ejaculate.

Ejaculation is triggered by stimulation of tactile receptors in the glans penis causing impulses to pass along afferent nerves to sympathetic centres in the lumbar spinal cord (T12 - L2). These initiate impulses that return along sympathetic fibres. Sympathetic activity leads to contraction of the smooth muscle of the epididymis, vas deferens and secretory glands propelling spermatozoa and glandular secretions into the urethra. Contraction of the bulbospongiosus and ischiocavernosus muscles due to reflex activity in somatic motor nerves leads to pulsatile emission of seinal fluid from the urthra.

26
Q

At what stage of development does the male reproductive system form?

A

Reproductive system of both sexes is indifferent until week 7. Primordial germ cells which are located at the base of the allantois migrate to the gonadal ridge. Differentiation occurs from week 7 onwards.

27
Q

What causes development of the male gonads?

A

In the genetic male (XY) the presence of the testis determining gene - called SRY - located on the Y chromosome causes differentiation of the gonads into testes, resulting in the incorporation of the primordial germ cells and supporting cells to form seminiferous cords. At this stage, the fetus has primordial genital ducts for both the male (Wolffian ducts) and female (Mullerian ducts). Testosterone secreted by the developing foetus causes development of the Wolffian ducts which go on to form internal genitalia (epididymis, vas deferens, seminal vesicles and prostate). Mullerian inhibiting hormone (also produced by the testes) causes regression of the Mullerian ducts.