Lecture 15 - Male Reproduction Flashcards

1
Q

What commonalities are found between sexes?

  1. formation of gametes via gametogenesis
    - how many chromosomes are in gametes and what cells do they come from (how many chromosomes are in those cells)?
    - what is the process of forming gametes vs forming normal somatic cells (how many times is DNA replicated and how many cellular divisions are there?)
A

Gametes with 23 chromosomes are produced from gonad cells with 46 chromosomes.

Gametogenesis involves Meiosis
* DNA replicated once
* Cells undergo division twice
* haploid for humans
* 4 daughter cells (2:2)

In contrast: Mitosis = normal somatic cell division
* DNA replicated once
* Cells undergo division once
* diploid for humans
* 2 identical daughter cells

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2
Q

What commonalities are found between sexes?

  1. Hypothalamic/pituitary control of reproduction
  • what is the pathway of the production of reproductive hormones in both females and males
A
  • controlled by the hypothalamic/pituitary pathway
  • stimulus: internal and environmental stimuli
  • hypothalamus: produces GnRH, gonadotropin releasing hormone
  • anterior pituitary: produces wither LH, luteinizing hormone, or FSH, follicle-stimulating hormone
  • then these hormones go to different pathways for males and females to produce gametes (add?)
  • note: there are negative (and sometimes positive) feedback loops that control these pathways
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3
Q

how does the anterior pituitary control which hormone, LH or FSH, it will produce?

A
  • depends on pulses of the GnRH secreted neuron which synthesizes and secretes FSH and LH
  • remember, since the hormone is secreted from the hypothalamus, this region has modified neurons that secrete the neuroendocrine hormones thus have neurological characteristics
  • the size and frequency of GnRH pulses, as well as the feedback from eventual androgens and estrogens control which hormone is produced
  • low freq. of GnRH = FSH release
  • high freq. of GnRH = LH release
  • the pulse frequency / amplitude changes during different stages in life and thus produces different hormones during these diff stages
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4
Q

what is the primary organ in XY males produces the gametes?

what is special about males in terms of producing semen

what is the pathway from development of sperm to ejection

A
  • the testes produce the male gametes, sperm
  • in males only, the production of semen is a collective task shared by both the reproductive and urinary systems
  • it develops in the testes (reproductive) and travels through the vas deferens duct (2), seminal vesicle (2), prostate gland (1), bulbourethral gland (2), to then travel in the penis in the urethra (1- urinary) to then be ejected into the external environment
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5
Q

how is sperm produced:

  • what organ produces sperm
  • where in that organ is it produced and where does it go to mature
  • what is the optimal temperature for production and how is it maintained?
  • how long does it take to mature, and how many are made a day
A
  • the testes produce sperm
  • made in the seminiferous tubules and then travel to the epididymis to mature
  • optimal temp is 2-3ºC below body temp (around 35ºC instead of 37ºC)
  • this is achieved by the scrotum which is the layer of skin around the testes and is exposed to the external environment. there is also a capillary network that helps with this temp regulation
  • it takes around 64 days to be mature, around 200 million/day
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6
Q

how is sperm produced:

  • what are the main elements in a zoomed in image of a seminiferous tubule in the testes that produce sperm (4)
A
  • spermatogonium: starting point germ cell. precursor of sperm cell production. present on the border of the seminiferous tubule, and then mature inwards via mitosis/meiosis to produce sperm cells.
  • sertoli/ sustentacular cells: support sperm development. adjacent to strips of spermatogonial cells.
  • leydig/interstitial cells: secrete testosterone. present right outside of the seminiferous tubule
  • capillaries: also present right outside the seminiferous tubule
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7
Q

why aren’t there capillaries inside the seminiferous tubule

A
  • sperm are haploid and have novel/unique proteins on its outside coat
  • these characteristics make sperm look foreign to our immune cells
  • if the capillaries were inside and with the sperm, there could be an autoimmune reaction where our own immune system eliminates sperm we produce
  • thus to avoid this, sertoli cells create tight junctions. These tight junctions seperate the cell into two halves: 1 half = contains spermatogonia (early-stage germ cells), allowing these cells to access nutrients and other factors directly from the bloodstream. other half = contains developing germ cells (e.g., spermatocytes, spermatids, and spermatozoa), which are isolated from the bloodstream.
  • as such there is a blood testis barrier between the developing sperm cells (germ cells) from the bloodstream.
  • this barrier ensures that no immune cells within the bloodstream ever reach in contact with the sperm cells
  • these sertoli cells then absorb any nutrients in the bloodstream that the developing sperm needs and filters it before sending it to the cell.
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8
Q

how does sperm develop via spermatogenesis (4 steps)

A
  • spermatogonia, germ cells that are developed in the male womb (fetal), are formed and surround the border of the seminiferous tubule
  • these cells keep dividing throughout life via mitosis (diff than females)
  • mitosis makes two identical daughter cells. one of these cells continues with meiosis to produce sperm (this cell is known as the primary spermatocyte) and the other is going to stick around and keep dividing, so there is always a pool of sex cells in males
  • the primary spermatocyte (2n) goes through meiosis 1 (n x 2 – secondary spermatocytes) and then meiosis 2 (n – spermatids), thus creating 4 spermatids produced from one starting/primary spermatocyte
  • spermatids undergo spermatogenesis to form spermatozoa/sperm (n) = this is when the spermatids loose a cytoplasm and gain a tail to essentially look like sperm. the sperm gets pinched into the lumen of the seminiferous tubule
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9
Q

what does the anatomy of a spermatozoa/sperm look like (3 sections, 4 key structures)

A
  • the nucleus forms most of the head of the sperm
  • there is the acrosome which is at the tip of the head. contains enzymes that is important for fertilization (contains hyaluronidase
    and acrosin which
    breakdown the the zona
    pellucida, a glycoprotein
    coat that covers the
    oocyte). is derived from the golgi apparatus.
  • we have a mitochondrial spiral that is on the midpiece between the head and the tail – this is important for providing the sperm with energy to swim
  • then there is the tail aka the flagellum
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10
Q

what is in semen?

what are the three glands (what type of gland are they: exocrine or endocrine) and what substances do they release in the semen and why?

A
  • semen serves to transport, nourish, and protect sperm on their journey through the female reproductive tract to fertilize an egg.
  • there is about 1% spermatozoa/sperm and the rest is secretions from accessory glands
  • the other 99% is water, lubricant such as mucous, buffers to neutralize acid, nutrients (fructose, citric acid, vit C, carnitine), enzymes, zinc etc.
  • the seminal vesicles, prostate gland, bulbourethral gland are exocrine glands – they do not produce hormones, but produce secretions through ducts into lumen
  • the seminal vesicle produces fructose and other nutrients in the semen for energy for the sperm to swim.
  • the prostaglandins/prostate glands help push the semen from the male tract to the female tract. this structure has smooth muscle around it which helps contract the muscle and propel the semen along.
  • the bulbourethral gland helps produce buffers, alkaline secretions, to help neutralize acid. the urine is sometimes acidic, and since the semen goes through the urethra, it needs to neutralize this to keep the ph of the sperm at a healthy environment. it also helps neutralize the acidic environment of the vagina.
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11
Q

what are the negative feedback loops in the hypothalamus pituitary axis?

A
  • when testosterone is produced, it inhibits production of LH, FSH, (in anterior pituitary) and GnRH (in hypothalamus)
  • when inhibin is produced, it inhibits FSH only.
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12
Q

what are the roles of FSH and LH

A

FSH:
- binds to the membrane receptors on testes and stimulates sertoli cells which then support sperm development, secrete inhibin (this hormone inhibits FSH release through neg feedback), secretes androgen-binding protein (helps to concentrate androgens in testis)

LH:
- binds to leydig cells on the outside of the testes to produce testosterone
- neg feedback to further LH, FSH, and GnRH production

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13
Q

what is the testosterone secretion throughout life like in males?

testosterone / INSL3 (insulin like factor 3)

A

fetal = peak –> differentiation
neonatal (right after birth) = peak –> we don’t know why
pre-puberty = dip
puberty to late adulthood = big peak –> for reproduction
post adulthood/senescence/seniors = dip

  • testosterone is always secreted at some level in males at all times
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14
Q

what is the secretion of other hormones like in males throughout life
- FSH
- LH
- Inhibin
- anti mullerian hormone, AMH

A
  • LH and FSH follows the secretion patterns of testosterone as these hormones are upstream of testosterone
  • inhibin is used to inhibit FSH. Thus it is used as negative regulation in puberty and peaks then along FSH. we don’t know the pattern of inhibin secretion before puberty that well.
  • AMH is high all throughout XY life, but decreases after puberty. we will discuss this further in future lectures
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15
Q

how does testicular volume and content in the testes (interstitial tissue, germ cells, sertoli cells) vary between males at birth, pre-puberty, and during puberty?

A

testicular volume:
- birth: 0.3-0.7 ml
- pre-puberty: 0.5-1.5 ml
- puberty: 10-20 ml

content in testes:
- birth & pre-puberty = similar contents, mainly sertoli cells
- puberty = mainly germ cells

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16
Q

what is hypogonadism

A
  • condition which results in the decrease functional activity of the testes in males
  • correlates with decrease production of androgens, inhibin B, AMH, and/or impaired sperm production
17
Q

what is primary vs secondary hypogonadism? what are the therapies for each?

A

primary:
- damage is done to the testis
- thus dec. testosterone
- this causes inc. LH & FSH & GnRH since there is no negative feedback
- therapy: give exogenous testosterone to individual

secondary:
- damage is done to either the hypothalamic neurons in the brain’s hypothalamus and the anterior pituitary –> genetic defects, cancers, etc.
- dec. GnRH = dec LH & FSH = dec testosterone
- therapy: give exogenous testosterone to individual, or use another method to control GnRH and LH and FSH

18
Q

recall previous unit: testosterone is a steroid hormone
what is the pathway?

A
  • cholesterol –> 4 units –> testosterone –> with alpha-reductase enzyme produces dihydrotestosterone (DHT)
  • cholesterol –> 1 unit –> progesterone –> 2 units –> testosterone –> with aromatase enzyme produces estradiol
19
Q

what does testosterone and other related steroids do (like DHT)?

  • sex specific tissues (3)
  • other reproductive effects (2)
  • secondary sex characteristics (3)
  • non-reproductive effects (3)
A

Sex-specific tissues:
❑Promotes spermatogenesis
❑Maintains and stimulates secretion from prostate and seminal vesicles
❑Maintains reproductive tract

Other reproductive effects:
❑Increases sex drive
❑Negative feedback effects on GnRH, LH (and FSH) secretion

Secondary sex characteristics:
❑Male pattern of hair growth (including baldness)
❑Promotes muscle growth
❑Increases sebaceous gland secretion

Non-reproductive effects:
❑Promotes protein synthesis
❑Increases aggression
❑Stimulates erythropoiesis

  • DHT, the related testosterone, is important for the function of the prostate gland and also for maintaining the external male genitalia
  • also has some implications in baldness
20
Q

what are inhibitors of 5alpha-reductase used to treat (2)

A
  • 5alpha-reductase is an enzyme required to convert testosterone to DHT
  • if we block this production w/ 5 alpha-reductase inhibitors we can inhibit some of the main functions of DHT: aka enlargement of prostate and baldness.
  • ex. Finasteride drug was used to treat prostate enlargement and also cure baldness by increasing hair growth
  • common name for Finasteride for hair growth purposes is known as Propecia
  • note: the blocking of DHT can help these two problems but can also be a problem to other DHT controlling pathways. ie. it can cause depression, loss of libido, and fatigue –> side effects