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Human reproduction and fertility > Reproductive systems and gametogenesis > Flashcards

Reproductive systems and gametogenesis Flashcards

1
Q

Hypothalamic-pituitary-gonadal axis

A

Part of the endocrine system
Endocrine glands secrete hormones into bloodstream which travel + act on target organs

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2
Q

Axis

A

Multiple endocrine glands working together as a system to regulate development, reproduction + ageing

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3
Q

Hypothalamus

A

Component of the forebrain that regulates many core body functions

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4
Q

What functions does the hypothalamus regulate?

A

Metabolism
growth
reproduction
stress

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5
Q

What peptide hormone does the hypothalamus release?

A

Gonadotrophin releasing hormone
GnRH

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6
Q

What cells make up the anterior pituitary?

A

thyrotropes
somatotropes
gonadotrophs
corticotropes
lactotropes

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7
Q

Thyrotropes

A

TSH

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8
Q

Somatotropes

A

Growth hormones

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9
Q

Gonadotrophs

A

FSH
LH

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10
Q

Corticotropes

A

ACTH

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11
Q

Lactotropes

A

Prolactin

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12
Q

Gonadotrophin releasing hormone

A

stimulates gonadotroph proliferation and hormone production
sets up signalling cascades that cumulate in expression of FSH/LH

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13
Q

What stimulates gonadotrophin release?

A

Increased calcium

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14
Q

What happens when FSH/LH stimulate the ovaries/testes?

A

produce steroid hormones
oestrogens and androgens

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15
Q

What are the three main types of sex steroid?

A

progestagens
androgens
oestrogens

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16
Q

What precursor are all sex steroids derived from?

A

cholesterol

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17
Q

What is the action of sex steroids dictated by?

A

tissue-specific receptors

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18
Q

What are the sex steroids essential for?

A

reproduction
gametogenesis
maintenance of secondary sex characteristics

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19
Q

Inhibin and activin

A

bind to specific receptors on gonadotrophs
exert opposing actions on FSH expression
inhibin modulates activin activity

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20
Q

What family are inhibin and activin part of?

A

TGF-beta

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21
Q

Consequences of gonadal atrophy

A

destruction of GnRH neurons
generation of genetically null GnRH mice
immunisation against GnRH peptide

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22
Q

How is GnRH released?

A

pulsatile manner
pulses begin at puberty
controlled by pulse generator in hypothalamus

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23
Q

How can alterations in the output of LH/FSH be achieved?

A

increasing/decreasing amplitude or frequency of GnRH pulses
modulating response of gonadotrophs to pulses

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24
Q

Kisspeptin

A

positive regulation og GnRH secretion
master player of control of reproduction
encoded by kiSS1

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25
Q

What does kisspeptin do?

A

binds to GPR54 receptor found in all GnRH neurons
potent GnRH stimulator
receptor found in many tissues

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26
Q

kiSS-1+ neurons

A

direct targets of steroid hormones
binding results in negative feedback of kisspeptin and therefore GnRH

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27
Q

RFamide-related peptide (RFRP-3)

A

negative regulator of GnRH secretion
mammalian orthologue of gonadotrophin inhibitory hormone

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28
Q

What does RFRP-3 act on?

A

gonadotrophs, kiss1 neurons and GnRH neurons in the hypothalamus
receptotrs also in gonads

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29
Q

What does RFRP-3 do?

A

results in reduced GnRH output
suppresses the signalling cascade within gonadotrophs that express LH/FSH

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30
Q

Control of puberty onset

A

kisspeptin-GnRH axis becomes fully activated- pulse generator mechanism allows pulsatile release
metabolic gating

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31
Q

What role does leptin have in puberty onset?

A

necessary for puberty to proceed but isn’t sole requirement
acts on GnRH neurons indirectly

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32
Q

Spermatogenesis

A

the production of spermatozoa from spermatogonial stem cells

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33
Q

Testes

A

houses seminiferous tubules, the site of spermatogenesis
temperature important

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34
Q

Epididymis

A

sperm storage and maturation

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35
Q

Vas deferens

A

transport of sperm from epididymis to urethra during ejaculation

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36
Q

Seminal vesicle

A

produces a mucus secretion which aids the mobility of sperm

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37
Q

Prostate gland

A

produces an alkaline secretion that neutralises the acidity of any urine in the urethra and aids the mobility of sperm

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38
Q

Urethra

A

tube that carries urine and sperm out of the body

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39
Q

What are the two functions of the testes?

A

produce androgens and other hormones for sexual differentiation
produce spermatozoa for sexual reproduction

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40
Q

Structure of seminiferous tubules

A

coiled tubules lined with seminiferous epithelium
site of spermatogenesis + location of sertoli cells

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41
Q

What does the stroma of testes consist of?

A

blood vessels, lymph and leydig cells

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42
Q

Leydig cells

A

in stroma
synthesize and secrete steroid homrones

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43
Q

Primordial germ cells

A

gamete precursors
identifiable at 3 weeks gestation

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44
Q

What is the fate of PGCs as gestation goes on?

A

expands by mitosis and migrates to the genital ridge primordium
a second set of cells migrates in germinal epithelium which will become sertoli/granulosa cells

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45
Q

Spermatogenesis overview

A

begins at puberty, produces 100 million a day
involves mitosis and meiosis

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46
Q

What is the final differentiation step of spermatogenesis called?

A

spermiogenesis

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47
Q

What does spermatogenesis produce?

A

4 mature spermatozoa
identical in size but not genetically

48
Q

Spermatogonial stem cells

A

adult stem cells
self-regenerating pool undergoing rounds of mitosis
groups of morphologically distinct cells emerge- A and B

49
Q

Type A spermatogonia

A

produce a clone of 16 cells which enter further rounds of mitosis with some differentiation in between

50
Q

Type B spermatogonia

A

go on to become primary spermatocytes

51
Q

Spermiation

A

fully differentiated sperm released into the lumen

52
Q

Acrosome cap

A

important for fertilisation
formed by golgi apparatus

53
Q

Tail

A

required for motility
formed by one of centrioles elongating

54
Q

Mid-piece

A

contains the mitochondria

55
Q

Central axoneme

A

made up of bundles of fibres

56
Q

What changes take place during spermiogenesis?

A

nucleus changes to fit into sperm head
cytoplasm and organelles removed by sertoli cells via phagocytosis
golgi apparatus → acrosome cap
centriole elongation → tail

57
Q

Effects of spermatogenesis on transcription

A

X and Y chromosome transcription stops before meiotic divisions
autosomal transcriptional activity ceases during spermiogenesis

58
Q

Chromatin remodelling in spermatogenesis

A

histones replaced by protamines
tightly compressed compressed chromatin with no gene expression

59
Q

Blood-testis barrier

A

barrier to macromolecules formed by sertoli cells tight junctions
separates testes into basal and adluminal compartments

60
Q

When do spermatogonia become spermatocytes?

A

once they enter meiosis and move away from the basement membrane
cross into adluminal compartment where they receive all nutrients from sertoli cells

61
Q

Adluminal compartment

A

immune-privileged site
protects haploid cells from potential immune rejection

62
Q

Duration of spermatogenic cycle

A

every section of seminiferous tubule produces sperm every 16 days

63
Q

Spatial and temporal organisation of spermatogenesis

A

set lag time between development of clones
different sections of tubule- different stages
gap junctions between sertoli cells provide communication

64
Q

Passage through epididymis

A

takes 5-11 days
sperm acquire potential to swim + fertilise oocyte (dependent on androgens)

65
Q

Where are mature sperm stored?

A

in the tail end of the epididymis ready for ejaculation via the vas deferens

66
Q

Activin A in spermatogenesis

A

positive feedback on pituitary FSH production
autocrine effects on sertoli cells
paracrine effects on spermatogenic clls

67
Q

Inhibin B in spermatogenesis

A

stimulatory effect on leydig cells
negative feedback on FSH production
acts as activin antagonist
indicative of sperm count

68
Q

Prolactin in spermatogenesis

A

enhances LH stimulation of leydig cells

69
Q

Oestrogen in spermatogenesis

A

required for fluid absoprtion in testes

70
Q

Oxytocin

A

stimulates seminiferous tubule motility

71
Q

What are steroids converted to in the testes?

A

more potent dihydrotestosterone
or oestrone + oestradiol 17B

72
Q

What do the hormones produced from steroid conversion do in sperm?

A

act to stimulate sertoli cells
also secretes into the blood or tubular fluid

73
Q

What is testosterone essential for in sertoli cells?

A

maintenance of blood-testes barrier
sertoli-spermatid adhesion
spermatid elongation
spermiation
production of testicular fluid

74
Q

What does testosterone do in the tubule lumen?

A

binds to androgen binding proteins secreted by sertoli cells
complex travels to + stimulates ducts of testes

75
Q

Testosterone in leydig cells

A

acts autocrinologically in a negative feedback loop

76
Q

During spermatogenesis which cell type are the first to become haploid?

A

primary spermatocytes

77
Q

What are the key hormones acting in the male reproductive system?

A

testosterone + oestogen
activin A and inhibin B
FSH and LH
GnRH
prolactin
oxytocin

78
Q

Oogenesis

A

production of oocytes from primordial germ cells

79
Q

Uterus

A

supports pregnancy

79
Q
A
80
Q

Ovaries

A

produce oocytes and secrete hormones

81
Q

Ovarian stroma

A

connective tissue, smooth muscle, stromal cells and developing follicles

82
Q

Uterine tube

A

connects ovaries and uterus
important for transport of oocyte/embryo

83
Q

Two main reproductive functions of the female genital tract

A

gamete production and transportation
site of implantation and support of foetal development

84
Q

How does the episodic nature of the menstrual cycle facilitate its functions?

A

first oestrogenic half- matuer oocyte produced + ready for fertilisation
second progestagenic half- uterus made ready to allow implantation + support pregnanct

85
Q

How does adult ovarian function differ from testicular function?

A

far fewer oocytes produced
ovulation occurs episodically ratehr than continuously
ovulation stops at menopause- sperm production declines but continues

86
Q

What are the timings of oogenesis in general?

A

mitotic divisions all occur during foetal development
girls born with primary oocytes arrested at prophase I
resumption of meiosis + oocyte development occurs after puberty

87
Q

Products of meiosis II in oocytes

A

asymmetric
produce one mature oocyte and two polar bodies that contain chromosomes but little cytoplasmic material

88
Q

Stages of follicle development

A

primordial follicle → preantral follicle → antral follicle → preovulatory follicle

89
Q

What is the follicle?

A

provides appropriate supportive environment for a developing oocyte
female version of seminiferous tubules supporting sperm development

90
Q

Primordial → preantral follicle
mRNA + rRNA

A

large amounts produced to build organelles and generate protein stores

91
Q

Primordial → preantral follicle
granulosa cells

A

proliferate to form thick layer around oocyte
contact between granulosa cells and oocyte maintained through cytoplasmic processes

91
Q

Primordial → preantral follicle
glycoproteins

A

secreted by oocytes
condense to form the zona pellucida

92
Q

Primordial → preantral follicle
ovarian stromal cells

A

condense to form the thecal layer
seperated from granulosa layer by membrane propria

93
Q

Antral follicle development

A

thecal layer expands and further develops to form two layers: theca interna and externa
granulosa cells secrete flluid
increasing follicle size due to antrum
oocyte continues to synthesise RNA + make proteins

94
Q

Cumulus oophorus

A

granulosa layer that surrounds the oocyte
suspended in follicular fluid by a thin stalk that connects to mural granulosa cells

95
Q

Communication between granulosa cells and oocyte

A

connected via cytoplasmic processes
gap junctions between adjacent granulosa cells at oocyte surface
extensive network allows transfer of amino acids + nucleotides to oocyte
resembles sertoli cell-spermatogenic complex

96
Q

How is very early primordial follicle development stimulated?

A

locally via growth factors and cytokines
few follicles recommence growth every day

97
Q

Regulation of follicle development

A

dependent on pituitary after early stage
FSH- preantral
LH- antral

98
Q

LH and FSH in follicle development

A

only cells in theca interna bind LH
only granulosa cells bind FSH
stimulate follicles to grow + eggs to mature

99
Q

What is the effect of LH stimulation on thecal cells?

A

production of androgens androstenedione + testosterone

100
Q

What is the effect of FSH stimulation on granulosa cells?

A

conversion of androgens from thecal cells to oestrogens
oestradiol 17B + oestrone

101
Q

What is the effect of granulosa cells expressing LH receptors later in the menstrual cycle?

A

LH stimulation resulting in synthesis of progesterone

102
Q

How is the oestrogen surge created?

A

increase in androgens cause granulosa cells to proliferate and increase oestrogen production
oestrogens themselves also promote granulosa proliferation

103
Q

What is the purpose of an oestrogen surge?

A

exerts positive feedback
stimulates LH surge

104
Q

Ovulation

A

characterised by LH surge which coincides with expression of LH receptors on granulosa cells

105
Q

Effects of LH surge

A

entry into preovulatory phase of growth
nuclear membrane breaks down + meiosis resumes up to metaphase II
cytoplasmic maturation occurs
follicle ruptures + oocyte carried out in follicular fluid

106
Q

Luteal phase

A

granulosa cells switch from oestrogen to progesterone production under LH stimulation
positive feedback loop- exponential increase in progesterone

107
Q

What is the effect of the progesterone increase in the luteal phase?

A

depresses growth of less mature follicles
promotes transition to progestagenic phase of ovarian cycle

108
Q

What is the corpus luteum?

A

the empty follicle after collapsing and becoming highly vascularised post-ovulation
secretes inhibin and oxytocin to maintain it + luteolysis
undergoes luteolysis

109
Q

What do granulosa cells become and do in the corpus luteum?

A

large lutein cells
synthesize progestagens

110
Q

What do thecal cells become and do in the corpus luteum?

A

small lutein cells
produce progesterone + androgens

111
Q

How does oestradiol act in different ways during the menstrual cycle?

A

low concs- negatively regulates LH expression
high concs- positively regulates LH expression

112
Q

Main effects of progesterone

A

enhances negative feedback of oestradiol + blocks its positive feedback
acts on both hypothalamus + pituitary

113
Q

How is FSH secretion from the pituitary regulated?

A

increase in progesterone results in fall in FSH
activin positively regulates
inhibin B selectively negatively regulates + antagonise activin

Human reproduction and fertility (5 decks)

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