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RED > Week 2 > Flashcards

Week 2 Flashcards

1
Q

Formation of the female reproductive system

A

Development is indifferent until week 7
Primordial germ cells (PGCs) give rise to the gametes
PGCs appear around week 3 in epithelium of yolk sac
Weeks 3-7:
-proliferate by mitosis
-migrate by amoeboid movement to region of dorsal wall that will form the gonads (gonadal/genital ridges)
-migration is guided by chemotaxis

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2
Q

Female development = default pathway

A

Week 7 onwards:
-in males SRY is expressed from week 7
-in the absence of Y chromosome, female gonad develops

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3
Q

Formation of the ovary

A

Same influxes of cells as seen in male
Sex cord cells do not penetrate deeply- cluster around PGC (oogonia)- primordial follicles- granulosa
Mesonephric duct- vasculature and theca cells
There is no endocrine activity during ovarian development in the female foetus
Further development is dependent on the presence of normal germ cells

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4
Q

Turner’s syndrome

A

XO
Normal oocyte development requires both X chromosomes, oocyte death
Normal ovary development requires normal germ cells ovarian dysgenesis

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5
Q

Adult (post-pubertal) ovary

A

Produce oocytes
Produce hormones

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6
Q

Female germ cells

A

Primordial germ cell
Oogonium
Primary oocyte
Secondary oocyte
Mature (tertiary oocyte)

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7
Q

Oogenesis

A

Primordial germ cell- mitosis
Oogonia- mitosis
Primary oocytes- 1st Meiotic division
Secondary oocytes- 2nd Meiotic division

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8
Q

Timing of entry into meiosis

A

Males: meiosis is initiated post-puberty
Females: oogonia enter meiosis during fetal period
Controlled by stimulated by retinoic acid 8 gene (Stra8)- retinoic acid
Cytochrome P450 mediated metabolism of RA in males until puberty (Stra8 not activated until puberty in males)

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9
Q

Oogenesis is not continuous

A

Two Meiotic blocks
Primordial germ cell—migration to genital ridge during early development—> oogonium— in utero—> primary oocyte arrested at prophase I—ovulation —> secondary oocyte arrested at metaphase II—fertilisation—> female pronucleus and male pronucleus — pronuclear fusion—> zygote
After 1st Meiotic block primary oocytes enter a prolonged resting phase up to 50 years
Arrested long time can be damaged, Meiotic spindle can be damaged, complications in pregnancy with older mothers

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10
Q

Females are born with finite number of oocytes

A

Males: spermatogonial stem cells (as spermatogonia)
Females: all oogonia enter meiosis before birth- no ovarian stem cells- menopause
But at mid point of gestation a female feotus has 7 million oocytes in her ovaries

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11
Q

Female germ cells undergo clonal expansion then reduction (atresia)

A

PGC migration -170
8/40- 600 000
20/40- 7000000
Birth 2000000
Puberty 400000
Only 400 to 500 will be ovulated

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12
Q

Menopause

A

Peri-menopause/climacteric- period of reproductive change that precedes menopause- up 10 years
Falling oestrogen- rising FSH/LH
Common symptoms of menopause and perimenopause include:
-oligomenorrhea, mood changes- depression, anxiety, low self esteem, problems with memory or concentration (brain fog), loss of libido, vaginal dryness and pain, recurrent urinary tract infections, hot flushes and night sweats, difficulty sleeping, palpitations, headaches and migraines, muscle aches and joint pains, weight pain
Menopause- 51 years in UK- 12 months amenorrhea (Over 50), 24 months amenorrhea (under 50)
Oestrone predominates- adrenals, adipose- least potent

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13
Q

Consequences of oestrogen withdrawal

A

Loss of anti-PTH activity- bone catabolism- oesteoporosis
Change in blood lipid ratios- coronary thrombosis
Reduction in vaginal lubrication- dyspareunia
Behavioural/mood changes- endocrine, psychological

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14
Q

Hormone replacement therapy HRT

A

Usually combination of synthetic progesterone and oestrogen
Unopposed oestrogen- endometrial hyperplasia- endometrial cancer
Oestrogen only HRT is only suitable for women who have has a hysterectomy
Increased risk of breast/ovarian cancer and CV side effects

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15
Q

Meiotic divisions are asymmetrical

A

Division is asymmetric and leads to the production of polar bodies

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16
Q

Polar bodies

A

Both are relatively small and contain little cytoplasm
Excess genetic material
1st polar body is released just before ovulation
Presence of 2nd polar body released after fertilisation and the completion of 2nd Meiotic division

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17
Q

Oocytes develop within follicles

A

Two types of follicular somatic cells:
-granulosa (F) - sertoli (M)
-theca (F)- leydig (M)
Primordial follicle, primary follicle (pre-antral), secondary follicle (pre-antral), tertiary follicle (graafian/antral)

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18
Q

Folliculogenesis

A

Primordial follicle: primary oocyte surrounded by single layer of flattened granulosa (fetus)
From puberty a few primordial follicles begin to grow each day
375 days to ovulation
Oocyte begins to grow and synthesises proteins needed for oocyte maturation and first few days of development post fertilisation
Independent of menstrual cycle

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19
Q

Primary follicle

A

Granulosa cells become cuboidal; theca and zona pellucida become visible
Independent of menstrual cycle

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20
Q

Formation of the zona pellucida ZP

A

Glycoprotein layer- present around all mammalian eggs
Granulosa cell processes traverse through to the oocyte
ZP is important for sperm binding, induction of acrosome reaction and protection of the early embryo

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21
Q

Folliculogenesis 2

A

Secondary follicle: granulosa proliferate; theca forms two distinct layers- interna and externa; 5-15 follicles/cycle (dependent on menstrual cycle)
Tertiary follicle: granulosa secrete follicular fluid; oocyte surrounded by layer of corona radiata and on stalk of cumulus cells; only 1 dominant follicle/cycle. Dependent on menstrual cycle and hormones being produced

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22
Q

Extraovarian hormonal action HPG axis

A

From puberty:
Hypothalamus: secretes GnRH which acts on the
Anterior pituitary: secretes FSH, acts on ovary FSHR, stimulates development of follicles
LH acts on ovary LHCGR, stimulates follicle maturation, ovulation and development of the corpus luteum

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23
Q

Ovarian hormones

A

Oestrogens:
-growth of body and sex organs at puberty; development of secondary sexual characteristics
Reproduction: follicle maturation, preparation of the endometrium for pregnancy proliferation, thinning of cervical mucus
Progesterone: produced by corpus luteum (post ovulation), acts on uterus- completes the preparation of and maintain endometrium for pregnancy secretory
Numerous cytokines- inhibin A/B, activin, GDF9

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24
Q

Oestrogen production

A

Two cell hypothesis
Testosterone is produced by theca cells and diffuses to granulosa where it is converted to oestrogen by aromatase
LH increases cholesterol uptake by theca
FSH increases aromatase expression

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25
Q

Follicular/proliferative phase

A

Hypothalamus secretes GnRH
In response ant. Pituitary secretes FSH
Up to 15 follicles are rescued
Granulosa and theca cells develop in growing follicles
Produce oestrogen (thickens endometrium/ thins cervical mucus)
Oestrogen suppresses FSH production by the ant.pituitary (dominant follicle)
Granulosa in the dominant follicle express LHCG receptor
High levels of oestrogen at mid cycle causes LH surge from ant.pituitary

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26
Q

Ovulation

A

Resumption and completion of meiosis I
Secondary oocyte enter meiosis II arresting at metaphase
Increase in follicular fluid and number of granulosa
Cumulus oophorus loosens
Follicle wall weakens (stigma)- MMPs, plasminogen, collagenase, gelatinase
Ovulation- oocyte, ZP, cumulus
Cumulus- oocyte- complex picked up by fimbrae of uterine tube
30-36 hours

27
Q

Luteal (secretory) phase

A

Corpus luteum
Granulosa - large lutein cells- progesterone and oestrogen
Theca- many disperse to stromal tissue- small lutein cells- progesterone and androgens (aromatised) LHCG receptor
Endometrium becomes secretory
Negative feedback- progesterone, oestrogen LH/FSH levels low

28
Q

Pregnancy

A

Syncytiotrophoblast of embryo produces hCG- binds LHCGR on lutein cells maintains the corpus luteum
Produces progesterone (and oestrogen) to support pregnancy
Oestrogen/progesterone suppress ovulation
6/40 weeks- placenta takes over and the corpus luteum degenerates- corpus albicans

29
Q

Luteolysis

A

~12 days if there is no hCG production from an embryo, the corpus luteum degenerates forming the corpus albicans
Progesterone and oestrogen levels fall removing negative feedback and the cycle recommences

30
Q

What is a gamete

A

Mature haploid reproductive cell
Spermatozoa (sperm)
Oocyte (egg)
Germ cells
Gametogenesis

31
Q

Formation of the male reproductive system

A

Indifferent until week 7
Primordial germ cells (PGCs)
Diploid germ cell precursors
Arise during gastrulation
Epiblast derived

32
Q

Week 7 onwards

A

Male or female development
XY or XX
Presence of Y chromosome determines whether male or female
Y small not a whole gene

33
Q

SRY

A

Sex determining region Y gene
Testis determining factor TDF
Discovery- conserved across mammals
XY ‘females’ and XX ‘males’ have SRY mutations/deletions/translocations
Homologous gene in animals- female mice with SRY transgene show male development
Architectural transcription factor- cascade of gene expression- to form testes

34
Q

Testis development

A

Form week 7
Columns of cells from coelomic epithelium- proliferate and penetrate deep into medullary mesenchyme- primitive sex cords- express SRY
PGCs
Sex cord cells surround PGCs- seminiferous tubules- Sertoli cells
Migratory cells from mesonephric primordia- vasculature, leydig, myoid cells
Within seminiferous tubules: Sertoli cells from sex cord cells, prospermatogonia from PGC, inhibition of meiosis
Between seminiferous tubules: vascularisation and clusters of leydig cells form
SRY no longer expressed
Testes produce hormones which direct further development of male reproductive system (androgens/anti-mullerian hormone AMH)

35
Q

Post-pubertal testis

A

Two products: spermatozoa and hormones
Two compartments:
-within seminiferous tubules- sperm develop, Sertoli cells
Between seminiferous tubules- leydig cells

36
Q

Blood testis barrier BTB

A

Between basal and adluminal compartments of seminiferous tubule
Adherens, gap and tight junctional complexes link each Sertoli cell to its neighbour to form BTB
Develops during puberty prior to onset of spermatogenesis
Two functions:
-separates sperm from immune system preventing immune response (anti sperm antibodies and autoimmune orchitis), selective transport of ions and small molecules (maintains controlled microenvironment for spermatogenesis to occur)

37
Q

Spermatogenesis

A

Sperm are highly specialised, complex cells produced in large numbers
In human males: 100 million per day
3 phase: proliferation, division and differentiation

38
Q

Proliferation phase

A

At puberty, prospermatogonia are reactivated and undergo mitosis in basal compartment of tubule
As spermatogonia (spermatogonial stem cells SSC)= reservoir of self renewing stem cells
Form a spermatogonia= start of spermatogenesis

39
Q

Mitotic proliferation

A

Each A spermatogonium undergoes mitosis to form type B spermatogonium which divide again to form primary spermatocytes
Number of mitotic divisions is species specific

40
Q

Division phase (meiosis)

A

Primary spermatocytes move into adluminal compartment passing through BTB
Undergo first Meiotic division 24 days
Form two secondary spermatocytes- 2nd Meiotic division to form haploid round spermatids

41
Q

Differentiation (spermiogenesis)

A

Round spermatids elongate to form elongated spermatids and finally mature spermatozoa
Formation of specialised sperm structures: acrosome, flagellum, centrioles, mitochondria, nucleus, cytoplasm

42
Q

Acrosome

A

Formed from Golgi apparatus
Contains hydrolytic enzymes- acrosome reaction
Receptor for fusion

43
Q

Flagellum

A

Sperm movement- female tract and penetration of the egg vestments
Centrioles migrate to opposite end of nucleus to acrosome
Distal centriole forms axoneme (central unit flagellum)
Proximal sperm centriole forms the spindle for the 1st mitotic division of the embryo

44
Q

Mitochondria

A

Energy for motility- helically arranged around first part of flagellum (midpiece)

45
Q

Nucleus

A

Sex determination (X or Y bearing)
Sperm DNA becomes highly condensed- histones replaced by protamines

46
Q

Cytoplasm

A

Superfluous cytoplasm forms residual body (cytoplasmic droplet) which is phagocytosed by Sertoli cells

47
Q

Consequences of sperm changes

A

Sperm transcriptionally and translationally inactive
Transcriptionally- DNA too condensed
Translationally- cant make proteins
Very dependent on environment

48
Q

Spermiation

A

Cells are released into lumen

49
Q

Kinetics of spermatogenesis

A

Human-whole process takes 64 days
Duration is species specific but constant
Controlled by germ cells
Spermatogenic wave

50
Q

Rat spermatogenesis in mouse testis

A

Injected rat SSC carrying reporter gene into immunodeficient sterile mice
Spermatogenesis occurred in all the mice
Rat sperm in mouse epididymis and with normal morphology
Kinetics 52 days in rat, 35 days in mouse
Still took 52 days in mouse so must be controlled by germ cells not environment
Xenografts?

51
Q

Products of the testis

A

Androgens- mainly testosterone
-embryonic development of reproductive system, reproductive function, sexual function
Oestrogens- small amount in human males
Cytokines- inhibin, AMH (anti muellarian hormone) /MIS

52
Q

Androgens (testosterone)

A

Steroid hormones, lipophilic
Produced by Leydig cells
Blood, lymph (accessory sex glands), seminiferous tubules
Converted to dihydrotestosterone in Sertoli cells (5a-reductase)
Some binds to androgen receptors in Sertoli cells drives spermatogenesis
Some binds to ABP (androgen binding protein)- high conc of testosterone and carrier of testosterone in testicular fluid
Regulation of HPG axis

53
Q

Inhibin

A

Produced by Sertoli cells
Represses FSH production by anterior pituitary gland

54
Q

AMH/MIS

A

Produced by Sertoli cells
Embryonic role in development of reproductive system

55
Q

Puberty- HPG axis

A

At puberty the hypothalamus begins to secrete gonadotrophin releasing hormone GnRH
GnRH induces the anterior pituitary to produce luteinising hormone LH and follicle stimulating hormone FSH
LH binds to LHCG receptors on leydig cells and induces them to produce testosterone which moves to the tubules and binds to the androgen receptor on Sertoli cells
FSH binds to the FSH receptor on Sertoli cells (>300 FSH responsive genes)
Induces expression of AR (androgen receptor)
Also stimulates production of ABP and inhibin

56
Q

Sperm maturation and transport

A

Spermatozoa leave the testis immotile and unable to recognise or bind an egg
Need to undergo maturation in the male tract and capacitation in the female tract

57
Q

Epididymis

A

Seminiferous tubules-> rete testis-> epididymis - single tube through which all sperm pass
Most of the fluid is reabsorbed (100X conc)- oestrogen
Sperm passage takes 10-14 days- sperm maturation
Epididymis plays active role- provides many molecules necessary for sperm to acquire fertilising ability and motility- androgen dependent
Segmented- caput (head), corpus (body), cauda- storage
Caput- motility, corpus- fertilising ability, cauda- storage
Humans have small cauda

58
Q

Vas deferens/ductus deferens

A

Densely packed with little fluid
Storage reservoir
Vasectomy

59
Q

Ejaculation

A

Sperm and seminal plasma= semen
Approx 3 ml in human containing ~100million sperm
Seminal plasma is secreted by the accessory sex glands
Transport, nutrition, buffering, antioxidants
Fractions- prostate, vas deferens, seminal vesicles
STIs

60
Q

Seminal vesicles

A

Sac-like glands
Empty upon ejaculation into ejaculatory duct
Provides majority of ejaculate volume (humans)
Fibrinogen like substrate- ejaculate clotting

61
Q

Prostate

A

Solid tissue mass- secretes during copulation
Alkaline secretions high in zinc- important for cell functions
Enzymes for ejaculate clotting (holds in place for fertilisation) and liquefaction (flows back out)

62
Q

Bulbourethral gland (Cowper’s gland)

A

Pre-ejaculate -alkaline neutralises acidic urethra urine is acidic
Lubrication
Neutralisation

63
Q

Capacitation

A

Pivotal experiments by Austin and Chang 1951
‘Sperm must undergo some form of physiological change or capacitation before it is capable of penetrating the egg’

Hyperactivtaion (tail)
Acrosome reaction (head)
Zone penetration
Sperm egg fusion

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