lecture 2: female tract and ovaries Flashcards

1
Q

What are the components of the female human reproductive tract?

A
  • ovary
  • fimbrium
  • fallopian tube (oviduct in other species)
  • uterus
  • cervix
  • vagina
  • vulva: clitoral hood, clitoris, urethral opening, labia minora, vaginal opening, labia majora, perineum, anus
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2
Q

What are differences between cow reproductive tract and human reproductive tract?

A
  • ovary - oviduct tightly bunches up like a ball of spaghetti that, dissected, is a very long tubule structure, ~25cm
  • long uterine horns with relatively small uterine body - bification
  • fornix - next to the cervix, blind end around that structure
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3
Q

What are features of the female rat reproductive tract?

A
  • very small ovary surrounded by a lot of fat
  • oviduct rolled in ball
  • extremely long uterine horns (short in human)
  • very little uterine body
  • allows for more foetuses
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4
Q

What is the reproductive tract of a female marsupial?

A
  • highly interesting
  • ovary at the top, oviduct not quite as clear
  • two uteri, independent
  • two independent cervix
  • number of vagina: anterior vagina, lateral vagina, median vagina
  • driven by the ureter: during development in the marsupial the ureter goes through the middle so the two Mullerian ducts which fuse in mammals to make the uterus, cannot fuse in marsupials
  • mutliple vaginae allow storage of sperm, mate with multiple males
  • very different to standard mammal
  • can also have a copulatory plug - same as in rats and mice ~24 hours
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5
Q

What is the anatomy of the female reproductive tract?

A

• ovaries (mono or polyovular)
→ humans generally have one egg, mono, poly would be e.g. rat and results in litters
• regionally specialised duct(s)
→ paired Mullerian ducts
→ fusion of ducts (varies with species)
→ amount of eggs released correlates to amount of fusion - polyovular species have less fusion allowing more foetuses to implant in the tract, while monoovular humans have lots of fusion
• variation in number of embryos
• good vascular supply to ovary and uterus (varies with reproductive status)
• same main hormones across species e.g.
→ oestrogens
→ progestagens
→ gonadotrophins
→ prostaglandins
• but timing and location of expression differs

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6
Q

What does the follicle make?

A

oestrogen

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7
Q

What does the Corpus luteum make?

A

progesterone

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8
Q

What is the Corpus albicans?

A

regressing CL

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9
Q

What is a feature of the myometrium?

A

muscular

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10
Q

What is a feature of the endometrium?

A

secretory

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11
Q

What is the cervix made of?

A

connective tissue

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12
Q

What is the role of cervical mucus?

A

regulates sperm passage in the external of cervix

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13
Q

What are the main features of the vaginal wall?

A

muscular tube with epithelial lining responsive to E2

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14
Q

Why is the fallopian tube or oviduct important?

A

Location of fertilisation

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15
Q

How big is an ovary?

A

5cm - bovine ovary
follicle dark spot, large
CL- ovulation point in the centre, protudes from the ovary, vascularised, very orange, taken over almost half the ovary
regressing CL

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16
Q

What is the basic structure of the ovary?

A

continuous process - at any time point always follicles at each stage
primordial follicle → primary follicle → secondary follicle → early tertiary follicle → atretic follicle → graatian follicle → ovulation → cumulus with egg → corpus luteum → corpus albicans

• ovoid shape 
• surface of coelomic epithelium over tunica albuginea 
• cortex
→ germ cells 
→ follicles
→ corpora lutea (CL)
→ corpora albicans 
→ interstitial glands 
→ stroma 
• medulla right in the centre of the ovary 
→ fibrous connective-tissue stroma 
→ blood vessels 
→ nerves
17
Q

What is folliculogenesis?

A

• in utero: primordial germ cells migrate to the ovary
• form structures called primordial follicles
• can be maintained in the ovaries for 40 or 50 years/until required
• if and when they get the signal to be triggered they will start going through process of folliculogenesis
• primary: gonadotrophin (FSH/LH) independent (i.e. primordial → primary → secondary is independent of FSH and LH, still don’t know exactly what triggers this, know some important cytokines and growth factors, but don’t know what triggers nor what keeps it quiescent)
→ starts to grow, very small surrounded by one singular layer of cells, oocyte diameter increasing to primary follicle, presence of zona pellucida at primary, outer cells cuboidal
• secondary: gonadotrophin dependent
→ everything changes: granulosa cells dividing quite heavily, oocyte doesn’t increase too much in diameter, really the outer cells in the follicle
→ FSH and LH receptors now present on granulosa cells therefore able to react and respond
→ on way to tertiary structure things start to speed up
• tertiary: gonadotrophin dependent
→ presence of fluid filled atrium → fluid is secretions from granulosa cells and from blood vessels
→ granulosa cells have divided many more times, there’s a lot more of them
→ theca cells in the very outer layer
• graafian = large antral and preovulatory
→ whole lot of things that are going on
→ oocyte surrounded by zona pellucida, surrounded by granulosa cells
→ granulosa cells become specialised in nutrient and cross talk between themselves and the oocyte
→ granulosa cells further from the zona pellucida and surrounding the atrium producing oestrogens
→ outside of that you have a basement membrane
→ theca cells on outside

18
Q

What are preantral and antral follicles?

A

Follicles as described by structure: preantral is primordial to secondary (i.e. prior to formation of atrium) while antral is tertiary and graafian follicle

19
Q

What is the time period of folliculogenesis?

A
  • Primordial to primary to secondary = months
  • secondary to tertiary = weeks
  • tertiary to graafian to ovulation = days
20
Q

What are the primordial and primary follicles?

A
  • at birth fixed number of follicles that decrease over lifetime, until menopause (human)
  • at around about 4 months of gestation we have a peak number of follicles - 6 to 7 million primordial germ cells/follicles in her ovaries
  • even before she is born these numbers have decreased to ~1 million
  • (these numbers are very dependent on the individual, they can vary massively by millions or 100,000s)
  • by the time the female has reached puberty there are only 300,000
  • over lifetime of menstruating will ovulate roughly 400 - 500 eggs
  • ~1000 eggs present at menopause
  • primordial follicles tend to associate in what we call nests
  • primoridal follicles are the earliest stage of oogenesis. Oocyte + one flat layer of cells
  • oogonium approx 20µm diameter, arrested in meiotic prophase, then grow and become a primary follicle
  • primary - single squamous or cuboidal layer of granulosa cells surrounded by membrana propria (basement membrane)
  • what regulates onset of development is unclear (AMH, PTEN, cytokines e.g. GDF-9?)
21
Q

What are the secondary or preantral follicles?

A
  • oogonium expands
  • the zona pellucida, an acellular layer, forms around the oocyte (glucoproteins)
  • granulosa cells form stratified layers
  • membrane propria
  • theca layer forms around the follicle
  • stroma cells = rest of the ovary
  • theca differentiates (interna vascularised, as opposed to theca externa)
  • as the granulosa layer (avascular) proliferates clefts appear between the cells and fluid starts to accumulate
22
Q

What are tertiary or antral follicles?

A
  • mature primary oocyte 120-300µm diameter
  • central cavity (antrum) containing follicular fluid
  • oocyte surrounded by specialised granulosa cells - cumulus oophorus, specialised for providing nutrients and communicating with oocyte
  • zona pellucida has many small pathways/gap junctions that allow transport of molecules in and out
  • basement membrane (membrana propria) seperates granulosa and theca
  • granulosa further away produce a lot of oestrogen
  • blood vessels only in theca (helps to prepare uterus)
  • receptors for LH (theca) and FSH (granulosa)
  • oestrogen and inhibin secretion
23
Q

What is atresia?

A
  • fate of most antral follicles
  • group or “cohort” of follicles grow but only one becomes dominant and ovulates
  • granulosa and theca layers break down
  • hormone production stops
  • oocyte degenerates
  • follicle remnants reabsorbed
  • leukocytes invade granulosa and theca cells and break them down
24
Q

What is the corpus luteum?

A
  • follicle forms corpus luteum after ovulation
  • granulosa cells transform and proliferate
  • theca cells transform, migrate into core, and mingle with granulosa derived cells
  • production of progesterone
  • massive vascularisation and angiogenesis (tumour-like growth)
  • huge change
25
Q

What is the corpus albicans?

A
  • regressing CL
  • no progesterone
  • occurs if not needed i.e. not pregnant
26
Q

What is the oviduct?

A
  • convoluted tube
  • muscular wall
  • secretory epithelium
  • site of fertilisation
27
Q

What is the uterus?

A
  • myometrium: 2 layers of muscle (circular and longitudinal)
  • endometrium: secretory glands in stroma, site of implantation
  • luminal epithelium: columnar epithelium, secretory
28
Q

What is the cervix?

A
'the gatekeeper' 
• tough connective tissue stroma 
• epithelium secretes mucus 
• prevents bacteria etc from vagina entering uterus 
• regulates sperm passage 
• retains embryo during pregnancy
29
Q

What is the vagina?

A
  • muscular wall
  • squamous epithelium - keratinised
  • sensitive to oestrogens
30
Q

What is the external genetalia? (human)

A
  • labia highly variable morphology

* clitoris - ‘little hill’ erectile tissue, same embryological origin as the penis

31
Q

What are the ovarian hormones?

A
Steroids: 
• five major classes:
1. oestrogens (oestradiol 17beta, oestrone, oestriol) 
2. progestagens (progesterone) 
3. androgens (testosterone) 
4. glucocorticoids 
5. mineralocorticoids 
• Sex steroids = oestrogen, progesterone, testosterone 
• precursor = cholesterol (from diet) 

eicosanoids: prostaglandins (PG)
• several families of PG (E, F, H, I)
• PGF2alpha → luteolysis; uterine contractions
→ arachidonic acid → via cyclo-oxygenase (COX1, COX2) → prostaglandin H2 → via PGF synthase to prostraglandin F2alpha OR → via PGE synthase → prostaglandin E2 (PGE2)

peptide or protein hormones:
• relaxin → relaxes cervix at full term
• oxytocin → (from posterior pituitary) uterine contractions; let milk down
• inhibin → suppresses FSH, homo/heterodimeric structures

growth factors and cytokes:
• transforming growth factor beta (TGF-beta): family members include: GDF-9, BMP-15, Follistatin
• epidermal growth factor (EGF)
• insulin-like growth factor I and -II (IGFs): IGF system (factors, binding proteins, proteases)