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ERS > ERS23 Female Reproductive Cycle > Flashcards

ERS23 Female Reproductive Cycle Flashcards

1
Q

Meiosis

A

1 DNA replication + 2 divisions

  • Meiosis 1: separation of Homologous chromosomes
  • Meiosis 2: separation of Sister chromatids

4 phases:

  1. Prophase
    - Preleptotene: **DNA synthesis (double chromosome number to 92)
    - Leptotene: Nuclear size ↑, Chromosomes condense —> visible under microscope
    - Zygotene: **    Pairing of Homologous chromosomes at some point
    - Pachytene: Pairing process move along entire chromosome, shortening + thickening, ***Crossing-over —> allow genetic materials of homologous chromosomes to exchange —> unique genetic composition
    - Diplotene: formation of Chiasmata (site of crossing over) (chromosomes slightly apart but remain attached)
    - Diakinesis: shortening and thickening of chromosome
  2. Metaphase —> chromosomes alignment on metaphase plane, disappearance of nuclear membrane
  3. Anaphase —> separation of Homologous chromosomes
  4. Telophase —> formation of nuclear membrane of daughter cells

Meiosis 2:

  1. Metaphase
  2. Anaphase —> separation of Sister chromatids
  3. Telophase
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2
Q

Meiosis in ovary

A

Unique features:
- 2 interruptions
—> 1 after Diplotene 1 (Prophase 1): Chromosomes uncoil themselves to become thin again —> Dictyotene stage
—> 1 after Metaphase 2: Stage after ovulation

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3
Q

***Female primordial germ cells development

A

Female primordial germ cells (2C: 2 complement sets of chromosomes) derived from hindgut
—> Migrate to genital ridge
—> during migration + initial stage of ovarian development
—> Mitosis
—> germ cell number ↑
—> **Oogonia (2C) in ovaries
—> Oogonia undergo Meiosis (8-9 weeks, completed by 6 months)
—> **Primary oocyte (4C)
—> Arrest at Diplotene of Prophase 1
—> Growth of oocyte and follicle
—> Remain in ovarian follicle until puberty
—> **Follicular maturation: Follicle recruited for development in menstrual cycle
—> **Meiosis 1 resumed
—> Unequal cell division occurs in Meiosis of oocytes
—> 1 Large cell: Secondary oocyte (Mature egg: 2C) + 1 Small cell (1st polar body: residual body destined to degeneration)
—> Arrest again at Metaphase 2 upon **LH surge
—> Ovulation
—> Sperm entry and fertilisation
—> Resumption of Meiosis 2
—> large **Pronucleated oocyte (1C: Haploid) + ***2nd polar body

Note:
Prolonged Meiotic division ↑ chance of being affected by exogenous factors
—> ↑ chromosomal abnormalities with female age
—> Age-dependent ↑ in Trisomy 21 (Down syndrome), Trisomy 16, 18

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4
Q

Germ cell population in ovary

A

6 months:
Maximum no. of germ cells (7 million): ***ALL Oogonia becomes Primary oocyte

Time of birth:
1 million Primary oocyte in ovary (enough for use: 400 oocytes ovulated within female reproductive life)
—> Female germ cells in ovary die afterwards
—> Germ cell number ↓ with age
—> a few left after menopause

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5
Q

Summary of Oogenesis

A

Primordial germ cells: Mitosis (↑ number of PGC in ovaries)

Meiosis in female:

  • start before birth —> ceiling on number of germ cells
  • ends after fertilisation
  • arrests at Prophase 1, Metaphase 2
  • result in Unequal cell division (only 1 functional oocyte is produced after Meiosis)
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6
Q

Ovary

A

2 functions:

  1. Production of oocytes
  2. Hormone production (by ***Follicular cells surrounding oocytes)

Oocyte + Follicular cells —> Ovarian follicle (Basic functional unit of ovary)

Folliculogenesis:
Primordial follicle —> Developing follicle —> Mature follicle —> Ovulated follicle —> Corpus luteum

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7
Q

***Classification of Ovarian Follicle

A

4 types:

  1. Primordial (smallest)
    - single Primary oocyte surrounded by single layer of flattened Follicular cells
  2. Primary
    - **↑ Oocyte size
    - Oocyte surrounded by non-cellular layer **    Zona pellucida
    - proliferation of Follicular cells —> **multiple layers of Follicular cells surrounding oocyte
    - Follicular cells —> **    Granulosa cell + ***Theca cell
  3. Secondary
    - formation of **Antrum (fluid-filled cavity), **Cumulus cells
    - **differentiation of Follicular cells into different cell types —> **produce Hormones
  4. Tertiary / Graafian (largest)
    - **resumption of Meiosis 1
    - ↑ size of follicles (∵ **    ↑ Antrum size)
    - Follicle bulge out just before ovulation at surface of ovary at a point—> Stigma
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8
Q

Structure of Primordial follicle

A
  1. Follicular cells (single layer) —> surround oocyte
  2. Basal lamina (最出)
  3. Primary oocyte
    - Nucleus (Dictyotene)
    - Nucleolus
    - Cytoplasm of Follicle
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9
Q

***Follicular development

A
  1. Preantral phase (Primary follicle):
    - **Independent of Gonadotropin
    - Growth of follicle mainly due to **    ↑ Primary oocyte size
    - Zona pellucida: non-cellular layer by Primary oocyte
    - Granulosa cell + Theca cell (differentiated from Follicular cells)
    - Granulosa cell: **Estrogen + **FSH receptors development
    - Theca cell: **LH receptors development
    —> by the end Follicle able to **    respond to stimulation by Gonadotropins
  2. Antral phase (Secondary follicle):
    - **Dependent on Gonadotropin
    - Growth mainly in **    Follicular cells + **Antrum
    - Granulosa cell + Theca cell —> **    produce Estrogen + Androgen respectively
    2 phenomena:
    - Two-cells theory for Estrogen production
    - Positive feedback of Estrogen production
    - **Sustained FSH presence and high Estrogen
    —> development of **    LH receptor in Follicle
  3. Preovulatory phase (Tertiary / Graafian follicle):
    - **Dependent on LH surge —> **completion of Meiosis 1 —> **Secondary oocyte + 1st polar body
    - **    Meiosis 2 arrested at Metaphase 2
    - Large ↑ in Antrum size
    - **Progesterone production (由分泌Estrogen變左分泌Progesterone) by Granulosa cells a few hours after LH peak
    - **    Granulosa cells —> differentiated into **Corona radiata cells + **Cumulus cells —> surrounds oocyte and ovulated together with oocyte
    - Cumulus cells: ovulated
    - Corona radiata: specialised type of Cumulus cells around oocyte which gets ovulated
  4. Ovulation
    - Formation of Stigma (site on ovarian surface where Graafian follicle burst out)
    - ↑ production of **Follicular fluid
    - ↑ production of **    Prostaglandins + **Proteolytic enzymes (to rupture follicle membrane)
    - Rupture of follicle membrane
    - **    Oxytocin —> contraction of Follicular membrane —> push Secondary oocyte + Cumulus cell out of ovaries
    - Secondary oocyte + Cumulus oophorus cells ovulated
  5. Luteal phase
    - Vascularisation of Granulosa layer
    - Granulosa cells + Theca cells
    —> transformed into Endocrine producing cells
    —> Hypertrophy + Cell physiological changes
    —> **Luteinisation
    —> **    Corpus luteum (80% Granulosa, 20% Theca)
    —> **Estrogen + **Progesterone production
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10
Q

Growth of Follicle

A

Primary follicle:
- Main growth due to ↑ Oocyte size

Secondary Follicle:
- Main growth due to ↑ Follicle size (∵ formation of Antrum)

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11
Q

Structure of Primary follicle

A
  1. Primary oocyte
    - **Zona pellucida
    —> Granulosa cells send protrusions (microvilli) through Zona pellucida
    —> touch Oocyte membrane
    —> Interaction between Oocyte and Granulosa cells
    —> **    Granulosa cells regulate resumption of Meiosis 1 of oocytes
    - Nucleus (Dictyotene)
    - Nucleolus
    - Cytoplasm of Follicle
  2. Follicular cells
    - **Granulosa cells —> multiple layers —> Zona granulosa (surrounding primary oocytes)
    - **    Theca cells
  3. Basal lamina —> separate Granulosa cells / Theca cells
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12
Q

Structure of Secondary follicle

A
  1. ***Antrum (fluid-filled cavity in follicle)
    - allow clinicians to observe growth of follicles by ultrasound
  2. Follicular cells
    - **Granulosa cells —> Endocrine cells (produce hormones)
    - **    Theca interna cells —> Endocrine cells (produce hormones)
    - Theca extena cells —> Fibroblast-like
    - Presence of blood vessels within Theca layer
  3. Primary oocyte
    - Zona pellucida
    - Nucleus
    - Nucleolus
    - Cytoplasm of Follicle
  4. Basal lamina
    - Separate Granulosa cells / Theca interna cells
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13
Q

***Two-cells theory for Estrogen production in Secondary follicle

A 
***LH receptor present in ***Theca cells
LH bind to LH-R
—> cAMP
—> Androstenedione / ***Androgens (from cholesterol)
—> diffuse through basal lamina
—> becomes substrate for Granulosa cells

**FSH receptor present in **Granulosa cells
FSH bind to FSH-R
—> cAMP
—> stimulate Aromatase
—> convert Androstenedione to Estrogen
—> **Estrogen production
—> transported into bloodstream / go into Follicular fluid / act on Granulosa cells (∵ possess Estrogen receptor)
—> **stimulate Granulosa cells to proliferate more + enhance production of Estrogen receptors
—> +ve feedback

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14
Q

***Fate of Corpus luteum

A

No fertilisation
—> Luteolysis (Corpus luteum die) (10-12 days after ovulation)
—> Corpus albicans (regressed Corpus luteum)
—> ↓ production of Estrogen + Progesterone
—> allow next cohort of follicles to develop

Fertilisation
—> formation of embryo + placenta
—> Blastocyst stage
—> **Blastocyst produce HCG (Human chorionic gonadotropin) (also by placenta in first 3 months of gestations)
—> HCG function ~ LH
—> continues to “luteinise” Corpus luteum
—> **allow Corpus luteum to continue produce Estrogen + Progesterone
—> until Placenta itself can produce Estrogen + Progesterone
—> maintain lifespan of Corpus luteum for ***3 months after pregnancy
—> Luteolysis (Corpus luteum die) after 3 months
—> Corpus albicans (regressed Corpus luteum)

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15
Q

Reproductive cycle in females

A
  1. Follicular phase: 7-23 days
  2. Periovulatory period: 1-3 days
  3. Luteal phase: 14 days (relatively constant) —> important to estimate time of ovulation when day of menstruation is known

Total: 21-35 days (average 28 days)

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16
Q

Hormones in female reproduction

A
  1. GnRH (Hypothalamus)
  2. FSH, LH (Pituitary)
    —> FSH: Maturation of follicles + LH-R expression
    —> LH: Corpus luteum formation + Ovulation
  3. Estradiol, Progesterone (Ovaries)
    —> Estradiol: from Follicles, Corpus luteum
    —> Progesterone: from Corpus luteum
    —> -ve feedback to pituitary
17
Q

***Hormonal pattern in female reproductive cycle

A

Day of menses: Day 1

Initial phase:
- FSH high (stimulate ↑ follicle size —> high Estrogen level)
—> ↓ with development
—> -ve feedback by Estrogen on Hypothalamus + Pituitary (only require **Low level of E2, Rapid onset)
- Estrogen ↑ (stimulate FSH, LH synthesis but **inhibit secretion —> accumulation of FSH, LH in pituitary)

Day 11-14 (Preovulatory phase):
- FSH ↑
—> High estrogen level become **stimulatory to synthesis + secretion —> +ve feedback —> FSH surge (一野爆出黎)
- LH ↑
—> High estrogen level become **stimulatory to synthesis + secretion —> +ve feedback —> ***LH surge (一野爆出黎) —> Ovulation + Corpus luteum
—> Luteinisation of Granulosa cells to produce Low level of Progesterone (a few hrs after LH surge) (Luteinisation starts before ovulation) —> ↑ pituitary sensitivity to GnRH
- Estrogen ↑ (2-3 days: induce ovulation + Luteinisation of Granulosa/Theca cells of follicular wall to become Corpus luteum)

After Day 14 (Luteal phase, formation of Corpus luteum —> Estrogen + Progesterone —> -ve feedback to FSH, LH, GnRH):

  • FSH low
  • LH low
  • Estrogen high
  • Progesterone high

Late Luteal phase (no fertilisation —> degeneration of Corpus luteum):

  • FSH ↑ —> stimulate growth of next cohort of follicles
  • Estrogen ↓
  • Progesterone ↓
18
Q

Follicular phase summary

A 
GnRH ↑ FSH/LH release
—> FSH ↑ growth of follicles
—> Granulosa + Thecal cells produce Estrogen (↑ Estrogen)
—> Estrogen -ve feedback:
1. ↓ FSH/LH release from pituitary
2. ↓ GnRH release from Hypothalamus
3. ***↑ FSH/LH synthesis
19
Q

Follicular maturation

A
  1. Recruitment phase (1-3 days)
    - a cohort of ***preantral follicles depart from resting pool and begin to grow (development of multiple follicles)
    - Preantral follicle not responsive to Gonadotropin —> can develop / undergo atresia
  2. Selection phase (5-11 days)
    - one member from cohort becomes Dominant follicle
    —> continue to develop to preovulatory follicles (mechanism unclear, maybe follicle with highest sensitivity to FSH)
    (Assisted reproduction treatment: give high dose FSH —> stimulate more follicle to develop)
  3. Dominance phase (13-15 days)
    - Dominant follicle ovulated eventually
    - other “un-ovulated” follicles die via Atresia (Atretic follicle)
20
Q

Ovulation phase summary

A

High estrogen for 2-3 days (***+ve feedback)

  • ↑ ***release and synthesis of FSH/LH
  • ↑ ***release of GnRH
  • ↑ pituitary sensitivity to GnRH

Low progesterone potentiates effect of Estrogen-induced LH surge
- ↑ pituitary sensitivity to GnRH

21
Q

Luteal phase summary

A

Early / Mid luteal phase (-ve feedback again)

  • High Estrogen + Progesterone ↓ GnRH release
  • ***High Progesterone blocks Estrogen actions

Late luteal phase
- Luteolysis —> Estrogen, Progesterone ↓ —> removal of inhibition —> FSH ↑

22
Q

Action of Estrogen from dominant follicle

A
  1. Inhibit growth of cohort follicles
  2. Enhance sperm transport through cervical mucus
  3. Enhance transport of ovum in oviduct
  4. Prime endometrial response for progesterone induced secretion (Prepare endometrium for implantation)
  5. Prime GnRH action on LH secretion for LH surge
23
Q

Action of Progesterone from Corpus luteum

A
  1. Ovulation (potentiates effect of Estrogen-induced LH surge)
  2. Uterine secretion in preparation for implantation (make endometrium more secretory)
  3. Development of embryo (stimulates Decidualization of endometrium to provide support for development of embryo)
24
Q

Endometrial changes during menstrual cycle

A
  1. Proliferative phase
    - Estrogen stimulate ***proliferation of endometrium (during Initial development of follicle)
    - early proliferative phase: only simple glandular endometrial glands
    - late proliferative phase: glands become bigger, start to see mitotic figures
  2. Secretory phase
    - after ovulation
    —> Progesterone from Corpus luteum stimulate **secretory events of uterine glands + **development of endometrium
    —> receptive to implanting embryo
    - early secretory phase: within glandular epithelium, can see vacuole-like structures at the base of glands (contains secretions of glandular epithelium —> released into glandular lumen)
    - late secretory phase: lumen become much bigger with secretions
25
Q

Basal body temperature changes

A
  • Determine ovulation
  • Increase in body temp after ovulation by Progesterone (slight delay)
    —> Egg already ovulated before rise in body temp (not accurate in contraception)
26
Q

Cervical mucus changes

A

Ferning:

  • Crystal formed by cervical mucus at time of ovulation
  • mucus to dry —> ferning
  • Estrogen action —> composition in cervical mucus changes

Score of ferning pattern:

  • ***high around ovulation (ferning —> fluid)
  • change in cervical mucus composition ***allow sperm to penetrate through mucus —> fluid instead of viscous
27
Q

Summary

A

Hormone:

  • FSH, LH changes
  • E2, P changes

Ovary:
- Follicular phase
(- Ovulation phase)
- Luteal phase

Follicle:

  • Preantral phase (85 days) (i.e. Primary follicle) (throughout reproductive cycle, ***Independent of Gonadotropin, follicle with high enough sensitivity to FSH develop into Antral phase)
  • Antral phase (8-12 days) (i.e. Secondary follicle)
  • Preovulatory phase (37 hrs) (i.e. Tertiary / Graafian follicle)
  • Corpus luteum phase (14 days)

Endometrium:

  • Proliferative phase
  • Secretory phase
28
Q

Detection of ovulation

A
  1. ***Menstrual cycles (if regular cycles)
  2. Basal body temperature (after ovulation, cannot be used to pinpoint exact time of ovulation)
  3. Urinary ***LH level (Ovulation specific, but difficult to catch 1/2 day of LH surge)
  4. Blood (***Progesterone level, only produced by Corpus luteum, occur after ovulation)
  5. Ultrasound (Development of antral follicle —> ***disappearance of Antral follicle —> indicate time of ovulation —> but require daily ultrasound)

ERS (41 decks)

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