ERS25 Puberty And Pregnancy Flashcards

1
Q

Pregnancy

A
280 days (40 weeks) after last menstruation (2 weeks of ovulation)
266 days (38 weeks) after fertilisation (IVF treatment)
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2
Q

First week of life

A

Follicles develop within ovaries before ovulation
—> Primordial follicles
—> Primary follicles
—> Secondary follicles
—> Tertiary follicles
—> Ovulation (Oocytes + Cumulus cells) + Corpus luteum (Granulosa + Theca cells)

Sexual intercourse, Sperm travels:
Vagina
—> Cervical canal
—> Uterine cavity
—> Fallopian tubes
—> Ampulla (fertilisation occurs)

Fertilised zygotes start to cleave
—> Embryo
—> leave Fallopian tube into Uterine cavity (by 1st week)
—> Blastocyst
—> if Endometrium is right / Receptive to implanting embryo
—> Embryo attach and penetrate into endometrium

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3
Q

Preimplantation embryo development

A

Day 0:
Sperm + Oocyte (arrest at Metaphase 2, sometimes immature oocyte at Metaphase 1, Prophase 1, collected 36 hours after induction of ovulation)

Day 1:
Fertilised zygote:
- 2 pronuclei (1 from sperm, 1 from oocyte)
- 2 polar bodies (1st polar body + 2nd polar body)

Day 2:
Zygote divide into 2 cells
—> 4 cell stage

Day 3:
6-8 cell stage

Day 4:

  • **Morula
  • can no longer count no. of cells in embryo (∵ tight junctions between cells of embryo —> compact together to form ball of cells)

Day 5:

  • **Blastocyst (2 cell types + fluid filled cavity)
    1. Trophectoderm (epithelium on outside of blastocyst —> develop into placenta) —> Trophoblast
    2. Inner cell mass (develop into fetus) —> Embryoblast
    3. Blastocoel (fluid filled cavity —> grow in size)

Day 6:
Blastocyst come out out Zona pellucida (degenerating) in order to implant (Hatching of Blastocyst)

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4
Q

8th day of development

A

Trophectoderm
—> Trophoblast (after implantation)
—> **Cytotrophoblast (inner mononuclear cell) + **Syncytiotrophoblast (outer multinucleated)
—> Cytotrophoblast migrate into and fuse with Syncytiotrophoblast

Inner cell mass
—> Embryoblast

Endometrial stroma
—> near implanting embryo becomes **oedematous + **vascularised
—> Endometrial stromal cell transformed into Decidual cells
—> **↑ size, abundant secretory granules, cytoplasmic accumulation of **glycogens + lipid droplets
—> provide nutrition for implanting Blastocyst

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5
Q

9th day of development

A

Blastocyst deeply embedded in Endometrium (成粒入左去, 唔係lung住)
—> surface of endometrium at implantation site closed by ***Fibrin coagulum

Syncytiotrophoblast
—> small vacuoles occur and fuse
—> ***Trophoblastic lacuna (for maternal blood)

Cytotrophoblast
—> proliferate + penetrate into Syncytiotrophoblast
—> ***primary stem villi (cellular columns of Cytotrophoblast covered by Syncytiotrophoblast) (for fetal blood)

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6
Q

End of 3rd week of development

A

Fetal blood vessel gradually formed inside **Cytotrophoblast villi
—> Tertiary stem villi (containing **
fetal blood)
—> ***Placental villi
—> ↑ area of exchange (↑ efficiency of process)

Syncytiotrophoblast invade into maternal blood vessel
—> ***maternal blood flows into Trophoblastic lacuna

Maternal blood / Fetal blood close to each other for ***exchange of nutrients, metabolic wastes

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7
Q

Development of placental villi

A
  1. Primary villi
    - Syncytiotrophoblast (outside)
    - Cytotrophoblast (inside)
  2. Secondary villi
    - Syncytiotrophoblast
    - Cytotrophoblast
    - Centre of villi —> ***Mesodermal core
  3. Tertiary villi
    - Syncytiotrophoblast
    - Mesodermal core: **Villous capillary system (with **fetal blood) formed within
Gradual removal of barriers between Materal (outside villi) / Fetal blood (within villi in mesodermal core):
4th week: 4 barriers
- Syncytiotrophoblast
- Cytotrophoblast
- Connective tissue
- Endothelium (Fetal blood)

4th month: 2 barriers

  • Syncytiotrophoblast
  • Endothelium (Fetal blood) (直接掂住 Syncytiotrophoblast)
  • 無左Cytotrophoblast + CT
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8
Q

***Functions of Placenta

A
  1. Exchange of metabolic and gaseous products
    —> function as fetal lung, gut, kidney
    - O2, CO2
    - Nutrients, Electrolytes
    - Fluid volume regulation, waste disposal
    - Maternal Ab
  2. Production of hormones (relationship like Hypothalamus/Pituitary)
    Cytotrophoblast (~ Hypothalamus)
    —> **Hypothalamic releasing / inhibitory like hormones e.g. CRH, TRH
    —> **
    Growth factors

Syncytiotrophoblast (~ Pituitary)
—> **Pituitary hormone like hormones e.g. **HCG (LH-like), **HCS (Human chorionic somatomammotropin), HPL (Human placental lactogen, GH-like)
—> **
Steroid e.g. Estrogen, Progesterone

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9
Q

Transport of O2 to fetus

A
  1. Haemoglobin O2 affinity:
    Fetal > Maternal
    —> allow fetal Hb to carry more O2 at same oxygen tension
  2. Hb concentration is also higher in fetus

O2 dissociation curve:
Fetal curve on ***left of Maternal curve (same PO2, higher % saturation)

Bohr effect:
↑ [CO2], ↑ Temp, ↓ pH
—> O2 dissociation curve shifts to right
—> ↓ O2 affinity

Example:
CO2 diffuse from fetal to maternal blood in placenta
1. ↓ O2 affinity of maternal Hb —> release O2 —> diffuse into fetal blood
2. ↑ O2 affinity of fetal Hb (∵ less CO2)

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10
Q

Human Chorionic Gonadotropin

A
  • ***Specific for placenta —> detection of pregnancy
  • Produced by **Embryo + **Syncytiotrophoblast (after implantation, production ↑ in first 12 weeks)
  • from 8-9 days after ovulation, peaks in 12 weeks —> ↓ afterwards

Functions ~ LH:
1. **Maintain Corpus luteum
—> ↑ steroids (Estrogen + Progesterone)
—> ↑ relaxin
—> **
allow Corpus luteum to continue produce Estrogen + Progesterone
—> until Placenta itself can produce Estrogen + Progesterone

  1. ***↑ Fetal Testosterone
  2. ***↑ Fetal adrenal DHEA-S (substrate of placental estrogen)
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11
Q

***Progesterone from Placenta

A
  • Produced by ***Syncytiotrophoblast
  • ***keep ↑ throughout pregnancy

Functions:
1. ↑ Oviductal, Uterine endometrial gland secretion

  1. ↑ Decidual cell development (from endometrial stromal cells) —> nutrient supply for embryo
  2. Uterine quiescence
    - ↓ Uterus contractility
    - ↓ Sensitivity to Oxytocin (↓ stimulation of uterine contraction)
    - ↓ Prostaglandin production (avoiding expulsion of fetus in early pregnancy)
  3. ↓ Immune response to fetus (local suppression of immune response of mother)
  4. ↑ Maternal ventilation
  5. Prepare breasts for lactation
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12
Q

***Estrogens from Placenta

A
  • Produced from ***Syncytiotrophoblast
  • mainly ***Estriol (3 OH group —> different from that by Corpus luteum: Estradiol: 2 OH group)
  • Lower potency than Estradiol
  • Much higher amount produced (vs small amount of Estradiol)
  • ***keep ↑ throughout pregnancy

Functions (stimulate growth):

  1. Enlargement of uterus, female external genitalia
  2. Growth of breast ductal structure
  3. Pelvic ligaments + Pubis symphysis relaxation/softening (with Relaxin) during parturition
  4. ↑ Progesterone synthesis (by ↑ LDL cholesterol uptake)
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13
Q

Embryonic period + Fetal period

A

Development of baby in 2 periods:

  1. Embryonic period
  2. Fetal period

Embryonic period:
- **1-8 week
- **
Differentiation period
- 3 germ layer establishment (Ectoderm, Mesoderm, Endoderm)
—> formation of tissues and organs
- Shape of embryo changes greatly as a result of formation of organ systems
- 4th week: Pharyngeal arches, Heart bulge, Somites
- 7th-8th week (human-like): Ear, Eye, Toe

Fetal period:

  • 3rd month onwards
  • ***Maturation period
  • Maturation and growth of tissues, organs, body
  • ***Fewer malformation arise during this period
  • Head:Trunk ratio ↓
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14
Q

***Maternal metabolism

A

1st phase: Anabolic phase (early stage of pregnancy, insignificant nutrient requirement from fetus)
Overall: ***↑ Genesis —> ↑ Maternal reserve for future fetal development
- ↑ insulin sensitivity
- ↑ lipogenesis, ↓ lipolysis
- ↑ protein synthesis —> growth of breast, uterus, musculature for pregnancy and labour
- ↑ glycogen store in liver / muscle
- normal / low plasma levels of glucose, a.a., fatty acids

2nd phase: Catabolic phase (accelerated starvation of mother, to ↑ nutrient supply for accelerated weight gain of fetus during growth period)
Overall: ***↑ Lysis, ↓ Genesis —> ↑ Nutrient supply to fetus
- insulin resistant (placental HCS)
- ↓ lipogenesis, ↑ lipolysis
- ↓ protein synthesis
- ↓ glycogenesis
- ↑ plasma levels of glucose, a.a., fatty acids

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15
Q

Maternal physiology

A
  1. ↑ Food intake, weight gain
  2. ↑ CO, blood volume
  3. ↑ Ventilation
  4. ↑ Urine formation
    —> ↑ nutrient, O2 supply, Remove metabolic wastes
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16
Q

Parturition

A

Fetus, Placenta, Membranes are expelled from Uterus through birth canal

Expulsion of baby involved
1. Rhythmic contraction of uterus
2. Ripening of cervix
—> softer and easily dilatable

17
Q

Initiation of Labour

A
  • Mechanism not completely known
  • High redundancy
    —> no single trigger for initiation
    —> involve multiple mechanisms involving Maternal and Fetal components
  • Once triggered —> +ve feedback of cascade of events —> ensure Parturition go to completion
18
Q

***Estrogen and Progesterone ratio during Labour

A

Early pregnancy: Progesterone > Estrogen
—> then Progesterone level off, slightly ***↓ during parturition time
—> Estrogen continue to ↑

Late pregnancy: Estrogen > Progesterone

High Estrogen:Progesterone ratio

  1. Facilitate release of ***Oxytocin from pituitary —> stimulate myometrium to contract
  2. ***↑ Oxytocin receptor in myometrium —> more sensitive to Oxytocin
  3. ***↑ Prostaglandins synthesis + release
19
Q

Oxytocin

A
  • Produced by Hypothalamus
  • Released from Posterior pituitary
  • Neuroendocrine +ve feedback mechanism in parturition
Fetus grow in size, Tactile stimulation of reproductive tract (esp. Cervix)
—> stretch cervical muscle
—> neural signal through spinal cord to brainstem
—> stimulate hypothalamus
—> pituitary release Oxytocin into blood
—> arrive at Myometrium
—> Myometrium contraction
—> push fetus outward
—> stretch cervix even more
—> more Oxytocin release

Release of Oxytocin also enhanced by high Estrogen: Progesterone ratio

Oxytocin also ↑ Prostaglandins synthesis + release

20
Q

Fetal role in Labour

A
  1. Mechanical stretch of uterine musculature
  2. Hormonal factor
    - **Oxytocin (fetal pituitary)
    - **
    Cortisol (fetal adrenal gland) —> ↑ Prostaglandins
    - ***Prostaglandins (fetal amniotic + chorionic membrane) —> membrane rupture, cervical dilatation, myometrial contractility
21
Q

3 stages of Labour

A
  1. ***Dilation stage
    - regular uterine contractions from fundus —> widening of cervix —> ends with fully dilation of cervix
    - shorter duration in 2nd pregnancy (Multigravidas) (6-8 hrs, 1st pregnancy (Primigravidas): 10-12 hrs)
  2. **Expulsion stage
    - begins with fully dilated cervix —> ends when fetus forced out of uterus through cervix by coordinated contraction of:
    —> **
    Uterine muscle
    —> **Abdominal wall + Diaphragm voluntary muscles
    - Uterine contraction initiates on one end —> gradually spread to cervical canal
    - Intensity of contraction —> **
    cyclical pattern
    - shorter duration in 2nd pregnancy (Multigravidas) (15-30 mins, 1st pregnancy (Primigravidas): 1 hr)
  3. **Placental stage
    - begins after birth of child
    - ends with:
    —> Separation of placenta from Decidual tissues of uterus
    —> Expulsion of placenta + membranes
    —> Myometrial contractions —> **
    blood vessels constriction, prevent excessive bleeding
    - duration: 10 mins
22
Q

Puberty

A
  • Transition from non-reproductive to reproductive state
  • Physiological + Morphological + Behavioural changes
  • Time of puberty genetically determined

Growth velocity curve in boys / girls:
Girls have earlier growth spurt than Boys

Chronologic events in puberty
Girl:
- ***FSH ↑ before LH ↑ (then cyclical profile)
- Breast budding 1st physical sign of puberty —> development start with Estradiol ↑ from Ovarian follicles (result of FSH stimulation)
- Menses occur ~2 years later when LH ↑

Boy:

  • Enlargement of testes 1st physical sign of puberty —> associated with ↑ FSH, ↑ LH (***一齊上)
  • LH stimulate Leydig cells —> Testosterone ↑ —> Penis growth
23
Q

Mechanisms of puberty

A
  • Unclear
  • ***↑ Pulsatile LH release —> initiation of puberty
  • ***Amplitude of LH pulses ↑ at night during juvenile-early puberty transition

Peripubertal period:
- Preovulatory LH surge via +ve feedback of Estradiol
—> marks maturation of Hypothalamus-pituitary-ovarian unit in girls
—> sign of puberty

Fetus produces Gonadotropins and Steroids
—> Hormone production machinery is already available before puberty during neonates (serum levels may even > puberty)
—> ↓ activity of Hypothalamic-pituitary-gonadal axis after birth
—> production restrained before puberty

2 Hypotheses for Pituitary-gonadal activation
1. Gonadostatic hypothesis
2. Hypothalamic maturation hypothesis
—> NOT mutually exclusive

24
Q
  1. Gonadostatic hypothesis
A

Puberty due to:

  1. Changes in pituitary responsiveness to -ve feedback by Steroid
  2. Steroid-mediated changes in pituitary responsiveness to GnRH
  • Low threshold for -ve feedback regulation of pituitary FSH/LH secretion by Steroids
    —> sensitive to low levels of steroids
    —> Gonadotropin secretion easily inhibited
  • **Threshold increase at puberty
    —> pituitary **
    less sensitive to steroids
    —> less -ve feedback
    —> ↑ [Gonadotropin] + [Steroids]
25
Q
  1. Hypothalamic maturation hypothesis
A

**Maturation of CNS
—> **
↑ output of Hypothalamic GnRH
—> Puberty

Evidence:

  1. Young monkeys undergo puberty in pulsatile LH without gonads (not involve Steroid -ve feedback)
  2. Gonadotropin ↑ in agonadal (i.e. without Steroid influence) children (Turner’s syndrome) in expected time of puberty
  3. Demethylation of GnRH gene (i.e. ↑ gene expression) in GnRH neurons during embryonic development in vitro —> ↑ GnRH secretion
26
Q

Hypothalamic control of puberty

A
  • Initiation of puberty requires coordinated activities of gene networks
  • ↑ excitatory inputs + ↓ inhibitory inputs —> pubertal activation of GnRH Pulsatile release from Hypothalamus —> ***↑ LH pulsatility (endocrine manifestation of puberty)
  • involve ***Epigenetic modification of genes (e.g. Demethylation)
  • Environmental factors (e.g. nutrition, endocrine disruptors) affect these genes and pubertal development
(Hypothalamus:
Preovulatory GnRH surge
- ↑ Excitatory neurons (Kisspeptin, Glu)
- ↓ Inhibitory neurons (GABA, Opioids)
- ↑ Glial cells (Astrocytes)

GnRH pulsatility

  • ↑ Excitatory neurons (KNDy, Glu)
  • ↓ Inhibitory neurons (GABA, Opioids)
  • ↑ Glial cells (Astrocytes))