ERS25 Puberty And Pregnancy Flashcards
Pregnancy
280 days (40 weeks) after last menstruation (2 weeks of ovulation) 266 days (38 weeks) after fertilisation (IVF treatment)
First week of life
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
Preimplantation embryo development
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)
8th day of development
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
9th day of development
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)
End of 3rd week of development
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
Development of placental villi
- Primary villi
- Syncytiotrophoblast (outside)
- Cytotrophoblast (inside) - Secondary villi
- Syncytiotrophoblast
- Cytotrophoblast
- Centre of villi —> ***Mesodermal core - 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
***Functions of Placenta
- Exchange of metabolic and gaseous products
—> function as fetal lung, gut, kidney
- O2, CO2
- Nutrients, Electrolytes
- Fluid volume regulation, waste disposal
- Maternal Ab - 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
Transport of O2 to fetus
- Haemoglobin O2 affinity:
Fetal > Maternal
—> allow fetal Hb to carry more O2 at same oxygen tension - 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)
Human Chorionic Gonadotropin
- ***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
- ***↑ Fetal Testosterone
- ***↑ Fetal adrenal DHEA-S (substrate of placental estrogen)
***Progesterone from Placenta
- Produced by ***Syncytiotrophoblast
- ***keep ↑ throughout pregnancy
Functions:
1. ↑ Oviductal, Uterine endometrial gland secretion
- ↑ Decidual cell development (from endometrial stromal cells) —> nutrient supply for embryo
- Uterine quiescence
- ↓ Uterus contractility
- ↓ Sensitivity to Oxytocin (↓ stimulation of uterine contraction)
- ↓ Prostaglandin production (avoiding expulsion of fetus in early pregnancy) - ↓ Immune response to fetus (local suppression of immune response of mother)
- ↑ Maternal ventilation
- Prepare breasts for lactation
***Estrogens from Placenta
- 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):
- Enlargement of uterus, female external genitalia
- Growth of breast ductal structure
- Pelvic ligaments + Pubis symphysis relaxation/softening (with Relaxin) during parturition
- ↑ Progesterone synthesis (by ↑ LDL cholesterol uptake)
Embryonic period + Fetal period
Development of baby in 2 periods:
- Embryonic period
- 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 ↓
***Maternal metabolism
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
Maternal physiology
- ↑ Food intake, weight gain
- ↑ CO, blood volume
- ↑ Ventilation
- ↑ Urine formation
—> ↑ nutrient, O2 supply, Remove metabolic wastes
Parturition
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
Initiation of Labour
- 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
***Estrogen and Progesterone ratio during Labour
Early pregnancy: Progesterone > Estrogen
—> then Progesterone level off, slightly ***↓ during parturition time
—> Estrogen continue to ↑
Late pregnancy: Estrogen > Progesterone
High Estrogen:Progesterone ratio
- Facilitate release of ***Oxytocin from pituitary —> stimulate myometrium to contract
- ***↑ Oxytocin receptor in myometrium —> more sensitive to Oxytocin
- ***↑ Prostaglandins synthesis + release
Oxytocin
- 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
Fetal role in Labour
- Mechanical stretch of uterine musculature
- Hormonal factor
- **Oxytocin (fetal pituitary)
- **Cortisol (fetal adrenal gland) —> ↑ Prostaglandins
- ***Prostaglandins (fetal amniotic + chorionic membrane) —> membrane rupture, cervical dilatation, myometrial contractility
3 stages of Labour
- ***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) -
**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) -
**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
Puberty
- 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
Mechanisms of puberty
- 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
- Gonadostatic hypothesis
Puberty due to:
- Changes in pituitary responsiveness to -ve feedback by Steroid
- 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]
- Hypothalamic maturation hypothesis
**Maturation of CNS
—> **↑ output of Hypothalamic GnRH
—> Puberty
Evidence:
- Young monkeys undergo puberty in pulsatile LH without gonads (not involve Steroid -ve feedback)
- Gonadotropin ↑ in agonadal (i.e. without Steroid influence) children (Turner’s syndrome) in expected time of puberty
- Demethylation of GnRH gene (i.e. ↑ gene expression) in GnRH neurons during embryonic development in vitro —> ↑ GnRH secretion
Hypothalamic control of puberty
- 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))
