Physiology Flashcards
What are the 3 levels of sexual dimorphism?
1) Genetic (M: XY, F: XX)
2) Gonadal (M: testes, F: ovaries)
3) Phenotypic
a) external genitalia
b) secondary sex characteristics
What gene encodes for the testis determining factor (TDF) and which chromosome is it located on?
SRY gene on Y chromosome
What is testis determining factor?
Nuclear transcription factor
- expressed in gonad immediately before divergence of ovarian/testicular development
- incites testis differentiation → formation of Sertoli and Leydig cells → produce MIS/Testosterone respectively
What is the key factor needed for the determination of male characteristics?
SRY/TDF
What are 5 genes that promote sexual differentiation in humans?
Male promoting:
1) SRY
2) SOX 9
Female promoting:
3) FOXL2
4) WNT4
5) FST
What essential hormone is produced by Leydig cells and what is its function?
Testosterone
- Wolffian duct development
What essential hormone is produced by Sertoli cells independent of FSH and what is its function?
Mullerian inhibiting substance/Anti-mullerian hormone (MIS)
- promotes Mullerian duct regression (to allow for Wolffian duct development)
What is Turner syndrome?
X0 chromosomal disorder
- F
- 1/2500
- Low IQ
- Infertile
- small stature
What is Klinefelter syndrome?
XXY chromosomal disorder
- M
- 1/700
- Low IQ
- Infertile
- Higher in stature
- Gynaecomastia/ small testes
What is hermaphroditism?
Having characteristics of both male and female
What is the difference between true hermaphroditism and pseudohermaphroditism?
True hermaphrodite:
- gonadal tissue and germ cells of both sexes present
- 50%: 1 testis/ovary + 1 ovotestis
- 30%: 1 testis + 1 ovary
- 20%: 2 ovotestes
Pseudohermaphrodite:
- inconsistency between internal and external genitalia
- 2 aetiologies:
i) Androgen insensitivity syndrom (AIS)/Testicular feminisation syndrome
ii) 5α-reductase deficiency
Describe the process of sexual differentiation in humans?
Male:
1) XY → SRY+
2) Testicular formation →
a) MIS → no mullerian duct → no uterus
b) Testosterone → (i) DHT (ii) Wolffian duct → Vas deferens, Epididymis, Seminal vesicles
3) DHT → Penis, Penile Urethra, Scrotum
Female:
1) XX/X0→ SRY-
2) Ovary formation →
a) No MIS → Mullerian duct → Uterus, Fallopian tube, Upper vagina
b) Estradiol → Clitoris, Labia minora/majora, Lower vagina
Describe the HPT axis in males.
Hypothalamus: GnRH
→ Anterior pituitary:
(i) LH → Leydig cells → Testosterone
- -ve feedback to AP and hypothalamus
(ii) FSH → Sertoli cells →
(i) Spermatogenesis
(ii) Androgen-binding protein w testosterone
(iii) inhibin
- -ve feedback to AP
Describe the function of GnRH.
Hypothalamus → GnRH → Gonadotrope cells in pituitary glands → FSH + LH
What are the hormones produced from the testes and which cells are they secreted from?
LH → Leydig cells → Testosterone
FSH → Sertoli cells →
i) Estradiol
ii) Inhibin
iii) Activin
iv) Follistatin
Inhibin and follistatin are secreted by ___________ and act to suppress _____ secretion.
Secreted by Sertoli cells under FSH stimulation
- act to suppress FSH secretion
- -ve feedback loop
What are 2 fates of plasma testosterone?
1) Estradiol (via aromatase in Sertoli cells)
2) DHT (via 5-α reductase)
3) Conjugated by liver
4) 17-Ketosteroids (via 17ß-dehydrogenase)
What are 6 functions of testosterone?
1) Control development of internal male genitalia
2) Support spermatogenesis
3) Support puberty
4) Support development of male secondary sex characteristics
5) Promote sex drive/libido (both M and F)
6) Promote protein synthesis and muscular growth
What is the enzyme responsible for DHT production?
5α-reductase
True or false. DHT is more potent than testosterone and thus its production is localised at specific target cells.
True
What are 3 effects of DHT?
1) Development of male external genitalia
2) Development and growth of prostate gland
3) Growth of male body/pubic hair (baldness)
What is the moa of DHT?
1) Testosterone diffuses across cell membrane
2) Testosterone converted to DHT by 5α-reductase
3) DHT binds to intracellular androgen receptor
4) DHT-AR complex undergoes dimerisation and phosphorylation
5) New complex passes through nuclear membrane to act at androgen-response element + recruits coactivator (ARA70)
6) Transcription of proteins → testosterone/DHT effects
How long does spermatogenesis take?
65-70 days
Describe the process of spermatogenesis.
1) Proliferation (3-4wks)
- Spermatogonium → 1° spermatocytes
- mitosis
2) Growth (3-4wks)
- 1° spermatocytes → 2° → spermatids
- meiosis
3) Differentiation (3-4wks)
- spermatids → spermatozoon
- Spermiogenesis
4) Maturation
- Spermatozoon → Mature spermatozoa
- in epididymis
Where does the maturation of sperm cells take place?
Epididymis
Describe the structure of a matured sperm.
1) Head
- acrosome and nucleus
2) Neck
3) Midpiece
- mitochondria
4) Tail
What are 5 hormones that exert their effects of spermatogenesis?
1) Testosterone
- essential for growth of germinal testicular cells
2) LH
- stimulates testosterone secretion from Leydig cells
3) FSH
- needed for spermiogenesis (spermatids → matured sperm)
4) Estrogens
- essential for spermiogenesis
5) Growth hormones
- essential for controlling background metabolic functions of the testes
What is the usual age range for puberty in males?
10-12 years old
What are the 2 main physical changes during puberty?
1) Secondary sexual characteristics
2) Somatic growth
At puberty, the hypothalamus increases the _________ secretion leading to the eventual incipience of adult sexual life.
GnRH → FSH LH (by AP) → Testosterone (by Leydig cells)
What is the clinical criteria for infertility?
After a couple failed to conceive after 12 months of regular unprotected sexual intercourse.
1/3 due to male
1/3 due to female
1/3 due to both
In true hermaphroditism, what is the
(i) Genetic sex
(ii) Gonadal sex
(iii) Phenotypic sex
i) 46 XX, 46XY or 47XXY
ii) Both testes & ovaries
iii) Female
- ambiguous with both male and female features
What are 2 causes of pseudohermaphroditism?
1) 5-ARD
- l.o.f mutation in 5α-reductase gene
- similar but less severe phenotypes than AIS before puberty
- during and aft puberty → development of male sexual characteristics
2) AIS
- partial or complete l.o.f of androgen receptor
- may be (i) complete, (ii) partial, (iii) mild
What are the 3 levels of sexual dimorphism in px with CAIS (complete androgen insensitivity syndrome)?
1) Genetic: XY-male
2) Gonadal:
- hidden testes
- no ovaries
- no cervix or uterus
3) Phenotypic:
- normal breast
- normal lower vagina (no upper)
- infertile
- higher testosterone than males
What are 4 differences between 5-ARD and AIS?
5-ARD:
1) mutation of 5-ARD gene (non-functional enzyme)
2) External genitalia may include micropenis or hypospadia
3) Male internal genitalia present (have Wolffian structures)
4) Develops male 2° sexual characteristic during puberty
AIS:
1) mutation of androgen receptor gene (non-functional receptor)
2) only female external genitalia
3) neither Wolffian nor Mullerian structures
4) Normal female 2° sexual characteristics
What are 4 similarities between 5-ARD and AIS?
1) XY
2) Testes present
3) Infertile
4) Primary amenorrhea
What is Kallmann syndrome?
Cause of hypogonadotropic hypogonadism
- mutation of more than 25 genes leading to failure in GnRH function
Kallmann syndrome:
Symptoms:________________
Diagnosis:_______________
Treatment:_______________
Kallmann syndrome:
Symptoms:
i) no/slow puberty, poor 2° sexual characteristics
ii) hypogonadism (low level of sex hormones)
iii) Infertile
iv) occurring both in M and F
Diagnosis:
i) Delay or no puberty
ii) low level of testosterone/estrogen and LH and FSH
Treatment: Hormone replacement (GnRH)
How is Kallmann syndrome differentiated from Klinefelter or Turner syndrome?
LH/FSH levels
Kallmann: ↓
Klinefelter/Turner: ↑ (no problem with hypothalamus + no -ve feedback from testosterone/estrogen)
True or false: There is a reduction in oocyte number from birth till menopause.
True
- 1 mil primary oocyte @ birth
- 200k primary oocyte @ puberty
- only 400 oocytes ovulated during entire reproductive years
All primary oocytes remain arrested at which stage of the cell cycle?
Prophase of Meiosis I
What is the main hormone controlling folliculogenesis?
FSH
What are 6 differences between spermatogenesis and oogenesis?
1) Cell cycle
- M: from interphase of mitosis + both mitosis and meiosis
- F: from P1 of meiosis + only meiosis
2) Meiosis
- M: full meiosis I and II
- F: starts @ P1 of meiosis and stops @ M2 of meiosis
3) Output
- M: 1 1° → 4 spermatozoa
-F: 1 1° → 1 oocyte
4) Length
- M: 7wks
- F: 13-50years
5) Duration
- M: puberty till death
- F: birth to menopause
6) Quantity
- M: millions/billions at a time
- F: 1 oocyte/month
What stage of the cell cycle is a primary oocyte in a primary follicle?
Arrested at P1
What stage of the cell cycle is a ovulated secondary oocyte?
Arrested at M2
Describe the process of folliculogenesis.
1) Primordial follicle
- oocyte + granulosa cells
2) Primary follicle
3) Formation of zona pellucida
4) Secondary follicle
- formation of fluid filled vesicles
- theca interna and externa
5) Mature/Graafian follicle
- Formation of antrum and cumulus mass
6) Ovulation
- oocytes released with zona pellucida and outer corona radiata
- granulosa cells converted to corpus luteum cells
7) Corpus luteum
- produce progesterone
8) Corpus albicans
What are the hormones produced from the ovaries and which cells are they secreted from?
LH → Theca cell → Testosterone
LH → Granulosa cell → Progesterone
FSH → Granulosa cell → Estradiol
What is the most reactive estrogen?
Estradiol (E2)
What are 6 functions of estrogens?
1) Control development of female external genitalia
2) Control folliculogenesis
3) Support puberty
4) Promote female secondary sex characteristics
5) Promote libido/sex drive
6) Promote metabolism (lipid synthesis)
7) Control menstrual cycle
What are 2 physiological sources of progesterone?
1) Ovaries (Granulosa cells in follicle and corpus luteum)
2) Placenta (during pregnancy)
What are 3 functions of progesterone?
1) Converts endometrium into secretory stage for implantation
2) Reduce the maternal immune response
3) Decrease contractility of uterine smooth muscle
What are 5 differences between estrogen and progesterone?
1) Source
- E: placenta @ late stage
- P: placenta @ early stage
2) 2º sex characteristics:
- E: development
- P: maintain
3) Endometrium:
- E: Proliferation
- P: converts to secretory stage to prepare implantation
4) Metabolism:
- E: Anabolic
- P: Catabolic
5) Timing:
- E: Before ovulation
- P: After ovulation
6) Libido
- E: ↑
- P: ↓
7) Cancer risk
- E: ↑
- P: ↓
Where is a mature ovum released from?
Graafian follicle
What is ovulation is stimulated by?
Sudden increase of LH in the middle of menstrual cycle
How many oocytes are released during ovulation physiologically?
1
What does the corpus luteum secrete?
Progesterone and estrogen?
What are the 3 phases of the ovarian cycle?
1) Follicular (growing follicle → ↑estradiol)
2) Ovulation (release of ovum after spike in LH and FSH)
- drop in estradiol
- rise in basal body temp
3) Luteal (Formation of corpus luteum → ↑progesterone, estrogen)
- degradation of corpus luteum to corpus albicans if not fertilised
What are the 3 phases of the uterine cycle?
1) Menses (Shedding of endometrium)
2) Proliferative (Thickening of endometrium by estradiol)
3) Secretory (glycogen and glycoproteins secreted from endometrium under LH)
When does puberty usually occur in females?
9-12 years
What is menarche?
Onset of menstrual cycle
What is thelarche?
Breast development
What are the hormonal changes in a female during puberty?
Hypothalamus → GnRH
→ AP → ↑FSH and LH + GH
→ ↑Estrogen
What is the difference between primary and secondary amenorrhea?
Primary: failure of onset of menstrual cycle by 16y/o
Secondary: absence of menstrual for 6mths
What are 4 possible causes of female infertility?
1) Genetic:
-eg. Turner syndrome (X0)
2) Developmental:
- Hypogonadotropism
- Hypogonadism
- Hyperprolactinemia
3) Environmental:
- Toxins
- Chemotherapy
The ovum lives up to _____________ after ovulation while sperm live up to_____________ in female genital tract.
Ovum: 12-24hrs
Sperm: 72hrs
Where does fertilisation usually occur?
Fallopian tube
What are 3 factors that facilitate the transport of sperm in the female reproductive tract?
1) Sperm motility
2) Contractions of uterus and oviduct
3) Chemical attraction to ovum
What is capacitation?
Activation of sperm for sperm to penetrate egg
- occurs after ejaculation in female genital tract
What is the acrosome reaction?
Redistribution of membrane constituents and ↑membrane fluidity and permeability when sperm binds to zona pellucida of egg
What are 2 changes to sperm that occur that facilitate fertilisation?
1) Capacitation
- ▲to sperm head for acrosome rxn
2) Acrosome rxn
- ↑membrane fluidity and permeability + redistribution of membrane constituents
What are the 3 changes to the ovum during/after fertilisation?
1) Cell membrane depolarises
- prevent membrane fusion w other sperm
2) Cortical/zona reaction
- inactivation of sperm receptor
- hardening of zona pellucida to impair subsequent sperm binding
3) Resumption of 2nd meiotic division
- start from M2 (was arrested)
Describe the fertilisation process after the sperm cell comes into contact with the ovum.
1) Acrosome rxn between sperm and egg
2) Contact between sperm and zona pellucida
3) Entry of sperm and contact w oolemma
4) Resumption of 2nd meiotic division (from M2)
5) Completion of meiosis
6) Formation of M and F pronuclei
7) Migration and union of M and F pronuclei
8) Zygote ready for 1st mitotic division
How can the estimated date of delivery be calculated?
1) 40 weeks from last mensus
2) Head to rump length → compare to chart
What are the 3 periods of prenatal development?
1) Pre-embryonic (1st 2 wks)
2) Embryonic (3-8wks)
3) Fetal period (9-38wks)
Describe the pre-embryonic stage of fetal development.
Day
0: fertilisation
1: 1st cleavage division → Blastomere (2cell)
2: 4 cell zygote
3: Early morula
4: Advanced morula
6: Blastocyst (inner cell mass + blastocoele w trophoblasts)
7-10: implantation
What are the components of a blastocyst?
1) Embryoblast (inner cell mass)
2) Blastocoele (blastocyst cavity)
3) Trophoblasts (lining)
Describe the process of implantation.
1) Blastocyst receptors bind to endometrium lining
2) Trophoblastic cells secrete enzymes to digest uterine cells
3) Endometrium thickens and becomes more vascularised
What is menopause?
End of female reproductive period
- due to depletion of oogenesis
- arnd 50y
- more fibrosed ovary w loss of dominant follicles
What are 3 effects of menopause other than infertility?
1) Osteoporosis
2) Atherosclerosis
3) Uterus/vagina atrophy
4) Breast atrophy
What are the changes to the pH and temperature as a sperm leaves the testes and enters the oviduct?
pH goes down then up by oviduct
Temp increases
Leaving testis: pH=7.4, 35°C
Epididymis: pH=6.5, 35°C
Seminal plasma: pH=6.9, 37°C
Oviduct/IVF: pH=7.4, 38.5°C
What are the 2 parts of the placenta?
1) Fetal part (chorionic plate)
2) Maternal part (decidua basalis)
What are 5 functions of the placenta?
1) Endocrine
- Estrogen, Progesterone
- Relaxin
- HCG
- hPL, hCS
2) Nutritional
- glucose, aa, FA, minerals, vitamin from maternal → fetal blood
3) Respiratory
- O2 from mother to fetus
- CO2 from fetus to mother
4) Immune
- Maternal Abs (esp IgG) → passive immunity to fetus
5) Excretory roles
- Nitrogenous waste from fetal blood to maternal blood
How late after ovulation does implantation usually occur?
7-10 days
What are the hormonal changes during pregnancy?
1) hCG rise to peak at 10weeks
- declines to basal level after 40weeks
2) Progesterone ↑ till delivery
3) Estrogen ↑ till delivery
4) Prolactin ↑ till delivery
Where is hCG produced?
By syncytiotrophoblasts in placenta
True or false: hCG can be detected immediately after fertilisation has occured.
False.
hCG produced by syncytiotrophoblasts in placenta AFTER implantation (6-8days)
hCG binds to __________ receptor on __________ to promote its function.
LH receptor on corpus luteum
What are 3 functions of hCG?
1) Maintain function of corpus luteum to secrete progesterone
2) Promote progesterone function by placenta
3) Promote testosterone production by fetus
4) Coordinate sexual differentiation of baby
What are 2 causes of a false negative urinary pregnancy test?
1) Too early
2) Too diluted
What are 2 causes of a false positive urinary pregnancy test?
1) Gestational trophoblastic disease (Hydatidiform mole)
2) Choriocarcinoma
How long after the last menstrual period would a urine pregnancy test be accurate?
30 days after LMP
What are 2 functions of a hCG urinary pregnancy test?
1) Early detection of pregnancy
2) Indicator of embryonic development
What are 3 changes to estrogen and progesterone production during pregnancy?
1) <8wks, both produced by corpus luteum, >8wks by trophoblasts in placenta
2) Both ↑ till delivery
3) Main estrogen during pregnancy E2 (Estradiol) → E3 (Estriol)
What are 3 functions of estrogen during pregnancy?
1) Promote growth of uterus and ↑uterine blood flow
2) Enhance function of progesterone and oxytocin
3) Enhance fetal development
4) Stimulate breast cell development and fat deposition
What are 3 functions of progesterone in pregnancy?
1) Support endometrium for nurturing the fetus
2) Inhibit myometrial contraction
3) Suppress maternal immunologic responses to fetal Ag
Human placental lactogen (hPL):
- produced by: ______________
- function: _______________
Human placental lactogen (hPL):
- produced by: placental syncytiotrophoblasts (same as hCG)
- function: support fetal nutrition
Prolactin (PRL):
- produced by: ______________
- function: _______________
Prolactin (PRL):
- produced by: Lactotrophs in Anterior Pituitary
- function: stimulate lactation
Relaxin:
- produced by: ______________
- function: _______________
Relaxin:
- produced by: corpus luteum of ovaries and placenta
- function: (i) soften cervix (ii) loosen connective tissues of pelvis
What are 4 maternal adaptations during pregnancy?
1) ↑ function
- Lung, CVS, Renal
2) Weight gain
3) Endocrine system:
- Sex hormones
- Thyroid hormones
4) Metabolism
- Fat deposition
- Insulin resistance
What are 3 sites of ectopic pregnancy and which is most common?
1) Tubal (95%)
2) Ovarian
3) Peritoneal
What are 4 causes of female infertility?
1) Anovulation
2) Endometriosis
3) Tubal disease
4) Fibroid
5) Gonadal failure
6) Luteal phase defect
7) Cervicitis
8) Antisperm Abs
9) Fertilisation/genetic issues
What are 3 causes of male infertility?
1) Varicocoele
2) Gonadal failure
3) Idiopathic oligo or azoospermia
4) Chemotherapy
5) Retrograde ejaculation
6) Genetic defects
Which part of the blastocyst do the embryological germ layers arise from?
Inner cell mass
What are the 3 stages of partuition?
1) Dilation
- dilation of cervix (3cm to 10cm) → effacement (thinning)
- duration: 8-10hrs (decreases w number of previous child births)
2) Fetal expulsion
- From when cervix is fully dilation to when baby is born
- duration varies
3) Delivery of placenta
- Fetal expulsion to delivery of placenta
- duration: 10-15mins
With increasing parity, the duration of the ______ stage of parturition decreases.
Dilation
What are 5 hormones involved in the control of parturition?
1) Progesterone
2) Estrogen
3) Prostaglandins
4) Oxytocin
5) Relaxin
What is the moa of progesterone in parturition?
1) Hyperpolarises myometrial cells → suppress uterine contractions
2) Inhibits Phospholipase A2 and thus subsequent prostaglandin synthesis
What is the moa of estrogen in parturition?
1) Depolarises myometrial cells → promotes uterine contractions
2) Promotes Phospholipase A2 and thus subsequent prostaglandin synthesis
During parturition, prostaglandins are produced by ____________________ due to the activation of PLA2 by ____________.
PE:
- produced by myometrium decidua and chorion (sharp ↑ before labor)
- by activation by estrogen
What is the moa of prostaglandins in parturition?
↑ Intracellular [Ca2+] to activate actin myosin →
1) Stimulate uterine contractions
2) Cause cervical ripening and dilation
True or false: Oxytocin is produced in the posterior pituitary gland.
False.
Oxytocin produced in Hypothalamus and STORED in posterior pituitary gland.
What type of receptors are oxytocin receptors and where are they expressed to facilitate parturition?
Cell surface GPCR
Expressed in both myometrium and endometrium
How does estrogen enhance oxytocin effects?
Increases expression of oxytocin GPCR receptors on uterine myometrium and endometrium
What are 4 functions of oxytocin?
1) Uterine contraction
2) Lactation
3) Social behaviour (love, sexual arousal, bonding, etc.)
4) Inflammation and wound healing
Relaxin is produced in _______________________ during pregnancy and bind to ________________ receptors found on _________________.
Relaxin:
- produced in (i) corpus luteum of ovary (ii) placenta during pregnancy
- bind to relaxin GPCR receptors expressed in smooth muscle
What is the moa of relaxin?
Bind to relaxin GPCR receptor LGR7 and LGR8 →
Pregnancy:
i) ↑CO
ii) ↑Renal blood flow
iii) ↑arterial compliance
Parturition:
i) ↑oxytocin receptor
ii) assist cervical ripening
iii) soften pubic symphysis
Describe the hormonal control of parturition.
1) Estradiol from placenta readies uterus for oxytocin response
2) Fetus head pushes against cervix → activates stretch receptors → send signals to hypothalamus
3) Hypothalamus stimulates secretion of oxytocin from posterior pituitary
4) Oxytocin stimulates stronger uterine contractions
5) Prostaglandins from uterus also enhance contractions
6) Enhanced contractions → ↑2-6 (+ve feedback until fetal expulsion)
Development of the the breast is mainly controlled by ________ during puberty, however, ________ converts epithelium into secretory cells.
Mainly controlled by estrogen
but progesterone converts epithelium into secretory cells
Which 3 hormones influence the development of the breast in pregnancy?
1) Estrogen
2) Progesterone
3) Prolactin
Estrogen and progesterone (promote/inhibit) milk secretion during pregnancy.
Inhibit
What is the physiological trigger for milk production in females?
Sudden reduction of estrogen and progesterone after birth.
What are the 2 main hormones that control lactation?
1) Prolactin
2) Oxytocin
- stimulates myoepithelial cells for milk ejection
Human milk has (more/less) fat and carbohydrates and thus (more/less calories) than cow milk.
More
(but less protein)
What are 4 functions of prolactin?
1) Lactation
2) Immunity
3) Haematopoiesis
4) Angiogenesis
What are 5 benefits of breastfeeding?
To mother:
1) ↓risk of breast and ovarian cancers
2) ↓risk of T2DM
3) ↓Stress and prevents postpartum depression
4) ↑bonding w child
5) ↑intervals between pregnancies
To baby:
1) Protection against infections (from Abs, hormones, digestive enzymes, etc.)
2) Brain development (eg. from LCFAs)
3) Sucking and swallowing motions may ↓risk of bacterial colonisation of tubes and promote craniofacial development
What are the 3 main effects of the lactation reflex in breastfeeding?
1) Maintain lactation
2) Promote release of prolactin and oxytocin for milk production and ejection
3) Suppression of gonadal function and ovulation
What is the WHO recommended period of breast feeding?
Exclusively breastfed for 6mths, can continue w other foods up to 2 years or beyond
Why is the possibility of pregnancy reduced when a woman is fully breastfeeding?
Lactational amenorrhoea:
1) Breastfeeding → lactation reflex → ↑prolactin
2) ↑prolactin inhibit GnRH (↓) → ↓oestrogen
3) ↓oestrogen → cannot surge to incite ovulation
What is the usual time period for lactational amenorrhoea?
If fully breastfeeding, 6mths after delivery
