Physiology Flashcards
2 functions of gonads
- endocrine
2. gametogenic
Role of SRY in males
SRY > SOX9 > Other genes > sertoli cells > leydig cells/testes > hormones > male ducts and genitals
What is the biopotential gonad?
Embyro - bipotential genital ridge has both Wolffian and Mullerian ducts
What happens to the Wolffian and Mullerian ducts in males and females?
Male:
• Mullerian ducts regress (apoptosis)
• Wolffian ducts differentiate epididymis + vas deferens
Female:
• Wolffian ducts regress – apoptosis
Mullerian ducts differentiate oviducts, fallopian tubes, uterus, cervix and upper vagina
At what point in parturition are the reproductive axes differentiable?
7 weeks
7-8 weeks: primitive gonad cortex development = SRY activation
Males: SRY controls early testes differentiation and stimulates sertoli and leydig cells to secrete Testosterone and AMH
Females: primitive gonad cortex develops into ovary (medulla regresses) and the embryonic ovary does not secrete hormones
How is puberty regulated by the HPG axis?
Brain stimulates the hypothalamus > increase GnRH Ant pit. > increase LH + FSH > gonads to produce sex hormones > ovaries produce estrogens and testis produce testosterone
Pulsatile secretion of GnRH
- Onset of GnRH pulses typically occurs at night, due I part to gradual decrease in nocturnal melatonin secretion from pineal gland
- Also influenced by nutritional status of body and growth rate (Leptin/ghrelin, GH + IGF-1)
What converts testosterone to DHT in target cells?
5 alpha reductase
What complexes are required for male external genitalia?
DHT-R complexes
Testosterone feedback control
- Systemic T powerfully inhibits GnRH +LH secretion ( reduced testosterone)
- Blood testis barrier – sertoli
- Leydig cells secrete T bathes seminiferous epithelium, provides 100x increase in local androgen
- Sertoli cells also secrete ABP
**IV testosterone does not raise testes androgen level much so = reduced sperm count
Temperature difference and regulation between body and testes
- Temperature in testes is 2-3’C lower than body temperature
- Scrotum > sweat glands, pampiniform plexus, cremaster + dartos muscle (increase temp cremaster m dartos relaxes > testes descend > cool)
- Pampiniform plexus CCX
Spermatogenesis steps
- primordial germ cells (embryonic) migrate become spermatogonia
- @puberty, spermatogonia mature, proliferate and differentiate»_space; 1° spermatocyte
- Meiosis I»_space; 2x 2 spermatocytes
- Meiosis II»_space; 4x spermatids
- Differentiate into mature spermatozoa
- 1 spermatogonium can»_space; ~512 sperm, takes ~74 days
4 functions of sertoli cells
- Envelope/create niche/nourish germs cells (lose
contact = die) – contain lipid, glycogen - Secretory: AMH, inhibins/activins, ABP, oestradiol
- Create blood-testis barrier (apical sp. movement reqs constant reforming of gap junctions)
- Modify seminiferous tubule fluid (↑ local [steroid], [nutrients])
Contents of head and tail of spermatozoa
Head
¥ Contain haploid genome – X or Y
¥ Acrosome: large quantities of hyaluronidase and proteolytic enzymes to facilitate ovum penetration
¥ Minimal cytoplasm
Tail
¥ Mitochondria-packed»_space; power
¥ Motile microtubules flagellate – propels sperm @ 1-3mm/min
Sperm maturation
Achieved at distal corpus or caudal (6-8 days)
- Acquire progressive motility
- Biochemical changes
o ↑ capacity for glycolysis
o ↑ phospholipid & phospholipid-like fatty acid content
o Activation of CatSper (Ca2+-R reqd for acrosome rxn)
o Olfactory Rs»_space; chemotaxis (lily of the valley)
Vascular event of erection
Parasympathetic
Vasodilation: increased arterial blood flow to corpora cavernosa turgor compresses veins = limits loss of blood erection
Ejaculation
Sympathetic - 2 part spinal reflex
Emission
o Movement of semen through urethra
o Vas deferens sm. Muscle contraction move sperm forward
o Prostate, seminal vesicle sm muscle contraction move prostatic + seminal fluid forward
Ejaculation
o Propulsion, expulsion
o Rhythmical contraction of bulbospongiosus
Capacitation
PSA degrades semenogelin»_space; increase motility, alkaline uterine/fallopian fluid alters membrane (reduces chol, increases Ca2+ perm)
Acrosome reaction
- Hyaluronidase and proteolytic enzymes digest proteins in ovum ECM
- Sperm reaches zona pellucida»_space; sperm membrane binds receptor proteins (ZP3), entire acrosome rapidly dissolves enzyme release
- Open penetrating pathway for passage of the sperm head through the zona pellucida»_space; inside ovum.
- Sperm head + oocyte membranes fuse (cortical rxn) »_space;deliver sperm genome
Endocrine function of the ovaries
Oestrogens (potency: beta-estradiol > oestrone > oestriol)
o Granulosa cells - also corpus luteum
o Require aromatase activity
o Regulated by LH and FSH
Progesterone
o Corpus luteum – tiny amount from follicular theca cells
o Regulated by LH (via Camp)
Inhibin B (inhB) o Secreted CL granulosa cells granulosa cells – inhibit anterior pituitary FSH secretion
Effects of estrogens
- Facilitate growth of ovarian follicles + uterine tube motility
- Cyclical changes in endometrium
- Increased blood flow + smooth muscle contractility of uterus
- Oestrogen dominated uterus is more sensitive to oxytocin
- Increases breast duct growth
Feedback of oestrogen’s
- Inhibits FSH
* LH – complex, either increase or decrease
Progesterone effects
Uterus – progestational changes in endometrium, cervix and vagina
Antioestrogenic effects – prevents uterine contraction
o Reduces excitability, oxytocin response, number of ERs
Breast – stimulates lobule + alveoli devt, supports lactation
Brain – stimulates thermogenesis and respiration
Feedback of progesterone
Inhibits LH - prevent ovulation
Follicular changes in the follicular phase of the ovarian cycle
- Several follicles enlarge, cavity forms around ovum (antrum) filled with follicular fluid
- 10-15 days before ovulation – dominant follicle starts to grow rapidly, others regress (apoptosis – atretic follicles)
- estrogen is now produced from ovary granulosa cells (via theca interna cells)
- oocyte increases zone pelucida (glycoprotein shell)
When are ALL oocytes formed by?
7 months gestation
What inhibits other primordial cells from entering the primary follicle transition>
Granulose cell aMH or pre-astral follicles
The luteal phase
- After ovulation (d14), ruptured follicle fills with blood corpus haemoragicum
- Granulosa/theca cells proliferate corpus luteum (lipid-filled)
a. CL secretes megadoses of progesterone + oestrogen
b. plus lots of VEGFa + Fgf2 vasculogenic
c. CL growth
2 things the LH surge causes
- Theca externa releases proteolytic enzymes (collagenase) dissolve follicular capsule wall degeneration of the preovulatory opening (stigma).
- Prostaglandins follicular tissue smooth muscle contraction of the follicle ovum expulsion
What causes the LH surge?
¥ GnRH LH+FS Prog, inhB (-ve fbk), + oest
¥ Oestrogen has 2 opposing effects on ant. pit. LH secretion:
Moderate, constant oestrogens suppress GnRH + LH secetion
Aberrantly elevated oestrogens increase GnRH + LH secretion
When does the fertilised oocyte become a blastocyst and implant?
Blastocyst: by day 4
Implantation: 6-9 days post conception
Endocrine changes post conception
¥ CL fails to regress enlarges secretes oest, prog, relaxin (inhibits myometrial contraction maintains pregnancy)
¥ Implanting syncytiotrophoblasts form placenta
o Mother’s endometrial tissue also contributes to placenta
¥ Placenta becomes a hormone-secreting factory!
Primary and secondary ageing
1°aging: intrinsic changes occurring with age, unrelated to disease or environmental influences
2°aging: changes caused by the interaction of primary aging with environmental influences or disease processes
Evolutionary mechanisms of ageing
Mutation accumulation - Any mutations that result in a post-reproductive reduction in fitness will not be removed by natural selection
¥ GBA, LRRK2, SNCA (PD), Huntingtin, et al.
Antagonistic pleiotropy – a gene that exerts a small pre-/reproductive benefit and a large post- reproductive cost will still be selected for
¥ P53 activating mutations (anti-tumour, ↓ lifespan)
Programmed theories of ageing
Programmed theories:
¥ Neuroendocrine: biological clock and endocrine control
¥ Immune: immune system is a pacemaker of ageing
¥ Finite cell division: cells stop dividing after finite number of divisions
Wear and tear theories of ageing
¥ Free radicals: FR damage accumulates ageing
¥ DNA damage: DNA damage accumulates ageing
¥ Aggregation: proteins become aggregated, not cleared
¥ Recycling failure: old/dysfunctional proteins not cleared
Cellular and molecular processes that cause ageing
- Damage caused by oxidative stress
- Inadequate repair of damage
- Dysregulation of cell number
How cells respond to damage/replicaiton
Ð Arresting growth of old/damaged/dysfunctional cells (anti-cancer)
Ð Beneficial early in life; may contribute to aging later - altered secretion of proteases, cytokines and growth factors
Senescence effect on skeletal cells
¥ Late 30s ↓1-2% mass/year, >75 yo accelerates
• ↓myofibre size + number
¥ Myogenic or neurogenic? ↓ activity + MNloss
Senescence effect on bone remodelling
– Starting in middle age, resorption>formation progressive mass loss
– Menopause accelerates loss
Senescence effects on synovial joints
– joint flexibility declines, articular cartilage thins, and↓tensile
stiffness, fatigue resistance, and strength.
– ↑glycosylation & collagen cross-linking, loss of proteoglycans.
– Loss of elasticity, tendency towards osteoarthritis
Senescence effects on CNS
- Atrophy 0.1% per year 20 to 60, then 0.5% after 70
- Diffuse uniform increase in cortex and hippocampus, ventricles expand
- Aggregate accumulation
- Reduced neurotransmission
Senescence effects on pNS
- Reduced regenerative response
- Demyelination/axonal atrophy/electrophysiology slowed conduction
- Damped signal transduction
- Reduced beta adrenergic and muscarinic responsiveness
- Reduced response to beta blockers
Sensory effects from senescence
- Touch, vibration, spatial distinction, proprioception, vestibular function
- Hearing loss (esp. high-frequency)
- Vision deteriorates
- Central processing deficit difficulty distinguishing spoken words from background noise
- Taste & olfaction modality qualities deteriorate
Effects of senescence on motor functions
- Slowing of central processing
* Reduction in simple response, greater reduction in complex ones
Pulmonary function in senescence
- reduced respiratory muscle strength and endurance – atrophy of type 2a myofibres
- lung volumes (static and forced) reduced gradually
a. reduced vital lung capacity, RV, FEV1 - Lung elasticity (compliance)
a. Collagen and elastin degenerate
b. Small airways collapse (atelectasis)
c. Results in impaired ventilation, increased V/Q mismatch and lowers resting PaO2
