BIOL1040 - Cell Membranes, Reproduction and Development

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Fluid mosaic model

Cell membrane is fluid with a mosaic of proteins embedded in it

Evidence for fluid mosaic

Dyed membranes of mouse and human proteins different colours

fused cells and examined proteins after an hour

result - proteins mixed, showing there is lateral movement

Movement of phospholipids in membrane

continuous lateral movement (10^7 times a second)

• means embedded proteins can move around

flip flop (~once a month)

What affects membrane fluidity?

Unsaturated hydrocarbon tails

• form kinks in tails, making them more rigid

• can’t pack as closely together

• more fluid membrane

Saturated tails

• pack closely together as tails flexible

• more viscous membrane

Cholesterol

• acts as temperature buffer

• high temp = more fluid, cholesterol acts to decrease fluidity

• low temp = more viscous, cholesterol acts to decrease viscosity

Integral membrane proteins functions

• transport

• enzymatic activity

• signal transduction

  • receptor for ligand to bind to

• cell-cell recognition

• cell-cell attachment/ intracellular joining

  • used to make tissues

• attach to cytoskeleton and ECM

Osmosis

Diffusion of water through selectively permeable membrane into another aqueous compartment containing a non-permeable solute at a higher concentration

Osmotica

Solutes that are osmotically active

• won’t pass through membrane, exert osmotic pressure which drives movement of water to balance out this solute concentration

Osmotic pressure

Force that causes water to move to negate a concentration gradient

Facilitated Diffusion

Passive transport sped up by integral membrane proteins

Types of integral membrane proteins used in facilitated diffusion

Carrier/Transporter

Channel

Channel protein and examples

Provides channel for hydrophilic particles such as ions to travel down concentration gradient

no work required (no ATP)

examples

• aquaporins - for water

• ion channels - open and close in response to stimulus (gated)

Carrier/transporter protein 

solute binds to protein in extracellular open configuration, changing conformation to intracellular open allowing solute to enter cell

e.g., glucose, amino acid transporters

Active transport

goes against concentration gradient, requires ATP

mediated by transporters, not channels since channels would just let the solute back down concentration gradient

Electrogenic pump

creates voltage across membranes by moving ions

• sodium/potassium ATPase

• proton pump

Cotransport

active transport of one solute indirectly drives another

e.g., proton gradient from proton pump drives sucrose H+ cotransporter in plants, sodium potassium ATPase cotransports glucose in animals

Endocytosis types

pinocytosis - cell drinking

phagocytosis - cell engulfing large particles or other cells

receptor mediated endocytosis - solute binds receptor, cell endocytoses bound receptors

Paracrine signalling

local - chemical molecules sent btwn cells

Autocrine signalling

local - cell secretes chemical that signals itself

Synaptic signalling

local - nerve cell releases neurotransmitters that innervate another nerve or muscle/other cell

Endocrine signalling

long distance - hormones travel through body fluid to trigger responses in specific target cells

Neuroendocrine signalling

long distance - neurosecretory cell secretes neurohormones which travel through body fluid to trigger responses in target cells

Stages of cell signallng

Reception

• ligand bind to receptor

  • cell surface if hydrophilic

  • inside cell if hydrophobic

Transduction

• convert to different energy or messenger within cell

• amplification of signal

Response

Receptor families (list, 2 families, 3 receptors in the first, 1 in the second)

Plasma membrane receptors

• G-protein coupled receptors

• Ion channel receptors

• Receptor tyrosine kinases

Intracellular receptors

• Steroid receptors

Ion channel receptors

ligand gated ion channel

ion channel opened by ligand

fast - good for neurotransmission

GPCR

Largest family of receptors

7 transmembrane spanning regions

Activated by variety of stimuli

GPCR coupled to heterotrimeric (3 parts) G protein

Signal amplification

Process

• first messenger binds to GPCR, activates

• GPCR binds to G protein, bound by GTP which activates it

• G protein binds to adenylyl cyclase, GTP hydrolysed, activating adenylyl cyclase

• activates second messenger (e.g., cAMP) leading to cellular response 

Receptor Tyrosine Kinases

Reception - RTKs dimerise on membrane, binding (active)

Transduction - phosphorylation cascade amplifies signal, mediated by kinases (enzymes that phosphorylate)

Response - several at once

Used for metabolism, cell growth, cell reproductio

Role of protein phosphorylation

• conformational change

• different binding

• protein may move to different location

Steroid Receptors

receive hormones intracellularly

slower response

can act as transcription factors by binding DNA to nucleus

Difference btwn male and female gametes

female = large and non motile

male = smaller, motile

Internal fertilisation advantages and disadvantages

moist environment created

sperm deposited in or near female reproductive tract

little to no loss to environment

protection from predation or dispersal

External fertilisation advantages and disadvantages

can have lots of reproduction happening

BUT

loss to environment

dispersal

vulnerable to predation

moist habitat required

timing important

Placental mammals development

15% internal

use placenta to nourish developing embryo

mammal mothers provide milk and care

consequence - fewer offspring

Marsupials development

0.12% internal

small placenta disappears quickly

source of nourishment from egg yolk

embryo born in premature stage compared to placenta mammals

complete external development in pouch containing mammary glands

oestrous cycle exceed gestation period

• some animals in oestrous can mate while having egg already fertilised

• 2 uteri = multiple offspring in develpment

• development of 2nd embryo arrested at blastocyst - embryonic diapause

Monotreme development

0.08% internal dev

egg incubates short time

hatches, feeds off lactating mother

• milk from hair not nipples

tiny uterus

Sexual reproduction advantages/disadvantages

pros

• genetic diversity

• facilitates adaption

• speeds up evolution

cons

• energy intensive

• courtship time and resource consuming

• usually sacrifice fitness of one sex

Asexual reproduction advantages/disadvantages

pros

• save energy

• no courtship

• greatest fitness for all individuals

• works best in stable environment

cons

• low genetic variability

• adaptation to new environments difficult

• slows down evolution

Types of asexual reproduction

binary fission

multiple fission

budding

fragmentation

parthenogenesis

Types of parthenogenesis

haploid parthenogenesis

• results in fertile haploid offspring

• e.g., honey bees

• reduces genetic diversity 

diploid parthenogenesis

• automixis

  • meiosis, fusion of two oocytes

  • some genetic diversity from recombination

• apomixis

  • mitosis to produce diploid egg which becomes diploid individual

  • genetically identical individuals

Pineal gland

responds to light

controls seasonal breeding - breed when conditions favourable

melatonin

Pheromones

usually olfactory chemicals secreted by one organism influence another’s behaviour and physiology

Leydig cells

produce testosterone in response to LH from pituitary

Spermatogenesis steps

• primordial germ cell

  • mitosis

• spermatogonial stem cell (2n)

  • mitosis

• spermatogonium (2n)

  • mitosis

• Primary spermatocyte (2n)

  • meiosis I

• Secondary spermatocyte (n)

  • meiosis II

• spermatids

  • differentiation (Sertoli cells)

• spermatozoa/sperm cells

  • move to epididymis for storage/maturation

from outside inwards in seminiferous tubules

Male reproductive organ and major components + functions

Testes

• Leydig cells

  • produce testosterone in response to LH from pituitary

• seminiferous tubules

  • site of spermatogenesis

    • from outside to inside

  • sperm cells travel through lumen to reach epididymus

  • Sertoli cells

    • stimulated by FSH to nourish spermatids as they differentiate into spermatozoa

• epididymis

  • site of sperm storage and maturation in each testicle

• vas deferens

  • muscular duct

  • during ejaculation, sperm propelled from each epididymis down vas deferens to urethra

• urethra

  • transport urine and sperm out of body

• corpus cavernosa

  • tissues fill with blood during erection, allowing penis to become erect

• corpus spongiosum

  • surrounds urethra, keeping it open during ejaculation, urination

  • forms glans penis (sensitive tip)

• accessory glands (prostate glands, bulbourethral glands, seminal vesicles)

  • produce secretions that combine with sperm to form semen

• scrotum

  • maintains testes 2 degrees below core temp

T

testicles

TE

Epididymis

DD

Vas deferens/ ductus deferens

UB

urinary bladder

VG

vesicular gland (seminal vesicles)

BP

prostate gland

BUG

bulbourethral gland

Sperm structure

Acrosome

• on top of head, contains enzymes

nucleus

• in head region

mitochondria

• in midpiece

flagellum

• tail for movement

Oogenesis stages

• primordial germ cell

  • mitosis

• oogonium (2n)

  • mitosis

• primary oocyte (2n)

  • arrested at prophase I until puberty, where FSH stimulates development

  • unequal cytokinesis forming 1st polar body

• secondary oocyte (n)

  • arrested at metaphase II until fertilisation

  • ovulation, rupturing of follicle

  • completion of metaphase II after fertilisation, release of second polar body

• Ferilised egg

Ovaries

female gonads

primary site for release of oestrogen

site of oogenesis

ruptured follicles after ovulation become corpus luteum

• secretion of oestradiol and progesterone

ovulation

• ovary releases mature egg down fallopian tube to uterus

Follicles and development

cavity lined with protective cells

follicle grows with oocyte until mature with secondary oocyte

• primary follicle = one layer of cells

• secondary follicle = multiple layers of cells + zona pellucida, primary oocyte

• tertiary/Graafian follicle = fluid filled cavity called antrum 

during ovulation Graafian follicle ruptures

corpus luteum forms

• oestradiol + progesterone

corpus luteum degrades

Oviduct/fallopian tubes

extends from each ovary to uterus

site of fertilisation

cilia and wavelike contractions of oviduct move egg

transport fertilised eggs to uterus for implantation

environment for fertilised egg to undergo cleavage and become blastocyst

Uterus

Endometrium

• inner lining

• thickens and increases in vascularity during ovulation to support implantation

• shed if no implantation, menstrual cycle repeats

• endometrial gland

  • tubular structures within endometrium

  • secrete nutrient-rich fluids to nourish developing foetus

  • source of endometrial regeneration after shedding

myometrum

• thick middle layer

• smooth muscle

• contracts during labor to push out baby

• does not shed

placenta

• allows for exchange of nutrients, respiratory gases and waste btwn foetus and mother

umbilical cord

• connects foetus and mother’s placenta, facilitates transport btwn foetus and mother

Cervix

Connects uterus and vagina

produces mucus to block unwanted sperm and microorganisms

• during ovulation allows sperm to pass through and fertilse egg in oviduct

• remains closed during pregnancy to protect developing foetus

• widens during childbirth to allow baby to pass thorugh birth canal

Vagina

passage for sexual intercourse

passage during childbirth

O

Ovary

OD

Oviduct

UH

Uterine Horn

CX

Cervix

CV

Cranial vagina (upper portion, closer to cervix

Ve

Vestible/caudal vagina - lower portion of vagina

UB

bladder

Gonadotropin releasing hormone

GnRH

Released by hypothalamus

Acts on anterior pituitary

Gonadotropins

Follicle stimulating hormone (FSH)

Luteinising hormone (LH)

travel through blood to reach gonads

• androgens released in males (testosterone)

• oestrogens released in females (oestradiol, progesterone)

FSH

secreted by anterior pituitary

males

• stimulates sertoli cells to nourish sperm

females

• stimulates growth and maturation of follicle

Luteinising hormone

secreted by anterior pituitary

males

• LH causes Leydig cells to produce testosterone and other androgens to promote spermatogenesis

females

• stimulates ovaries to produce oestrogen

• triggers ovulation

• maintains corpus luteum

Hypothalamus regulation of gonadotropins

Hypothalamus responsible for secretion of GnRH

GnRH stimulates LH and FSH production by the anterior pituitary

LH and FSH stimulate gonads to release androgens/oestrogens

Androgens/oestrogens have negative feedback effect on hypothalamus, controlling levels of GnRH if levels of androgen/oestrogen get too high

Negative feedback very sensitive before puberty

Inhibin

Produced by sertoli cells in testes

acts on anterior pituitary to reduce FSH

Androgens in males cause

penis and scrotum to grow

facial hair

larynx elongates

shoulders broaden

public hair grows

musculature increases

Oestrogens in females cause

breasts develop

hips widen

pubic hair grows

What controls sex phenotype?

genotype + hormones

Jost removed portion of embryo that would become gonads

• become female even if had male chromosomes

chromosomes not enough to determine sex, need further signals from gonads

Gene on Y chromosome (SRY) determines whether testes produce testosterone

Ovarian cycle

Follicular phase

• FSH stimulates follicle maturation

• follicles produce oestradiol → endometruium thickens

Ovulation

• triggered by LH surge

• secondary oocyte released into oviduct

Luteal phase

• corpus luteum releases oestradiol, progesterone

  • inhibits hypothalamus

• corpus luteum degrades if no pregnancy

• uterine lining shed

Follicular phase

• FSH secreted

  • low levels of oestradiol inhibit FSH and LH for most of this phase

• follicle matures in ovary

• follicles produce oestradiol

  • signal endometrium to thicken

• one dominant follicle grows and prepares to release egg

• this phase coincides with proliferative phase of uterine/menstrual cycle

Ovulation

• peak in oestradiol causes LH surge which triggers ovulation

• mature follicle ruptures

• secondary oocyte released into oviduct

• middle of cycle

Luteal phase

• LH stimulates ruptured follicle to form corpus luteum

  • secretes progesterone and oestradiol, -ve feedback on hypothalamus

    • reduces LH and FSH, preventing another egg from maturing

  • low LH and FSH cause corpus luteum to degrade if no pregnancy

    • sharp decline in oestradiol and progesterone

      • uterine lining shed, cycle restarts

Uterine cycle

Cyclic change in endometrium that occurs in absence of pregnancy

menstrual cycle in humans

synched with ovarian cycle, hormone activity synchronises ovulation w establishment of uterine lining which can support embryo implantation and development

Menstrual cycle

Proliferative phase

• oestradiol secreted by growing follicle signals endometrium to thicken

• corresponds w follicular phase

Secretory phase

• after ovulation, oestradiol and progesterone secreted by corpus luteum maintian uterine lining and further devleop endometrial glands

  • secrete nutrient fluid to nourish b4 implantaton

• corresponds w luteal phase

Menstrual flow phase

• if no implantation, corpus luteum degrades, sharp drop in oestrogens

• endometrium shed

• menstruation

  • release of blood, endometrial tissue, fluid

Oestrus cycle

Endometrium reabsorbed in absence of pregnancy

During oestrus is only time females r receptive to mating

4 phases

• anestrus

  • not receptive to mating

• proestrus

  • follicles develop, oestrogen rises

• estrus

  • heat, period of sexual activity

• diestrus

  • corpus luteum

Oestrus

State where female mammals are sexually receptive and willing to mate

monooestrus = oestrus once a year

polyoestrus = oestrus multiple times a year

can be induced by mating (presence of semen)

Seasonal polyestrus

regulated by pineal gland

• seasonal variation in light triggers diff levels of melatonin

• linked to breeding hormones and behaviour

can be long and short day mating

• receptive to mating only when length of day right

Fertilisation process

+ve sperm attracted to -ve egg membrane

sperm meets egg

acrosome reacts with zona pellucida, releasing enzymes to dissolve it

acrosome reacts with perivitelline space, binds to sperm binding receptors

• causes Ca2+ release and membrane depolarisation

plasma membrane of sperm and egg fuse

sperm nucleus enters egg

fast or slow block to polyspermy occurs

Fast block to polyspermy

not in mammals

Na influx after sperm-egg fusion (1-3 s after sperm enters egg)

• +ve charge discourages other sperm

• shift in membrane potential from -70mV to +20mV through ion channel

Slow block to polyspermy

in mammals

Cortical reaction

• cortical granules released triggered by calcium release when sperm binds to receptors

• release of cortical granules which contain enzymes and macromolecules

• lift up vitelline layer which forms fertilisation envelope

  • hardens to prevent sperm entry, chops off sperm binding receptors

Embryo development stages

Fertilisation

Cortical rotation

Cleavage

Blastulation

Gastrulation

Organogenesis

Cortical rotation

Plasma membrane and cortex (region just below membrane) rotate relative to inner cytoplasm

point of sperm entry becomes animal pole (smaller cells

Cleavage

Rapid cell division via mitosis

only M and S phase

stage ends when not enough cytoplasm to divide - too little RNA to meet protein needs of cell

results in morula (ball of cells)

Types of cleavage

Complete - holoblastic division

• if less yolk (e.g, sea urchin)

  • equal cleavages

  • blastomeres of similar size

• if yolk only in specific region (e.g., frogs)

  • cleavages unequal

  • cells in yolky region (vegetal pole) chunkier

Incomplete - meroblastic division

• if a lot of yolk (e.g., chickens)

  • cleavage furrow slowed or blocked by yolk

  • complete divisions restricted to less yolky areas

  • Flat disk of incompletely cleaved cells on top of yolk

Blastulation

morula rearrangement into blastula

• inner layer = embryoblast

• outer layer = trophoblast

  • provides nutrient to embryo

  • form placenta

• hollow cavity = blastocoel

implantation

• trophoblast secretes enzymes that digest endometrium, allowing implantation

post implantation

• trophoblast expands forming placenta

• 4 extraembryonic membranes

  • amnion

    • encloses developing embryo

    • contains amniotic fluid to provide moist environment 

  • 3 other membranes

Gastrulation

reorganisation of blastula into 3 distinct layers

• ectoderm

  • outer layer, covers embryo

  • forms outer layer of skin

  • forms nervous system from neural plate

• mesoderm

  • middle layer

  • forms muscle, skeleton and connective tissue

• endoderm

  • innermost layer

  • lines digestive tract

  • forms internal ducts and organs such as liver, pancreas and lungs

formation of archenteron

• primary digestive tube formed by invagination

organogenesis

Cells differentiate into organs

• neurulation, formation of nervous system is first

• heart is one of first organs to form

• muscles from somites

• limbs form from limb buds

Organ differentiation - fate mapping

• where cells need to be and what they end up being is preprogrammed

  • dictated by gene expression and protein signaling

• determination

  • establishes a cell/group of cell’s fate

• differentiation

  • process of specialisation in structure and function

• bilateral symmetry

  • left/right axis symmetrical

  • head/tail axis asymmetric

    • melanin fills animal hemisphere

    • yolk fills vegetal hemisphere (more nutrients)

    • hemispheres determined by cortical rotation

Neurulation

• formation of nervous system

• process

  • some mesoderm cells form notochord

    • rod that extends along dorsal side of embryo

    • eventually forms spinal cord

  • signal from notochord causes inward folding of ectoderm at neural plate (area above notochord)

  • ends of neural plate fuse and disconnect to form autonomous neural tube

limb formation

cells in limb buds release inductive signals (proteins) to themselves and each other

combined with gene expression this determines

• spatial orientation

• arrangement of organs and tissues

the limb bud determines the formation of a limb, if limb bud was transplanted somewhere else that limb would still grow

Frog embryo developmental comparison

gastrulation - cells move quickly

less developed when hatched as tadpole bc tadpole further develops into frog

Chick embryo developmental comparison

cleavage

• incomplete due to yolk (meroblastic division)

gastrulation

• blastula is flat disk

• cells migrate to middle of disk to form primitive streak

• cells at primitive streak migrate downwards to form 3 layers

• neural groove forms where primitive streak is, gets deeper to form neural tube (spinal cord)

clearly defined organs and limbs at end of development

Hormones during embryo development (trimesters and labour)

1st trimester

• human chorionic gonadotropin (hCG) secreted

  • acts like LH from the pituitary

  • maintains corpus luteum (progesterone and oestradiol secretion)

2nd trimester

• hormone level stablise

  • hCG secretion declines

  • corpus luteum deteriorates

• placenta completely takes over production of progesterone

Labour

• 2 hormones

  • oestradiol

    • from ovaries

    • activates oxytocin receptors on uterus

    • helps oxytocin bind to uterus wall to cause contractions

  • oxytocin

    • from foetus’ and mother’s posterior pituitary

    • stimulates contraction of uterus

    • stimulates placenta to make prostaglandins to stimulate more contractions

    • positive feedback loop

Placenta (purpose, blood flow, material exchange mechanisms)

inside endometrium

purpose

• exchange gases, nutrients, waste btwn foetus and mother

maternal blood

• through arteries into maternal blood pools in endometrium, out through veins

foetal blood

• stays in vessels

• through arteries to capillary beds in maternal blood pools, out through veins

material exchange

• diffusion

• activate transport

• selective absorption (things like glucose) btwn foetal capillary bed and maternal blood pools

When do we use contraception?

any time before implantation