DEVELOPMENT AND INHERITANCE TERMINOLOGY OF DEVELOPMENT For first 8 weeks after fertilization embryo After that foetus Prenatal

natal period (before birth) o o divided into trimesters, each 3 months long 1st is most critical (mostly) major organ systems established foetus highly vulnerable to toxins, radiation, infections o o during 2nd organ development nearly complete during 3rd have rapid growth, completion of organs FERTILIZATION 200 million sperm enter vagina at ejaculation < 2 million reach cervix Ocyte viable in uterine tube for about 24 hours, sperm for about 48 hours o 3 day window of opportunity around ovulation ~ 200 reach ocyte

Sperm swims through vagina into cervical canal Once here, muscle contractions of uterus and uterine tube keep sperm moving along Sperm may reach ocyte in minutes, but cant yet fertilize egg

Sperm take about 7 hours to undergo capacitation o o flagellum beats more rapidly removal of cholesterol, proteins & glycoproteins from plasma membrane prepare it for fusion with that of the ocyte

Sperm has to get through corona radiata and zona pellucida, which is made of glycoproteins o o o one called ZP3 its a sperm receptor molecule binds to proteins in sperms head, releasing acrosomal contents digestive enzymes force of flagellum pushes sperm into ocyte

Multiple sperm may bind to ocyte, but only one will get through to ocytes plasma membrane Fusion of sperm and ocyte causes depolarization of the ocytes cell membrane o fast block against more sperm fusing Fusion also causes release of Ca2+ from ocytes smooth ER o causes exocytosis of vesicles beneath ocyte membrane

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enzymes released from vesicles deactivate ZP3 & harden zona pellucida slow block

All to prevent polyspermy fertilization by multiple sperm o zygote wouldnt develop if multiple sperm allowed to fertilize (why not?) Rise in Ca2+ also triggers completion of meiosis II Also activates rapid synthesis of new proteins EVENTS WITHIN THE EGG

Sperm entry triggers ocyte to complete meiosis II Sperm loses its tail & becomes a male pronucleus Fusion of male & female haploid pronuclei is the true moment of fertilization Fertilized ovum (2n) is called a zygote o zona pellucida still surrounds it ZYGOTE CLEAVAGE & FORMATION OF THE MORULA

Rapid mitotic cell division called cleavage 1st cleavage in 30 hours o produces 2 blastomeres 2nd cleavage on 2nd day By 3rd day has 16 cells By 4th has formed solid ball of cells called a morula DEVELOPMENT OF THE BLASTOCYST

Morula enters uterine cavity on day 4-5 Endometrial glands secrete fluid containing glycogen o uterine milk enters morula, provides nourishment

At 32 cell stage, cells of morula reorganize to form hollow sphere known as the blastocyst o fluid-filled inner cavity known as blastocoel

Cell number continues to increase to hundreds Rearrange to form inner cell mass, and outer cell layer o o outer layer called trophoblast most of inner cell mass will become embryo IMPLANTATION

After ~ 5 days, blastocyst escapes from zona pellucida o must do so in order to implant

Blastocyst remains free in uterine cavity for ~ 2 days, then loosely binds to endometrium in fundus or body of uterus o o o implants with inner cell mass toward endometrium attachment becomes firmer endometrium responds by enlarging local glands, and increasing vascularization

Trophoblast cells in contact with endometrium rapidly multiply o here, trophoblast wall becomes several layers thick

Cells in outermost layer merge, forming large cell with multiple nuclei a syncytium o referred to as syncytiotrophoblast

Inner layers form cytotrophoblast

Syncytial trophoblast secretes enzymes that allow blastocyst to push through epithelial cells lining uterus o o burrows into endometrium epithelial cells cover gap

Trophoblast secretes human chorionic gonadotropin o o similar effects to LH prevents degeneration of corpus luteum corpus luteum continues to secrete estrogens & progesterone prevents degeneration and sloughing of uterine lining o by 9 week placenta takes over progesterone/estrogen production ENDOMETRIAL CHANGES
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Endometrium now called decidua; has 3 parts: 1. Decidua basalis is endometrial layer between embryo and stratum basalis provides glycogen & lipids ultimately becomes maternal portion of placenta 2. Decidua capsularis is thin layer between embryo and uterine cavity 3. Decidua parietalis is remaining endometrium lining uterine cavity THE BILAMINAR EMBRYONIC DISC

Inner cell mass cells separate from trophoblast Gap formed is the amniotic cavity Inner cell mass cells differentiate about 8 days after fertilization 3

form 2 layers the hypoblast & epiblast ultimately become body of embryo

Epiblast is layer of columnar cells o will form ecto-, meso-, and endoderm

Hypoblast is layer of cuboidal cells o will form yolk sac THE AMNION

With formation of amniotic cavity, epiblast cells migrate to form amnion a thin membrane The amnion is the roof of the amniotic cavity o floor is epiblast

Amnion will eventually surround the embryo Fills with amniotic fluid o starts as filtrate from maternal blood, but foetus later adds to it with urine

Acts as shock absorber, insulation, prevents dehydration, prevents sticking to surrounding tissues Foetal cells slough off into fluid o used for amniocentesis THE YOLK SAC

Still on day 8, cells from hypoblast migrate over inner surface of blastocyst wall Flatten and form thin exocoelomic membrane o it and hypoblast form wall of yolk sac

Notice that the developing embryo is now sandwiched between the amniotic cavity and the yolk sac.

Yolk sac not for nutrients (except very early on) Contains primordial germ cells that will migrate to developing gonads to become spermatogonia or ogonia Also site of blood cell formation for 3rd to 6th weeks of life o then liver takes over DEVELOPMENT OF THE SINUSOIDS

Once blastocyst nicely embedded in endometrium (~ 9th day), entrance hole seals over with coagulation plug

Syncytiotrophoblast expands to surround yolk sac

small spaces open up within it - lacunae

Lacunae begin to fuse, creating a network Capillaries in endometrium surrounding embryo dilate, forming sinusoids Some broken down, along with endometrial glands, by syncytiotrophoblast o o blood & glandular secretions flow into lacunar networks nutrition and waste disposal for embryo DEVELOPMENT OF THE CHORION

Extraembryonic mesoderm cells develop, and migrate to surround yolk sac and amnion Cavities develop in this layer of cells Cavities fuse to form single cavity called extraembryonic coelom Extraembryonic mesoderm + original 2 layers of trophoblast = chorion o o o surrounds embryo/foetus becomes main embryonic part of placenta placenta is used for exchange of substances with mom

Chorion protects foetus from maternal immune system Secretes human chorionic gonadotropin hCG o keeps hormones from corpus luteum coming

Innermost layer fuses to amnion Primary chorionic villi form o trophocytoblast cells extend finger-like projections into syncytiotrophoblast k.a. primary chorionic villi o followed shortly by mesenchyme cells, creating core of loose connective tissue now secondary chorionic villi

At same time, extraembryonic mesoderm in region of bilaminar disc extends narrow stalk to connect to trophoblast o will become umbilical cord GASTRULATION

Bilaminar disc will become a trilaminar disc o o o involves formation of 3 primary germ layers endoderm, mesoderm, ectoderm everything in the body develops from these

Develop an oval, three-layered sheet = embryonic disc

Cells of epiblast begin migrating, forming primitive streak on dorsal surface o o runs anterior to posterior, establishing head/tail ends, right/left sides head end of streak is rounded primitive node

Epiblast cells at edges of primitive streak sink inwards o o invagination some push between hypoblast cells, displacing them creates endoderm o others stay between epiblast and new endoderm mesoderm o epiblast now forms ectoderm

Endoderm & ectoderm cells tightly packed Mesoderm much looser mesenchyme Endoderm will become G.I./respiratory epithelium Mesoderm will become muscle, bone, connective tissue, peritoneum Ectoderm will become skin epidermis, and nervous system

~ day 16, mesoderm cells in primitive node migrate towards head o form hollow tube = notochordal process

~ days 22-24, tube forms solid cylinder = notochord Secretes substance that induces nearby unspecialized mesoderm cells to start to become vertebral bodies o notochord ends up as nucleus pulposus of intervertebral discs

Small depressions at head and tail ends form o o o oropharyngeal membrane & cloacal membrane 4th week oropharyngeal membrane becomes oral cavity 7th week cloacal membrane becomes openings for anus and urinary/repro. tracts

Over same period, yolk sac produces extension into connecting stalk o o allantois minor role in human development

Notochord also gets ectoderm above it to form neural plate Edges of plate elevate & form neural fold Sunken midsection called neural groove Folds move toward each other & fuse, forming neural tube o begins at mid-embryo and moves to ends

Whole process is neurulation Ultimately, tube forms brain & spinal cord

About day 17, mesoderm near notochord/neural tube forms longitudinal column on each side o o o paraxial mesoderm lateral to this is intermediate mesoderm lateral to this is lateral plate mesoderm

Paraxial mesoderm will break up into chain of cube-shaped blocks of tissue o somites

Somites differentiate into myotomes, dermatomes & sclerotomes o o o myotomes skeletal muscle of neck, trunk, limbs dermatomes dermis & connective tissue sclerotomes vertebrae DEVELOPMENT OF THE PLACENTA

Embryonic portion is chorion Blood vessels develop in secondary chorionic villi o now (tertiary) chorionic villi

Blood vessels extend into embryo to heart via umbilical arteries & veins Puts embryonic circulation close to maternal o o no mixing of maternal/fetal blood oxygen, nutrients & wastes diffuse through tissues between

Maternal portion formed by stratum basalis Placenta pancake-shaped Allows nutrient/waste exchange Acts as barrier to microorganisms (except some viruses HIV, German measles, polio) Drugs, alcohol pass easily through 7

Umbilical cord is connection between mom and baby 2 umbilical arteries carry deoxygenated fetal blood to placenta 1 umbilical vein brings in oxygenated blood EMBRYOGENESIS & ORGANOGENESIS

Embryogenesis begins soon after gastrulation begins Involves taking 2D embryonic disc & folding into 3D cylinder Ends form bulges known as head fold & tail fold Embryo now has distinct ventral/dorsal, anterior/posterior, left/right During remainder of 1st trimester, major organs begin to form organogenesis

Notice that there is also folding of the lateral margins of the trilaminar disc o o o fold ventrally gradually wrap around part of yolk sac becomes primitive gut tissue will differentiate, forming foregut, midgut, and hindgut

Pharyngeal arches (5 pairs) develop during 4th week o o o o found either side of head & neck endoderm/mesoderm/ectoderm within each are an artery, a cranial nerve, cartilage & muscle tissue become various head/neck structures e.g. thyroid gland

On side of head, otic placode appears future ear Anterior head lens placode first evidence of eye

Upper and lower limb buds form o mesoderm covered by ectoderm

Heart prominence shows where heart is Embryo still has a tail at end of 4th week CHECKING UP ON THE FOETUS

Fetal Ultrasonography Transducer emits high-frequency sound waves o o reflected sound waves converted to on-screen image called sonogram patient needs full bladder (acts as landmark)

Used to determine fetal age, viability, growth, position, twins and maternal abnormalities AMNIOCENTESIS

Fetal cells from 10 ml sample of amniotic fluid examined for genetic defects Test at 14-16 weeks Results back in one month Needle through abdominal wall & uterus Chance of spontaneous abortion is 0.5% CHORIONIC VILLI SAMPLING

As early as 8 weeks Results in few days Chance of spontaneous abortion 1-2% 30 mg of placenta removed by suction through cervix or with needle through abdomen Chromosomal analysis reveals same results as amniocentesis HORMONES OF PREGNANCY

Chorion o o from day 8 until 4 months secretes hCG which keeps corpus luteum active corpus luteum produces progesterone & estrogen to maintain lining of uterus & prepare mammary glands

Placenta o by 4th month produces enough progesterone & estrogen that corpus luteum no longer important o o relaxin increases flexibility of pubic symphysis & helps dilate cervix human chorionic somatomammotropin (hCS) (a.k.a. human placental lactogen, hPL) maximum amount by 32 weeks help prepare mammary glands for lactation o corticotropin-releasing hormone (CRH) increases secretion of fetal cortisol (lung maturation) & acts to establish timing of birth MATERNAL CHANGES DURING PREGNANCY

Uterus nearly fills the abdominal cavity GI tract compressed causing heartburn & constipation Pressure on bladder causing changes in frequency & urgency Compression of vena cava causing varicose veins & edema in the legs Compression of renal vessels causing renal hypertension 9

Cardiovascular changes to meet needs of fetus o o o rise in cardiac output of 20-30% due to placenta due to increase in both heart rate & stroke volume total maternal blood volume up by 30 50%

Respiratory changes o o o increase in tidal volume 30 40% decrease in expiratory reserve volume & airway resistance minute ventilation increases as O2 needs increase

Reproductive system changes o o uterus increases in size from ~ 80 g to ~ 1200g due to hyperplasia and hypertrophy in myometrium

Urinary system changes o o increase in glomerular filtration rate of 40% goes up to handle extra wastes from foetus LABOUR

Refers to expulsion of foetus from uterus o parturition means giving birth

Placenta has been secreting progesterone in order to maintain pregnancy o has to be overcome

Placenta begins secreting corticotropin-releasing hormone Gets fetal anterior pituitary to secrete adrenocorticotropic hormone

Foetal ACTH gets foetal adrenal gland to secrete cortisol & dehydroepiandrosterone (DHEA) Placenta converts DHEA to estrogen Increased estrogen level gets uterine muscle cells to put up oxytocin receptors & to link up via gap junctions

Posterior pituitary secretes oxytocin, stimulating contractions Relaxin also from the placenta increases pubic symphysis flexibility & dilates cervix

Prostaglandins from placenta cause production of proteases that digest collagen in cervix, softening it

Contractions push baby into cervical canal, stretching canal

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Positive feedback loop established & runs until baby born Contractions begin at top of uterus & move down True labour contractions regular, painful, increasing in frequency & intensity, back pain (made worse by walking)

False labour contractions irregular, no increase in pain

3 stages of labour: 1. Dilation beginning to full dilation of cervix about 6 12 hours, regular contractions, bursting of amniotic sac 2. Expulsion takes 10 minutes to several hours to complete passage of baby through cervix 3. Plancental 5 30 min., expulsion of placenta, contraction of damaged blood vessels 1st baby generally takes longer than subsequent avg. 14 hours o later about 8 hours

Foetus may be squeezed for hours within cervical canal Periodic hypoxia causes foetal adrenal gland to secrete large amounts of (nor)epinephrine o serve to clear lungs, prepare for breathing, enhance blood flow

If 2 weeks late, risk of foetal brain damage/death o hypoxia, malnutrition due to deteriorating placenta

Induce birth through oxytocin or do caesarean section BABY MAKES ADJUSTMENTS TO NEW REALITY

In uterus, foetal lungs full of amniotic fluid or collapsed At end of 6th month, surfactant production begins By 7th month, respiratory system fairly complete o can survive birth

At birth, umbilical connection cut no O2 in, nor CO2 out CO2 builds, stimulating respiratory centre BREATHE! Usually extremely deep as lungs contain no air Exhalation very forceful cries 1st 2 weeks, resp. rate ~ 45/min

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Breathing leads to cardiovascular changes Foramen ovale closes & deoxygenated blood begins flowing to lungs Ductus arteriosus closes, deteriorates Umbilical arteries fill with connective tissue o umbilical vein round ligament of liver

Ductus venosus took blood straight to heart, bypassing liver o now collapses, and blood flows to liver via hepatic portal vein, then to heart via inferior vena cava

Pulse rate at birth ~ 120 160 beats/min Production of RBCs & haemoglobin goes up to meet new oxygen demands White blood cell count begins to drop from high of up to 45,000 per microlitre WHY BABY LOOKS LIKE YOU GENETICS

Product of combination of maternal + paternal genes Traits inherited Set of genes baby has is genotype Expression of those genes is phenotype Genes determine characters Versions of genes, known as alleles, determine character traits A mutation is a permanent change from one allele to another

Some alleles show dominant/recessive relationship 2 copies of every allele If both different, one always expressed, the other not Dominant allele usually symbolized by capital letter, recessive by lower case e.g. P vs. p

If know parental genotypes, can make predictions about babys genotype Text uses example of phenylketonuria Have gene, P, with alleles P and p o o P codes for functional enzyme, p codes for non-functional enzyme breaks down phenylalanine

As long as have some functional enzyme, O.K., so only requires 1 P 2nd allele can be p, but wont matter 12

If know parents genotypes, can predict chances of baby having phenylketonuria People who carry 2 copies of an allele, PP or pp, are homozygous Heterozygotes (Pp) are said to be carriers of the recessive trait Important if being homozygous for recessive trait leads to disease o phenylketonuria

Each gamete needs one copy of gene Moms genotype: Pp Dads: Pp Both are heterozygous Half of each of their gametes will carry P, and half p

Punnett square can be used to determine probability of their having an affected baby A Punnett square is a simple graphical means of assessing what to expect from certain matings o o o draw a box & divide it into four show one parents alleles across the top and the others down one side fill in the boxes

In case of 2 carrier parents, can see that 3 out of 4 combinations produce healthy offspring o 1 in 4 will have the disease (i.e. 25% chance) DOMINANT NORMAL!

Huntingtons disease o dominant allele causes degeneration of nervous system and sure death doesnt kick in until late 30s, 40s note that this is after most people have had kids, so can get passed on

If prospective parent has parent who had Huntingtons, can get tested for presence of allele No cure really want to get tested?

Not all genes show dominant/recessive pattern Some show incomplete dominance o both get expressed, show as blend of 2 traits HbA codes for normal haemoglobin HbS codes for sickle cell haemoglobin 13

Sickle cell disease works this way o o

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HbA HbA = normal hemoglobin HbS HbS = sickle cell HbS HbA = both

Some genes have >2 alleles in the human population (though 1 person can only have 2) Blood types A, B, AB, O Alleles IA, IB, i A = IA IA, B = IB IB, AB = IA IB, O = ii Because IA and IB can be simultaneously expressed and distinctly seen, said to be codominant

Some traits controlled by multiple genes, each with 2+ alleles = polygenic inheritance Or, multiple genes, 2+ alleles, plus environmental factors = complex inheritance o skin colour, eye colour, hair colour, height

Means single genotype can have multiple phenotypes, depending on environment o e.g. might have genotype calling for tall, but inadequate diet leads to short

Skin colour is another example Depends on genes, nutrition, sunlight If alleles A, B, C = dark skin & a, b, c = light, combinations will yield variety of shades

The sex chromosomes, X and Y, are different from other homologous chromosomes X carries much more information than the Y Since mom can only send Xs on in gametes, while dad can send either an X or a Y, its the sperm that determines babys sex

Up to 7 weeks, all foetuses develop same way At 7 weeks, if SRY region of Y chromosome present, foetus heads off down male developmental path

If not, develops as female

Some characters only have genes on the X chromosome, so males will only get 1 allele Known as sex-linked inheritance Cause of colour blindness Gene designated C, alleles C and c Genotypes CC and Cc have normal colour vision, cc colour blind 14

Only applies to females since have 2 Xs Males only have either C or c since only have 1 X

A more serious sex-linked trait is haemophilia Dangerous because of uncontrolled internal bleeds o build-up of fluid pressure in tissues causes necrosis

Having 2 Xs has its drawbacks May lead to genomic conflict within a cell Solution inactivate one of the Xs One will condense and become inactive Barr body Done through addition of chemical groups to DNA that prevent transcription to RNA Only uncoils during mitosis Selection of X to inactivate is random in each cell o can have interesting results Calico cats

Anything causing abnormal development of foetus (except genes) is called a teratogen o alcohol, various drugs, pesticides, thalidomide

Cause variety of problems mental, physical o o smoking associated with low birth weight, high foetal mortality radiation induces mutations in genes THATS IT, FOLKS

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