PATH 201 - LECTURE 16

what type of infections can cross the placenta

• most parasitic and viral infections

• few bacterial infections

when do transplacental infections occur during gestation

anytime

how do infections cause defects

• can interfere with early development or destroy strucutres that are already formed

how do these infections cross the placenta

• direct infection of the out layer of the chronic villi which is called the syncytium

• infection could reach the extravillous trophoblasts and then cross into the villi

• inflammatory factors can attack and damage the villi - allowing breach

describe the rubella virus

• RNA rivus

• mild in children and adults

• serious impact is teratogenic effect

describe tertogenic effect of rubella

congenital rubella syndrome

when is the infection possibility of offspring getting CRS if mother is infected highest

• 1-12 weeks

• decreases over time after that

what can congenital rubella syndrome cause

ocular defects

auditoru defects

cardiovascular defects

CNS defects

examples of ocular defects caused by CRS - name 3

• cataract

• glaucoma

• retinopathy

• microphthalmia

• iris hypoplasia

• cloudy cornea

examples of auditory defects caused by CRS

• sensorineural deafness

example of cardiovascular defects caused by CRS

• persistent ductus arteriosus

• pulmonary artery stenosis

• ventricular septal defect

• myocarditis

example of CNS defects caused by CRS

• microcephaly

• psychomotor

• retardation

• meningoencephalitis

what is the molecular mechanism behind CRS that causes eye and ear impairment

• downregulation of genes involved in sensory organ development

describe the effect of RV on adult host cells

• causes apoptosis

describe effect of RC on primary foetal fibrolast cells

• doesnt undergo apoptosis - infection persists

• causes down regulation of genes

• disrupts actin filament assmeby and slows down cell division

describe how RV is prevented

• immunisation

• prepregnancy screening

describe formation and function of neural tube

• formed from neural ectoderm by week 4

• becomes spinal cord, spine, brain and skull

what are some examples of neural tube defects

• anencephaly - underdeveloped brain and skull

• spina bifida - spinal cord fails to develop and close nromally

• connection between aminotic cavity and spinal canal

what are neural tube defects caused by

genetic mutatons

exposure to environmental factors

maternal infection

maternal diabetes

low folic acid

irradiation

when is foetus most susceptible to neural tube defects and by

• first month gestation because that is when the neural tube is forming and closing

types of spinal bifida

• spina bifida occulta

• meningocele

• myelomeningocele

what is spinal bifida occulta

• small region of spine missing

what is meningocele

small bit of spinal fluid leaking out and filling a small bulge or sac but the cord is intact and running down

what is myelomeningocele

• most severe form of spinal bifida

• wehn the spinal cord is portruding out into the sac

how can spinal bifida be treated

• prenatal or psot natal surgery

how does folic acid deficiency cause neural tube defects

• folic acid is essential for synthesis of nucleotides, DNA synthesis, repair and methylation

• nucleotides are essential for mitosis in proliferating cells (neuroectoderm cells forming the neural tube)

what is the effect of normal pregnancy on glucose transport

• normal pregnancy causes insulin resistance so that less glucose is taken up out of the blood so that it stays in the blood and reaches the baby

what is the effect of pre-existing diabetes in mothers

• type 2 diabetes means insulin resistance

• so the high glucose in teh blood causes by diabetes in the mother causes foetal hyperinsulinemia - where the fetus produces too much insulin and causes excess glucoses uptake and storage

what are the effects of pre-existing diabetes

• still birth

• heart defects

• kidney diefects

• diabetes

• obesity

• hypertension

• ADHD

• autism

what is gestational diabetes

mother doesnt have diabetes

develops durign gestation due to too much insulin resistance during pregnancy

• occurs in 2nd or 3rd trimester

describe the effect on the offspring of gestational diabetes

• no major developmental effects because organs already formed

• fetal macrosomia - overgrowth - can cause birhting complications

what is foetal alcohol spectrum disorder

• group of disorders caused by prenatal exposure to alcohol

what are disorders under FASD

• foetal alcohol syndrome

• alcohol related neurodevelopmental disorder

• alcohol related birth defects

describe effect of prenatal alcohol exposure in 1st trimster

when in first trimester - more anatomical defects

what does later exposure to prenatal alcohol syndrome do

• subtle neurological defects as brain development continues

which FASD is msot severe

foetal alcohol syndrome

what are discriminating craniofacial anomalies of FASD

• microcephaly

• short palpebral fissures

• smooth philtrum

• thin upper lip

what are other associated craniofacial features of FASD

• epicanthal folds

• minor ear anomalies

• low nasal bridge

• micrognathia

what is micrognathia

micrognathia is a condition where the lower jaw is undersized or recessed

what are epichantha folds

Epicanthal folds are skin folds of the upper eyelid that cover the inner corner of the eye, while

what are some minor physical anomalies of FASD

• railroad track ears

• altered palm creases

• clinodactyly

• shorter than avg height

what are some impaired developments of eye that are associated with FASD

• microphthalmia - small eye

• coloboma

• retinal dysplasia

what are some neurological features of FASD

• hearing speech language disorders

• developmental delay

• cognitive deficits

• fine motor deficitis

• behavioural and emotional disturbances

• hypoplasia of brain structures (brain stem, cerebellum)

what does the outcome of FASD depend on

• amount, frequency, duration and gestational timing of alcohol consumption

what are the mechanisms of FASD

• ethanol metabolism generates ROS

• acetaaldehyde competes with retinaldehyde for RALDH2 - lack of retinoic acid

• acetyl-coa modifies gene expression

• fetus has low ADH and CYP2e1 - cannot be metabolised

• overall affects survival and migration of cranial neural crest cells and retinoic acid depletion means lack of signalling in early embryogenesis and patterning of structures

what is retinoic acid important for in embryonic development

• central nervous sytem patterning

• neurall crest formation

• fin/limb bud development

• heart specification

how does retinoic acid act as a tetrinogen

• when given orally can cause defects

what defects can oral retinoic acid cause

• facial defects

• CNS defects

• heart defects

• imbs and digits

• thymus and kidneys