Mechanism of teratogenesis

Teratogen is an exogenous agent (radiation, chemicals, biological agents, nutritional deficiencies and other environmental factors) or endogenous (metabolites produced in excess by the mother, fetus or both) that has the ability to produce during development and fetal malformations embrionrio congenital or functional defects. Mechanisms of teratogenesis

It has 3 stages: causes, mechanisms and manifestations

Causes • present throughout the environment • Act directly or indirectly on germ cel, embryos or fetuses, altering one or more core development processes (eg cell population migrations, organogenesis, cell differentiation and cell multiplication) • Radiation chemicals, infections, hypoxia, physical trauma and drugs

• Feedback mechanisms in the embryo • nondisjunction chromosomal mutations, lack of precursors or substrates, enzyme inhibition • Energy sources and cell membrane altered altered

Manifestations • cell death, failure of cellular interactions, reduced biosynthesis prevented • morphogenetic movement, abnormal tissue and altered differentiation processes target sites of action for teratogens I. Basic processes of development (regulation of cell growth, expression of specific genes) II. Abnormalities cause (pathogenesis) that represent demonstrable aspects (manifestations) of teratogenesis: • Interference mitotic disruption of the integrity of DNA and RNA • cell death, loss of cellular interactions, hampering movement mofogenético • Intrauterine death, malformation, retarded growth and functional deficiencies (enzyme inhibition) or both human teratogenicity I. Physical • Dose Ionizing radiation equal to or greater than 30 rads • Generate de novo mutations in germ cells and somatic alterations in the M phase of cell cycle by reducing the mitotic index , cell death, replacement and cell growth delay and fragmentation of chromosomes caused by chemical changes in DNA • UV light, X rays, gamma rays, protons, neutrons, α particles and other atomic particles can cause chromosomal breakage • Microcephaly, abnormal eye, mental retardation and CNS anomalís

II. Hyperthermia • • Fever 38.9 ° C in the first quarter can be linked to neural tube defects and dysmorphic syndromes • (We recommend using hot bath temperature not exceeding 40 ° C for more than 10 minutes during the 1st quarter) Chemical

CNS and organs, especially the first 8 weeks after conception

• Thalidomide Sedative, hypnotic and antiemetic treatment for patients with leprosy and AIDS • Interaction with the metabolism of a. Folic interaction with the synthesis of a. nucleic immune suppression and inhibition of oxidative phosphorylation • Provides primary action in the PNS (Altered tissue growth depends on the development of sensory neurons - malformations)

Diethylstilbestrol (DES) • Estrogen vs threatened abortion and premature delivery • causal agent of clear cell adenocarcinoma of the vagina and cervix and vaginal adenosis

? Retinoic acid • At low doses is teratogenic • Between the 3rd and 5th week of pregnancy causes various mC • Changes in craniofacial cleft paladr, neural tube defects, cardiovascular malformations and thymus aplasia • Their receptors bind to regulatory sequences DNA

? Anticonvulsant valproic acid • • cause spina bifida and encephalocele • Responsible for valproic acid embryopathy • spina bifida, prominent forehead, hypoplastic facial middle ear malformations and growth retardation posnaal • Altera folate metabolism

• methotrexate folic acid antagonist, acts on dihydrofolate redactasa during the synthesis of thymidylate • In adults, used to control cell division characteristic of chaotic most of the tumors or ectopic pregnancy.

Coumarin anticoagulant therapy • • critical period of exposure is between the 6th and 9th week • craniofacial growth abnormalities, microcephaly, hypoplasia of the central area of ​​the face with nasal hypoplasia • Optic atrophy, corneal opacities, cataracts and other eye defects • Skeletal Abnormalities malformations of the CNS midline, intrauterine growth retardation and mental retardation Biological tend to produce clinical manifestations not apparent in the host to enable early diagnosis and prompt medical intervention

Rubella • During the first quarter: cataracts, microcephaly, heart defects and deafness • direct viral effect and altered immune response • Inhibit normal cell division, so altered organogenesis

Cytomegalovirus • In the early stages of pregnancy is often lethal • In later stages can cause blindness, deafness and mental retardation may go unnoticed • 90% of the time, 5% have: • Hepatitis, microcephaly, eye disorders, anemia, calcified intracranial and intrauterine growth retardation • causes cell lysis and altered immune response

Toxoplasma gondii • During the 1st trimester of pregnancy causes severe manifestations • During Q2 = major malformations • Hydrocephalus, microphthalmia, brain injuries, intracranial calcifications and multiple organ damage • Dependent Diabetes Disease maternal insulin or poorly controlled type 1 cause: • Congenital heart disease, skeletal, CNS disturbances and causal sequence regression • altered metabolism of carbohydrates cause perinatal death

Epilepsy • Seizures cause fetal hypoxia and intrauterine growth retardation • microcephaly, mental retardation and growth, cleft lip and palate, cardiac abnormalities, spina bíficda, strabismus, muscular hypotonia and ptosis • is not yet known if the disease or treatment that causes these malformations

Hypertension • intrauterine growth restriction, placental abruption and fetal distress in Q3 • A decrease in oxygen supply to the uterus, fetal hypoxia caused social Exposure Alcohol • Causes physical and mental defects at birth • Alcohol crosses the placenta and enters the fetal circulatory system, causing constriction of blood vessels and inducing fetal hypoxia and malnutrition • Alcohol embryopathy syndrome: a. intrauterine growth retardation, delayed physical and mental development. Vascular, small palpebral fissures, microcephaly and microphthalmia • During lactation: b. take longer to acquire motor skills than non expuestosc. Ingestion of large amounts of alcohol can interfere with milk secretion Cocaine • First trimester is associated with myocardial the fetus due to vascular insufficiency), intestinal perforation with ileal atresia, abnormal placenta and lower extremities with absence of toes, spontaneous abortions, premature births, intrauterine growth retardation and microcephaly.