It is an important branch of toxicology. It studies the abnormal development outcomes and related mechanisms of development of developing organisms due to exposure to environmental harmful factors before birth during the development process of fertilized eggs, gestation, postnatal, and sexual maturity. Pathogenesis, influencing factors and toxicokinetics, etc.

Thalidomide incident

Malformation: refers to defects in the anatomy of a developing organism. Can have harmful effects on appearance, physiological functions and/or lifespan, and can lead to survival or death

teratogen

2.Mutation

3. Embryo body-fetal body toxicity

4. Developmental toxicity

Birth defect: refers to developmental disorders that occur before a baby is born, including deformities and functional defects. Such as congenital heart disease, cleft lip and palate, neural tube malformation, hypospadias, cryptorchidism, etc.

Adverse pregnancy outcomes (adverse pregnancy outcomes): refers to the failure of pregnancy to produce offspring with normal appearance and function.

Compared with the toxic effects on other organ systems, the developmental toxic effects of exogenous chemicals have significant characteristics:

(1) Developmental toxicity characteristics and teratogenic sensitive periods at various stages of development

(2) Dose-response model of developmental toxicity

(3) Species differences in developmental toxicity

Maternal toxicity: Refers to the damaging effects of exogenous chemicals on the pregnant mother at a certain dose. Specific manifestations include weight loss, the development of certain clinical symptoms, and death.

(1) The influence of maternal factors on developmental toxicity

(2) The relationship between maternal toxicity and embryo toxicity

More and more population epidemiological studies have found that certain birth defects are also related to male factors, known as paternal birth defects.

The main factors causing paternal birth defects are genetic defects, age factors and external exposure factors (including occupational and environmental exposures, chemotherapy and radiotherapy, other drugs, and bad habits such as drinking and smoking). These factors have adverse effects on the developing individual through the father. effects, hence the name paternal developmental toxicity

(1) Main manifestations of paternal developmental toxicity

(2) The relationship between paternal factors and developmental toxicity

1.Gene mutations and chromosomal aberrations

2. Cell damage and death

3. Interfering with cell-cell interactions

4. Causes developmental toxicity through placental toxicity

5. Disturb maternal homeostasis

6. Intrauterine reprogramming and embryonic developmental toxicity

1. Definition of reprogramming and intrauterine reprogramming

2. Epigenetic heritable changes in gene expression levels caused by non-DNA sequence changes

3. Early reprogramming of embryonic development

4. Intrauterine reprogramming and epigenetic related diseases such as obesity, hyperglycemia, cardiovascular diseases, and psychiatric and neurological diseases

Advantages: It is easy to control the contact conditions, the number, age, status of contact animals and select detection effect indicators (end points). Even minor effects are interesting for studying human effects

Disadvantages: There is uncertainty in the extrapolation of test results to humans, and the specificity of predicting teratogenicity in humans is not high enough; it is difficult to extrapolate from higher dose exposure results to humans (lower exposure dose), and there are also differences between humans individual differences are greater than those of animals

Three-stage toxicity test (textbook p209)

Use epidemiological methods to study the impact of reproductive toxicants in the environment on population reproduction and development, including the nature, extent and causes

Environmental epidemiological research must be coordinated with the detection of environmental chemical toxicants and the detection of human biomarkers, that is, molecular epidemiological research.

Environmental epidemiological research is not a general epidemiological investigation. It must be scientifically designed, strictly select objects and controls, and objectively quantify observation indicators.

Criteria for identification of human teratogens

In vivo primary screening test

In vitro preliminary screening test

Model organism preliminary screening test