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Extent of the Problem

Extent of the Problem. Approximately 10% of couples are infertile. Nearly half of all pregnancies do not result in the birth of a normal child. One in 33 babies is born with a major birth defect. An additional 15-25% of babies have minor defects or functional defects.

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Extent of the Problem

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  1. Extent of the Problem • Approximately 10% of couples are infertile. • Nearly half of all pregnancies do not result in the birth of a normal child. • One in 33 babies is born with a major birth defect. • An additional 15-25% of babies have minor defects or functional defects. • The effects of environmental agents are largely unknown, but may have some interaction with 3-50% of birth defects.

  2. Causes of Reproductive Toxicity • Inhibition of spermatogenesis or oogenesis, maturation or motility. • Hormonal imbalance • Behavioral toxicity • Developmental toxicity

  3. Male Reproductive Toxicity • Male germ cells are continuously produced, but take weeks to mature. • Toxicity to a single stage of developing sperm will only be picked up if breeding is followed over the period of maturation. • The number of sperm in rodents is much greater than in humans. Rodents can successfully breed with 70-90% decreases in sperm. • Humans have much less reserve and can suffer from infertility with smaller decreases,

  4. EPIDIDYMIS TRANSPORT STORAGE MATURATION MOTILITY FERTILIZING ABILITY NORMAL DEVELOPMENT

  5. Female Reproductive Toxicity • Females have all their germ cells at birth. • The ovulatory cycle is under hypothalamic control. • Reproductive senescence in humans arises from a lack of oocytes, whereas in rodents it is due to hypothalamic-controlled constant estrus or pseudopregnancy.

  6. Reproductive Toxicity • Chemicals and drugs are tested for their ability to cause reproductive or developmental toxicity. • Segment I: Tests for effects on fertilization and implantation • Segment II: Evaluates effects on developmental toxicity • Segment III: Evaluates effects on parturation, birth, lactation and early development • Two Generation Study • Evaluates fertilization through early development of two generations

  7. Developmental Toxicology • Altered survival (death) • Prenatal • Postnatal • Morphological alterations • Malformations • Variations • Developmental delays • Growth • Skeletal development • Neurodevelopment • Acquisition of developmental landmarks • Functional deficits • Biochemical • Sexual development • Behaviorial

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