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.
Causes of Reproductive Toxicity Inhibition of spermatogenesis or oogenesis, maturation or motility. Hormonal imbalance Behavioral toxicity Developmental toxicity
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,
EPIDIDYMIS TRANSPORT STORAGE MATURATION MOTILITY FERTILIZING ABILITY NORMAL DEVELOPMENT
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.
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
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