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  • Introduction

  • The Reproductive Cycle

  • Reproductive Development and Sexual Differentiation

  • Gametogenesis

  • Neonatal Development

  • Infantile Development

  • Pubertal Development

    • Rodent Models of Puberty

      • Selected Examples of Chemicals That Alter the Onset of Pubertal Landmarks in Rats After Acute In Utero and/or Lactational Exposures

      • Selected Examples of Chemicals That Alter the Onset of Pubertal Landmarks in Rats After Peripubertal Exposures

  • Sexual Maturity

    • Hypothalamic–Pituitary–Gonadal Axis

    • Ovarian Function

      • Oogenesis

      • Case Study—Busulfan

    • Ovarian Cycle

    • Postovarian Processes

      • Oviducts

      • Uterus

  • Testicular Structure and Function

    • Targets for Toxicity

    • Testicular Structure and Spermatogenesis

    • Posttesticular Processes

    • Erection and Ejaculation

    • Case Studies for Effects on the Male

      • m-Dinitrobenzene

      • Ethylene Glycol Monomethyl Ether

  • Mating Behavior in the Rat

    • Cervix

    • Vagina

  • Fertilization

  • Implantation

  • Placenta

  • Pregnancy

  • Parturition

  • Lactation

  • Senescence

  • Endocrine Disruption (Including Screening and Puberty)

    • Known Effects of EDCs in Humans and Animals

      • Effects of Drugs on Human Sexual Differentiation

      • Effects of Plant and Fungal Products in Animals and Humans

      • Effects of Organochlorine Compounds in Humans

      • Occupational Exposures

    • Environmental Androgens

    • Environmental Antiandrogens

      • Fungicides

      • Linuron (Herbicide)

      • p,p′-DDE (Pesticide Metabolite)

      • Phthalates (Plasticizers)

    • Environmental Estrogens

    • EDC Screening Programs

      • In Vivo Mammalian Assays

      • Alternative Screening Assays

  • Testing for Reproductive Toxicity

    • Screens and Multigeneration Studies

    • Testing for Endocrine Disrupting Chemicals

      • Developmental Syndromes and Tailored Testing

      • Test Design and Numbers of F1 Animals

    • Testing Pharmaceuticals

    • Newer Guidelines and Approaches

  • Evaluation of Toxicity to Reproduction

    • Concordance of End Points

    • Consistency Across Generations

    • Graded Effects

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Introduction

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Any evaluation of toxicity to reproduction will have as an important consideration that events may not only be on the adults having impact on their likelihood to have children, but also impact the viability and quality of life of their potential offspring and feasibly even affect later generations. That chemicals can adversely affect reproduction in males and females is not a new concept, one only has to look at the importance of drugs as contraceptives to realize how sensitive the reproductive system can be to external chemical influences to disrupt this process. Of course in these cases, the failure of normal reproduction is a desired outcome in a contraceptive, but unfortunately we have had a number of catastrophes in which such failure has been unintentional. Many of the classic examples in chemical workers, or contamination of groundwater from chemical exposure such as dibromochloropropane (DBCP) or kepone (chlordecone) have shown the sensitivity of human reproduction to these specific exposures (reviewed by Cannon et al., 1978; Faroon et al., 1995; Winker and Rudiger, 2006). There have been significant improvements in our ability to test for effects on reproduction for chemicals, agrochemicals, and drugs, but unfortunately such adverse episodes continue to occur in, for example, the more recent reports of the effects of 2-bromopropane in chemical workers (both male and female) in Korea (reviewed by Boekelheide et al., 2004).

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Recent trends in human fertility, fecundity—changing social influences (age at which women have their first child), and the knowledge that populations in many western countries are no longer self-sustaining, coupled with the advent of assisted ...

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