Chapter 14. Environmental Effects on Development

Effects of Environmental Factors on Development

Introduction to Teratogens

  • Definition: Teratogens are factors originating from outside the embryo and mother that can cause birth defects.
  • Critical period: Susceptibility to teratogens is highest from fertilization through week 8 of pregnancy.

Types of Teratogens

  • Common teratogens include:
    • Medications
    • Heavy metals
    • Chemicals from industrial and agricultural activities

Specific Teratogen Examples

  • Heavy Metals:

    • Lead and mercury can damage the developing nervous system.
    • Bioaccumulation in fish, particularly carnivorous, long-lived species like swordfish, which should be avoided during pregnancy.

  • Endocrine Disruptors:

    • Affect hormone function and can lead to serious physical effects not as obvious as genetic abnormalities.
    • Medications and chemicals may act as endocrine disruptors affecting fetal development.

Historical Example: Diethylstilbestrol (DES)

  • A synthetic estrogen prescribed to pregnant women from 1940s to 1970s to prevent miscarriage.
  • Exposure led to significant adverse effects:
    • Over 4 million fetuses exposed in the US.
    • Caused reproductive system abnormalities in offspring, particularly:
    • Females: Vaginal/cervical cancer, reproductive tract abnormalities, T-shaped cervix.
    • Males: Genital tract abnormalities.

Effects of DES Exposure

  • Females:
    • Adenosis of cervix/vagina leading to abnormal tissue development.
    • Increased risks of ectopic pregnancy and cervical dysplasia.
  • Mechanism: DES mimics estrogen affecting the Müllerian duct development controlled by Hox genes (Hoxa-9, Hoxa-10, etc.).

Hox Gene Expression and Development

  • Normal expression patterns of Hox genes determine reproductive tract development:
    • Hoxa-9, Hoxa-10, Hoxa-11, Hoxa-13 influence junctions between reproductive organs.
    • Exposure to DES may repress these genes, causing abnormal junctions and structures (e.g., Hoxa-10 knockout mice show similar anomalies).

Other Endocrine Disruptors: Bisphenol A (BPA)

  • Used in various consumer products (plastics, food can linings).
  • Acts on estrogen receptors differently than natural estrogens:
    • May inhibit androgen receptor activity (testosterone).
  • Effects observed in female mice:
    • Changes in uterus, ovaries, and increased sensitivity to estrogen leading to higher cancer risks.
  • In male mice, BPA exposure led to low sperm counts and altered gene methylation patterns.

Endocrine Disruptors and Fertility

  • Associated with reduced fertility in both genders:
    • Women:
    • Issues with cycle length, oocyte quality, and response to stimulation – linked to pesticides and PCBs.
    • Men:
    • Affects sperm motility and morphology, DNA integrity, leading to lower sperm counts and fertilization issues.
  • Global Trends: Studies show declining sperm counts since the 1970s in humans and dogs.

Impact of Endocrine Disruptors on Obesity

  • Prenatal exposure to endocrine disruptors can lead to increased fat cell production in genetically identical mice.
  • Mechanisms:
    • Activating PPARg transcription factor, promoting stem cells to become adipocytes instead of chondrocytes or osteoblasts.
    • Encouraging fat synthesis and storage in the liver.