Effects of in Utero Exposure to Arsenic during the Second Half of Gestation on Reproductive End Points and Metabolic Parameters in Female CD-1 Mice

Environ Health Perspect. 2016 Mar;124(3):336-43. doi: 10.1289/ehp.1509703. Epub 2015 Aug 21.


Background: Mice exposed to high levels of arsenic in utero have increased susceptibility to tumors such as hepatic and pulmonary carcinomas when they reach adulthood. However, the effects of in utero arsenic exposure on general physiological functions such as reproduction and metabolism remain unclear.

Objectives: We evaluated the effects of in utero exposure to inorganic arsenic at the U.S. Environmental Protection Agency (EPA) drinking water standard (10 ppb) and at tumor-inducing levels (42.5 ppm) on reproductive end points and metabolic parameters when the exposed females reached adulthood.

Methods: Pregnant CD-1 mice were exposed to sodium arsenite [none (control), 10 ppb, or 42.5 ppm] in drinking water from gestational day 10 to birth, the window of organ formation. At birth, exposed offspring were fostered to unexposed dams. We examined reproductive end points (age at vaginal opening, reproductive hormone levels, estrous cyclicity, and fertility) and metabolic parameters (body weight changes, hormone levels, body fat content, and glucose tolerance) in the exposed females when they reached adulthood.

Results: Arsenic-exposed females (10 ppb and 42.5 ppm) exhibited early onset of vaginal opening. Fertility was not affected when females were exposed to the 10-ppb dose. However, the number of litters per female was decreased in females exposed to 42.5 ppm of arsenic in utero. In both 10-ppb and 42.5-ppm groups, arsenic-exposed females had significantly greater body weight gain, body fat content, and glucose intolerance.

Conclusion: Our findings revealed unexpected effects of in utero exposure to arsenic: exposure to both a human-relevant low dose and a tumor-inducing level led to early onset of vaginal opening and to obesity in female CD-1 mice.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adipose Tissue / drug effects
  • Animals
  • Arsenites / toxicity*
  • Blood Glucose / metabolism
  • Drinking Water / chemistry
  • Environmental Pollutants / toxicity*
  • Estrous Cycle / drug effects
  • Female
  • Fertility / drug effects
  • Gonadotropins / blood
  • Mice
  • Pregnancy
  • Prenatal Exposure Delayed Effects / metabolism
  • Prenatal Exposure Delayed Effects / physiopathology
  • Reproduction / drug effects*
  • Sexual Maturation / drug effects*
  • Sodium Compounds / toxicity*
  • Vagina / drug effects
  • Vagina / physiology


  • Arsenites
  • Blood Glucose
  • Drinking Water
  • Environmental Pollutants
  • Gonadotropins
  • Sodium Compounds
  • sodium arsenite