Exposure to low doses of formaldehyde during pregnancy suppresses the development of allergic lung inflammation in offspring

Toxicol Appl Pharmacol. 2014 Aug 1;278(3):266-74. doi: 10.1016/j.taap.2014.05.003. Epub 2014 May 15.

Abstract

Formaldehyde (FA) is an environmental and occupational pollutant, and its toxic effects on the immune system have been shown. Nevertheless, no data are available regarding the programming mechanisms after FA exposure and its repercussions for the immune systems of offspring. In this study, our objective was to investigate the effects of low-dose exposure of FA on pregnant rats and its repercussion for the development of allergic lung inflammation in offspring. Pregnant Wistar rats were assigned in 3 groups: P (rats exposed to FA (0.75 ppm, 1 h/day, 5 days/week, for 21 days)), C (rats exposed to vehicle of FA (distillated water)) and B (rats non-manipulated). After 30 days of age, the offspring was sensitised with ovalbumin (OVA)-alum and challenged with aerosolized OVA (1%, 15 min, 3 days). After 24 h the OVA challenge the parameters were evaluated. Our data showed that low-dose exposure to FA during pregnancy induced low birth weight and suppressed the development of allergic lung inflammation and tracheal hyperresponsiveness in offspring by mechanisms mediated by reduced anaphylactic antibodies synthesis, IL-6 and TNF-alpha secretion. Elevated levels of IL-10 were found. Any systemic alteration was detected in the exposed pregnant rats, although oxidative stress in the uterine environment was evident at the moment of the delivery based on elevated COX-1 expression and reduced cNOS and SOD-2 in the uterus. Therefore, we show the putative programming mechanisms induced by FA on the immune system for the first time and the mechanisms involved may be related to oxidative stress in the foetal microenvironment.

Keywords: Anaphylactic antibodies synthesis; Asthma; Cytokines; Oxidative stress; Pollutants; Programming mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Air Pollutants / toxicity
  • Alveolitis, Extrinsic Allergic / chemically induced
  • Alveolitis, Extrinsic Allergic / immunology*
  • Alveolitis, Extrinsic Allergic / metabolism
  • Alveolitis, Extrinsic Allergic / prevention & control
  • Animals
  • Asthma / chemically induced
  • Asthma / immunology
  • Asthma / metabolism
  • Asthma / prevention & control
  • Birth Weight / drug effects
  • Cytokines / genetics
  • Cytokines / metabolism
  • Disease Models, Animal*
  • Disease Resistance / drug effects*
  • Female
  • Fetal Development / drug effects
  • Formaldehyde / administration & dosage*
  • Formaldehyde / toxicity
  • Gene Expression Regulation / drug effects
  • Lung / drug effects*
  • Lung / immunology
  • Lung / metabolism
  • Maternal Exposure / adverse effects
  • Oxidants / administration & dosage*
  • Oxidants / toxicity
  • Oxidative Stress / drug effects
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Rats
  • Rats, Wistar
  • Respiratory Mucosa / drug effects
  • Respiratory Mucosa / immunology
  • Respiratory Mucosa / metabolism
  • Trachea / drug effects
  • Trachea / immunology
  • Trachea / metabolism

Substances

  • Air Pollutants
  • Cytokines
  • Oxidants
  • Formaldehyde