Exposure to low doses of formaldehyde during pregnancy suppresses the development of allergic lung inflammation in offspring.
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.
Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
Marília
M
Maiellaro
Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Matheus
M
Correa-Costa
Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Luana Beatriz
LB
Vitoretti
Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
João Antônio
JA
Gimenes Júnior
Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Niels Olsen Saraiva
NO
Câmara
Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Wothan
W
Tavares-de-Lima
Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
Sandra Helena Poliselli
SH
Farsky
Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil. Electronic address: adrilino@usp.br.
Adriana
A
Lino-dos-Santos-Franco
D000393:Air Pollutants / Q000633:toxicity; D000542:Alveolitis, Extrinsic Allergic / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control; D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D001724:Birth Weight / Q000187:drug effects; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D060467:Disease Resistance / Q000187:drug effects*; D005260:Female; D047109:Fetal Development / Q000187:drug effects; D005557:Formaldehyde / Q000008:administration & dosage* / Q000633:toxicity; D005786:Gene Expression Regulation / Q000187:drug effects; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D018811:Maternal Exposure / Q000009:adverse effects; D016877:Oxidants / Q000008:administration & dosage* / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar; D020545:Respiratory Mucosa / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D014132:Trachea / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D000393:Air Pollutants; D016207:Cytokines; D016877:Oxidants; D005557:Formaldehyde
Anaphylactic antibodies synthesis; Asthma; Cytokines; Oxidative stress; Pollutants; Programming mechanisms