Perinatal Exposure to a Low Dose of Bisphenol A Impaired Systemic Cellular Immune Response and Predisposes Young Rats to Intestinal Parasitic Infection

PLoS One. 2014 Nov 21;9(11):e112752. doi: 10.1371/journal.pone.0112752. eCollection 2014.

Abstract

Perinatal exposure to the food contaminant bisphenol A (BPA) in rats induces long lasting adverse effects on intestinal immune homeostasis. This study was aimed at examining the immune response to dietary antigens and the clearance of parasites in young rats at the end of perinatal exposure to a low dose of BPA. Female rats were fed with BPA [5 µg/kg of body weight/day] or vehicle from gestational day 15 to pup weaning. Juvenile female offspring (day (D)25) were used to analyze immune cell populations, humoral and cellular responses after oral tolerance or immunization protocol to ovalbumin (OVA), and susceptibility to infection by the intestinal nematode Nippostrongylus brasiliensis (N. brasiliensis). Anti-OVA IgG titers following either oral tolerance or immunization were not affected after BPA perinatal exposure, while a sharp decrease in OVA-induced IFNγ secretion occurred in spleen and mesenteric lymph nodes (MLN) of OVA-immunized rats. These results are consistent with a decreased number of helper T cells, regulatory T cells and dendritic cells in spleen and MLN of BPA-exposed rats. The lack of cellular response to antigens questioned the ability of BPA-exposed rats to clear intestinal infections. A 1.5-fold increase in N. brasiliensis living larvae was observed in the intestine of BPA-exposed rats compared to controls due to an inappropriate Th1/Th2 cytokine production in infected jejunal tissues. These results show that perinatal BPA exposure impairs cellular response to food antigens, and increases susceptibility to intestinal parasitic infection in the juveniles. This emphasized the maturing immune system during perinatal period highly sensitive to low dose exposure to BPA, altering innate and adaptative immune response capacities in early life.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzhydryl Compounds / administration & dosage
  • Benzhydryl Compounds / pharmacology*
  • Dose-Response Relationship, Drug
  • Female
  • Immunity, Cellular / drug effects*
  • Intestinal Diseases, Parasitic / immunology*
  • Maternal Exposure*
  • Phenols / administration & dosage
  • Phenols / pharmacology*
  • Pregnancy
  • Rats
  • Rats, Wistar

Substances

  • Benzhydryl Compounds
  • Phenols
  • bisphenol A

Grant support

This work was supported by grant ANR-10-CESA-005 from Agence Nationale de la Recherche (http://www.agence-nationale-recherche.fr/) (France) and AP AlimH 2008 from Institut National de la Recherche Agronomique (http://www.alimh.inra.fr/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.