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

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.

Assessment of recent developmental immunotoxicity studies with bisphenol A in the context of the 2015 EFSA t-TDI

“…During the workshop, the participants considered that the two key studies performed by Ménard and colleagues needed further evaluation based on the identified immune effects at low BPA dosages (10, 11). At the workshop, these experimental studies were presented in detail by one of the authors Dr. Laurence Guzylack from INRA (Institut National de la Recherche Agronomique).…”

“…Two manuscripts by Ménard et al (2014) (10, 11), that were published after the closure date of the literature search for the 2015 EFSA opinion, reported on immune effects of pre- and postnatal developmental low dose exposure to BPA on oral tolerance and immunization to OVA (10, 11) and on host resistance to infection with an intestinal parasite (11) in rats. Oral tolerance induction is a tightly regulated immunological process that takes place in the gut-associated lymphoid tissue.…”

Prenatal exposure to bisphenol-A is associated with Toll-like receptor–induced cytokine suppression in neonates

“…Thus, it is possible that the extent of cytokine suppression exposed to low and environmentally relevant BPA level, such as in our study, was not sufficient to significantly increase the risk of infection or nasopharyngeal bacterial colonization in infants. Third, the few available data that suggest certain pollutants to increase susceptibility to infection were mostly results from animal studies or exposure to environmental toxin other than BPA (such as dioxins, cigarette smoke, diesel exhaust, and other air pollutants) (30,31). To our knowledge, only two published studies implied BPA exposure to increase the risk of infectious diseases in the pediatric population.…”

Early life exposure to bisphenol A investigated in mouse models of airway allergy, food allergy and oral tolerance

“…The risk of human adverse effects of BPA exposure has recently been critically reviewed by the European Food Safety Authority (EFSA), concluding with a lowering of the recommended tolerable daily intake level of 50 mg/kg body weight per day to 5 mg/kg body weight per day (EFSA, 2015). Recent studies report immune effects at BPA levels at or below this exposure level, supporting the need for further insight into adverse immune effects of BPA (Menard et al, 2014a(Menard et al, , 2014b.…”