Prenatal Exposure to Bisphenol A and Diethylhexyl Phthalate Induces Apoptosis in the Thymus of Male and Female Offspring

Abstract

Bisphenol A (BPA) and Diethylhexyl Phthalate (DEHP) are common environmental endocrine disrupting chemicals (EDCs) that exert a range of potential adverse health effects. EDC exposure can occur in utero and during early postnatal life, when organ systems are differentiating resulting in a number of disorders in adulthood. The aim of this study was to evaluate the immunotoxic effect of prenatal exposure to individual and combinations of BPA and DEHP on male and female rat thymus. From gestational day 6 till 21, Sprague Dawley dams were orally administered either saline (control; n=7), BPA (5μg/Kg BW; n=7), DEHP (7.5mg/Kg BW; n=7), or a mixture of BPA and DEHP (B+D; n=7). Male and female offspring were sacrificed at 16 weeks of age. Thymus and spleen were dissected, weighed, and stored for further processing. Our data showed that spleen weight to body weight (BW) ratio of EDC treated offspring were comparable to those from age‐matched control rats. However, male offspring (but not females) that were prenatally exposed to BPA alone exhibited a 40% decrease (p<0.01) and those exposed to DEHP alone had a 27% reduction in thymus/BW ratio (p<0.05). To understand if prenatal EDC exposure was promoting early thymus involution through apoptosis, we performed Terminal deoxynucleotidyl transferase‐dUTP nick end labeling (TUNEL) staining of nicked DNA on thymic sections. There was significant apoptosis in the thymic cortex in both male and female offspring that were prenatally exposed to individual EDCs. Apoptosis was hardly detected in the medullary region. Apoptosis in the B+D group was markedly reduced compared to individual EDC exposures. These results suggest that prenatal exposure to even low BPA and moderate DEHP levels can promote apoptosis in the thymus. This could possibly affect immune functions in adulthood. Interestingly, exposure to a mixture of these EDCs did not produce any significant change in apoptosis in the thymus.Support or Funding InformationSupported by UGA Research Foundation and start‐up funds.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Six Decades of Dopamine Hypothesis: Is Aryl Hydrocarbon Receptor the New D2?

“…Translocation of Hafnei alvei, Pseudomonas aeruginosa, Morganella morganii, Pseudomonas putida, and Klebsiella pneumoniae [12][13][14] Comorbidity with IBD AhR/STAT3/IL-22-regulated intestinal permeability and microbiota translocation [11,15,16] Comorbidity with HIV AhR/STAT3/IL22-regulateted gut barrier permeability [12,17,18] Poor insight (anosognosia) IC activation by gut Prevotella and Bacteroides abundance [19][20][21][22][23][24][25] Higher prevalence in urban areas Pollutants are AhR ligands associated with SCZ and are more prevalent in industrialized countries and urban areas [26][27][28][29][30][31][32][33][34] Increasing prevalence with the distance from the equator Sunlight-driven vitamin D derivatives and tryptophan light metabolites are AhR ligands [35][36][37][38][39] Autoantibodies Gut microbes express molecules, including GABA and NMDA, which can elicit formation of antibodies upon translocation [40][41][42] Aryl hydrocarbon receptor (AhR), a cytosolic transcription factor, initially described as the dioxin receptor, responds to numerous exogenous and endogenous ligands, inducing both immune tolerance of gut microbes as well as their prompt elimination upon translocation into host tissues [43,44]. In the cytosol, AhR is bound by two heat shock protein 90 (HSP90) chaperones, molecules recently identified as both SCZ and Parkinson's disease (PD) targets [45][46]…”

“…Environmental pollutants, including dioxin, bind with high affinity to AhR, inducing neuronal apoptosis and cognitive dysfunction. For example, prenatal exposure to diethylhexyl phthalate (DEHP), a widely used plasticizer, has been shown to disrupt the thymus, inducing premature involution of this gland, a pathology encountered in SCZ [29,30,199,200]. In addition, this pollutant triggers gut barrier disruption and was linked to autism spectrum disorder (ASD), suggesting likely involvement in SCZ [31,32].…”