IN-VITRO EFFECTS OF BISPHENOL A, BENZOPHENONES 2 AND 3 ON CYTOKINE EXPRESSION IN WHOLE HYPOTHALAMI AND IMMORTALIZED GNRH NEURONS

RIAÑO GÓMEZ, JUAN MANUEL ; LIBERTUN C; MARIGLIANO, CAMILA; LUX-LANTOS, VICTORIA; SORIANELLO, ELEONORA; FERNANDEZ, MARINA OLGA

Mar del Plata

Congreso; Reunión Anual SAIC - SAFE - SAB - SAP - AACyTAL 2019; 2019

Sociedad Argentina de Investigación Clínica - SAIC

Bisphenol A (BPA), a monomer of polycarbonate plastics, and Benzophenones (BPs), UV-filters, are endocrine disrupting chemicals (EDC). The hypothesis is that EDC exposure causes brain inflammation and predisposes animals to develop obesity and infertility. Previous results showed that the in-vitro exposure to BPA increases Glial Fibrillary Acidic Protein (GFAP) in hypothalami and IL-18 in mature GnRH neurons. Here, gene expression of cytokines (interleukins 6 and 1ß, IL-6 and IL-1ß) were evaluated in whole hypothalami of adult Balb/c mice and in immortalized GnRH neurons. Hypothalami were incubated in Krebs-Ringer medium in the presence or absence of BPA, BP2 or BP3 (1x10-9 M) or medium alone (C) for six hours, and mRNA was extracted for gene expression analysis by qPCR. GnRH neuronal cell lines were cultured in 12-well plates (200,000 cells/well) in DMEM supplemented with 10 % FBS. After 24 hours, media were changed to DMEM without phenol red with 10% charcoal-stripped FBS. Cells were incubated with BPA, BP2, BP3 (1x10-9 M) or vehicle (C) for 12 or 24 hours, RNA was extracted and gene expression analyzed by qPCR. In the hypothalami, IL-1ß expression was not changed by EDC exposure (ANOVA ns, n=8). Exposure to BP2 decreased IL-6 compared to C, although not reaching statistical significance (C= 1.1 ± 0.3; BP2= 0.5 ± 0.2; C vs. BP2, p= 0.08, n= 8). Neither BPA nor BP3 changed IL-6 expression. In GT1-7 cells (mature GnRH neurons), 24-hour exposure to BPA decreased IL-6 expression, without reaching statistical significance (C= 1.1 ± 0.2; BPA= 0.7 ± 0.1, C vs. BPA, p= 0.09, n= 4). Neither BP2 nor BP3 changed IL-6 in this cell line. Further experiments are underway to confirm the gene expression changes. The results will help us to further understand how exposure to EDC affects brain inflammation.Supported by CONICET, ANPCyT, UBA, Int. Soc. for Neurochemistry, Asoc. ORT Argentina, Fund. René Barón and Fund. Williams grants.