Oral or Poster Presentation
Concurrent Session 2C - DOHaD
Introduction: Bisphenol-A (BPA) is a commonly used plasticizer detected in the urine of 93% of US adults and associated with metabolic and cardiovascular diseases. Amid growing consumer concern, manufacturers turned to Bisphenol-S (BPS); however, its safety was unknown before introduction to market and thus, exposure to BPS is on rise. Since bisphenols cross placenta, they are likely to impact fetal development. Our aim is to determine the impact of BPS exposure on developmental adipogenesis, a key developmental event that starts in utero.
Methods: Stromal vascular fraction (SVF) was isolated from inguinal subcutaneous adipose tissue of juvenile male C56BL/6 mice and cultured with preadipocyte growth medium. The cells were treated with vehicle or variable doses of BPS [2.5nM (levels in drinking water); 250nM (permissible limit); 25µM]. A subset of cells were co-treated with DNMT-inhibitor (5-Aza-2'-deoxycytidine) and Estrogen receptor (ER)-1 and 2 inhibitors MPP and PHTPP respectively. At 48-hours post-confluency (contact-inhibition), cells were incubated with differentiation medium. At day 4 and 7 of differentiation, Oil Red-O staining was used to measure lipid droplet formation and mRNA expression of adipogenic genes was determined.
Results: At day 4 and day 7 of differentiation, lipid droplet formation, was increased in BPS-treated cells (p<0.001). BPS-induced pro-adipogenic response was biphasic with attenuated adipogenesis at highest dose. Expression levels of adipogenic mediators (PPAR-γ, SCD-1, GLUT-4 and SREBP-1) in differentiated cells and DNMT-3a and ZFP-423 (early adipogenic marker) in undifferentiated cells at contact-inhibition, were significantly higher in BPS treated cells (p<0.05). BPS-induced adipogenesis was abolished following DNMT-inhibitor treatment (p<0.001). ER-1 attenuated adipogenesis at later stages of differentiation.
Conclusion: Adipogenic potential is enhanced in preadipocytes exposed to BPS at doses lower than permissible limit and is regulated by DNA methylation. Studies are underway to determine the effect of maternal BPS exposure on developmental adipogenesis and explore DNA methylation as a potential mediator.