Increases in a diversity of childhood and adult diseases (eg, autism, behavioral/learning abnormalities, obesity) have been attributed, in part, to programming effects resulting from developmental nutrient and chemical exposures. Bisphenol A (BPA) is a ubiquitous chemical widely used in plastics (e.g., water bottles, food can liners) and paper industries, and significant levels are consistently observed in pregnant women and fetal plasma and amniotic fluid. BPA acts an endocrine disrupter (EDC), and epidemiological studies confirm that EDC exposure during developmental periods may impact stem cell growth and development, and hence the ultimate make-up of organs, cell populations, and cell signaling/function. Consistent with this premise, studies have shown that EDCs alter neurogenesis of adult neural progenitor cells (NPC). Despite the array of EDC-induced cognitive and behavioral effects, there has been scant data of the effects of EDCs on fetal NPC proliferation and differentiation, functions which are critical for brain development. We have confirmed that offspring of both obese, overnourished dams and BPA-exposed control dams develop early onset obesity. Utilizing a model of NPC, we have demonstrated a dose dependent increase in NPC proliferation with increased expression of Hes1 (neuroproliferative factor), whereas in differentiation media, BPA increased Mash1 (proneurogenic factor), Tuj1 and GFAP (neuronal and astrocyte markers), and LSD1 (histone demethylase). We propose that maternal BPA exposure acts additively or synergistically with maternal obesity to alter hypothalamic development, resulting in an increase in appetite versus satiety neurons. Using both NPC neurosphere culture and in vivo/ex vivo rodent studies, this proposal provides a unique opportunity to determine mechanisms of programmed hyperphagia in BPA-exposed offspring which contribute to offspring obesity.
During developmental periods, exposure to altered nutrition or environmental chemicals increases the risk of childhood and adult diseases (eg, autism, behavioral/learning abnormalities, obesity). In particular maternal obesity and bisphenol A (BPA, chemical widely used in plastics) causes offspring obesity, partly as a result of increased feeding. The proposed studies will use neural stem cells to investigate how maternal obesity combined with BPA favor increased appetite and suppress satiety neurons in the offspring.
| Desai, M; Ferrini, M G; Jellyman, J K et al. (2018) In vivo and in vitro bisphenol A exposure effects on adiposity. J Dev Orig Health Dis :1-10 |
| Galyon, Kristina D; Farshidi, Farnoosh; Han, Guang et al. (2017) Maternal bisphenol A exposure alters rat offspring hepatic and skeletal muscle insulin signaling protein abundance. Am J Obstet Gynecol 216:290.e1-290.e9 |
| Desai, Mina; Han, Guang; Ross, Michael G (2016) Programmed hyperphagia in offspring of obese dams: Altered expression of hypothalamic nutrient sensors, neurogenic factors and epigenetic modulators. Appetite 99:193-199 |
