Poster Presentation The International Congress of Neuroendocrinology 2014

Obesity during pregnancy alters Fetal Immune responses and Hypothalamic Astrocytes in the mouse (#162)

Thomas Kim 1 , Kelly A Glendining 1 , Dave R Grattan 1 , Christine L Jasoni 1
  1. University of Otago, Dunedin, NZ, New Zealand

Maternal obesity during pregnancy is associated with chronic inflammation and elevates risk for offspring obesity. The hypothalamus regulates body weight, and hypothalamic glial cells in the adult mediate inflammatory response in obesity. Further, generation of glial cells (gliogenesis) is initiated during the fetal period and partly mediated by gp130 cytokines. Given that obesity induces inflammation and gliogenesis begins before birth, we examined whether maternal obesity would affect inflammation and/or alter glial development in the fetus. We focused on looking at the changes in the fetal cytokine levels and glial cells at two different ages (GD15.5 and GD17.5) in mice from normal weight (control) and a high-fat diet fed (HF) obese mothers. These two gestational ages represent the onset of gliogenesis from glial progenitors (GD15.5), and during gliogenesis (GD17.5) in mouse fetus. Multiplex cytokine analysis showed elevation of circulating cytokines in blood plasma of obese dams at both gestational ages (IL1b, IL6, IL10, IFNy, TNFa and IL17A). In HF fetus, elevation of circulating cytokines (IL6, IFNy and IL17A) was shown at GD17.5 only.

With altered fetal immune responses in HF group, we examined possible changes in glial cells - specifically hypothalamic astrocytes and microglia - in the fetal brains by using qPCR, flow cytometry and immunohistochemistry. Astrocytes were detected with GFAP expression at GD17.5, and astrocytes in the fetal supraoptic and arcuate nuclei of the hypothalamus showed significantly increased GFAP expression in maternal obesity compared to control. By contrast, only a small number of microglia were present in the fetal hypothalamus at these ages, and neither mRNA, cell number nor morphology was altered by maternal obesity. These data indicate that maternal obesity elevates fetal inflammation and alters the development and/or reativity of the hypothalamic astrocytes. Whether there is a causative link between the two remains for further study.