An in vivo model for human fetal adipose tissue development

Abstract

Adipogenesis in the developing fetus is a key determinant of postnatal adiposity and, by extension, the risk of developing obesity‐related disease later in life. A variety of environmental factors, including toxicants and maternal diet, can influence fetal adipogenesis. To study the effects of environmental factors on fetal adipogenesis, we have developed a xenotransplantation model. Mid‐gestation human fetal white adipose tissue (WAT), obtained from cases of spontaneous fetal loss, was implanted into immunocompromised rodents using the renal subcapsular site. In multiple experiments (7 fetal samples ranging in gestation from 20 to 22 weeks), we observed an initial loss of adipocytes within the first week. This was followed by development of obvious fat pads. Expansion of these fat pads continued for up to 6 months. Immunohistochemical analyses revealed the WAT foci to contain viable adipocytes that were heterogeneous in size, an indication of active adipogenesis. Staining for the endothelial cell marker CD31 demonstrated rich vascularity of the implants and invasion of vessels from the implant into the host kidney parenchyma. These results demonstrate that transplantation of human fetal WAT into immunocompromised mice is a model for marked healthy WAT expansion and remodeling. This model can be utilized to study the direct effect of nutrient manipulation and obesogens on fetal white adipose tissue.