宫内高雄激素环境诱导的巨噬细胞浸润对子代雌鼠脂肪组织重塑的影响及机制

Excess androgen in the intrauterine environment indeed exist in PCOS pregnant women ，and the risk of obesity in female offspring of PCOS was increased . Our previous studies found that female offspring of SD pregnant rats which were excess androgen in intrauterine environment were likely obesed, and androgen could enlarge the volume of adipocytes,which suggested that excess androgen in intrauterine environment may play a key role in PCOS offspring obesity, but the mechanism is not clear. The precursor of obesity is adipose tissue remodeling. The infiltration of macrophages and angiogenesis play a key role in this process. Our previous studies have found that excess androgen in the intrauterine environment can promote the transformation of macrophages in adipose tissue to pro-inflammatory M1 subtype. Therefore, we speculated that the intrauterine environment of excess androgen may promote the adipose tissue remodeling of the offspring by promoting the infiltration of macrophages and angiogenesis, which eventually leads to obesity.This study is designed 2 animal models of female offspring: ①transgenetic adipochaser mice ②neonatal SD rats by removal of macrophages with liposome, to investigate the effects of macrophage infiltration on adipose tissue remodeling and the expression of related molecules in excess androgen intrauterine environment, then we establish macrophage-adipocytes, macrophage-endothelial cell co-culture system under high dose of androgen individually, to furtherly investigate the role of macrophage in the obesity induced by androgen, So as to provide a theory basis to prevent PCOS offspring obesity.

多囊卵巢综合征（PCOS）孕妇存在宫内高雄环境，且其子代肥胖风险显著增加。我们前期研究证实暴露于宫内高雄环境的子代SD雌鼠出现肥胖，且睾酮能促进脂肪细胞体积异常增大，提示宫内高雄可能诱导子代肥胖，但机制未明。肥胖的前驱表现为脂肪组织重塑，而形成后者的关键因素为巨噬细胞浸润及其所诱发的M1亚型转化和血管新生。我们也在该子代肥胖雌鼠的脂肪组织中发现巨噬细胞明显向M1亚型转化，故推测宫内高雄可诱导巨噬细胞浸润和向M1亚型转化及血管新生，引起子代脂肪组织重塑及肥胖。本研究拟先构建两种子代雌鼠模型：①脂肪示踪转基因小鼠②脂质体去除巨噬细胞后的新生SD大鼠，分别探讨宫内高雄环境下巨噬细胞浸润对脂肪组织重塑及相关分子表达的影响；再建立巨噬细胞-脂肪细胞、巨噬细胞-内皮细胞两种细胞共培养体系，进一步探讨高雄状态下巨噬细胞的作用及相关分子机制。本研究可为早期阻遏PCOS子代肥胖提供重要理论依据。