Maternal stressors during the prenatal and perinatal periods are associated with increased susceptibility for and severity of chronic disease phenotypes in adult offspring. In this study, we used a rat model of maternal high-fat diet (HFD) exposure during pregnancy and lactation to investigate the impact on skeletal homeostasis in offspring. In the distal femur, young male and female offspring (up to 3 weeks of age) from dams fed a HFD exhibited marked increases in trabecular bone volume relative to offspring from dams fed a chow diet, but this was followed by sustained bone loss. By 15 weeks of age, male offspring of HFD fed dams exhibited a 33% reduction in trabecular bone volume fraction that histomorphometric analyses revealed was due to a nearly threefold increase in the abundance of bone-resorbing osteoclasts, while there were no differences between female control and HFD offspring by 15 weeks of age. The osteoblastic differentiation of male offspring-derived bone marrow stromal cells was not affected by maternal diet. However, osteoclastic precursors isolated from the male offspring of HFD fed dams exhibited enhanced differentiation in vitro, forming larger osteoclasts with higher expression of the fusion marker DC-STAMP. This effect appears to be mediated by a cell autonomous increase in the sensitivity of precursors to RANKL. Taken together, these results suggest that maternal stressors like HFD exposure have persistent consequences for the skeletal health of offspring that may ultimately lead to a predisposition for osteopenia/osteoporosis.

产前和围产期的母亲压力源与成年后代慢性疾病表型的易感性和严重性增加有关。在这项研究中，我们使用了孕期和哺乳期母体高脂饮食 (HFD) 暴露的大鼠模型来研究对后代骨骼稳态的影响。在股骨远端，喂食 HFD 的水坝的年轻雄性和雌性后代（最多 3 周龄）与喂食食物的水坝的后代相比，表现出骨小梁体积显着增加，但随后出现持续的骨质流失。到 15 周龄时，HFD 喂养的水坝的雄性后代表现出 33% 的骨小梁体积分数减少，组织形态学分析显示这是由于骨吸收破骨细胞的丰度增加了近三倍，而在 15 周龄时，雌性对照和 HFD 后代之间没有差异。雄性后代来源的骨髓基质细胞的成骨细胞分化不受母体饮食的影响。然而，从喂食 HFD 的水坝的雄性后代中分离出的破骨细胞前体在体外表现出增强的分化，形成更大的破骨细胞，融合标记物 DC-STAMP 的表达更高。这种效应似乎是由前体对 RANKL 敏感性的细胞自主增加所介导的。总之，这些结果表明，母体压力源（如 HFD 暴露）会对后代的骨骼健康产生持续影响，最终可能导致骨质减少/骨质疏松症的易感性。雄性后代来源的骨髓基质细胞的成骨细胞分化不受母体饮食的影响。然而，从喂食 HFD 的水坝的雄性后代中分离出的破骨细胞前体在体外表现出增强的分化，形成更大的破骨细胞，融合标记物 DC-STAMP 的表达更高。这种效应似乎是由前体对 RANKL 敏感性的细胞自主增加所介导的。总之，这些结果表明，母体压力源（如 HFD 暴露）会对后代的骨骼健康产生持续影响，最终可能导致骨质减少/骨质疏松症的易感性。雄性后代来源的骨髓基质细胞的成骨细胞分化不受母体饮食的影响。然而，从喂食 HFD 的水坝的雄性后代中分离出的破骨细胞前体在体外表现出增强的分化，形成更大的破骨细胞，融合标记物 DC-STAMP 的表达更高。这种效应似乎是由前体对 RANKL 敏感性的细胞自主增加所介导的。总之，这些结果表明，母体压力源（如 HFD 暴露）会对后代的骨骼健康产生持续影响，最终可能导致骨质减少/骨质疏松症的易感性。形成更大的破骨细胞，融合标记物 DC-STAMP 的表达更高。这种效应似乎是由前体对 RANKL 敏感性的细胞自主增加所介导的。总之，这些结果表明，母体压力源（如 HFD 暴露）会对后代的骨骼健康产生持续影响，最终可能导致骨质减少/骨质疏松症的易感性。形成更大的破骨细胞，融合标记物 DC-STAMP 的表达更高。这种效应似乎是由前体对 RANKL 敏感性的细胞自主增加所介导的。总之，这些结果表明，母体压力源（如 HFD 暴露）会对后代的骨骼健康产生持续影响，最终可能导致骨质减少/骨质疏松症的易感性。