Nicotine exposure is a common adverse environment during pregnancy and causes developmental toxicity of long bones in offspring. However, the effect of prenatal nicotine exposure (PNE) on bone mass accumulation in female offspring and its mechanism remained to be further investigated. In this study, we constructed a PNE rat model and collected the long bone and the bone marrow mesenchymal stem cells (BMSCs) from female offspring rats for the detection of bone mass, cell apoptosis, and the expressions of osteogenesis‐ and apoptosis‐related genes. The results revealed that PNE induced low bone mass in female offspring rats and was associated with the suppression of osteogenic function. Moreover, the apoptosis of BMSCs derived from the PNE female offspring rats was raised, and the expression ratio of apoptosis marker genes BAX/BCL‐2 was significantly increased. Further, PNE inhibited the expression and function of insulin‐like growth factor l (IGF1) signaling pathway in BMSCs. However, the exogenous IGF1 treatment partially ameliorated the increased apoptosis of BMSCs derived from the PNE female offspring rats. In conclusion, PNE induced low bone mass in female offspring rats, which was attributed to the increased apoptosis of BMSCs due to functional inhibition of IGF1 signaling pathway.

中文翻译：

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间充质干细胞凋亡增加通过 IGF1 通路介导雌性后代大鼠产前尼古丁暴露引起的骨质减少


尼古丁暴露是怀孕期间常见的不良环境，会导致后代长骨发育毒性。然而，产前尼古丁暴露 （PNE） 对女性后代骨量积累的影响及其机制仍有待进一步研究。在本研究中，我们构建了 PNE 大鼠模型，并收集了雌性后代大鼠的长骨和骨髓间充质干细胞 （BMSC），用于检测骨量、细胞凋亡以及成骨和细胞凋亡相关基因的表达。结果显示，PNE 诱导雌性后代大鼠骨量低，并与成骨功能的抑制有关。此外，PNE 雌性后代大鼠来源的 BMSCs 凋亡水平升高，凋亡标志基因 BAX/BCL-2 的表达比显着增加。此外，PNE 抑制 BMSC 中胰岛素样生长因子 l （IGF1） 信号通路的表达和功能。然而，外源性 IGF1 处理部分改善了 PNE 雌性后代大鼠来源的 BMSCs 细胞凋亡增加。综上所述，PNE 诱导雌性后代大鼠骨量低，这归因于 IGF1 信号通路的功能抑制导致 BMSCs 凋亡增加。