Department of Medical Genetics, China Medical University, Shenyang, China.
Department of Obstetrics and Gynecology, Shengjing Hospital, China Medical University, Shenyang, 110004, China; Medical Research Center of Shengjing Hospital, China Medical University, Shenyang, 110004, China; Key Laboratory of Research and Application of Animal Model for Environmental and Metabolic Diseases, Liaoning Province, China.
Toxicol Lett. 2021 Jul 1;345:54-60. doi: 10.1016/j.toxlet.2021.04.014. Epub 2021 Apr 16.
Congenital clubfoot (CCF) is a common birth defect. Maternal smoking during pregnancy increases the risk of CCF. In previous research, we found muscle phenotypes similar to CCF in four and a half LIM domain protein 1 (FHLI) offspring mice (FHL1). However, the role of P2RX7-mediated pyroptosis in the effect of cigarette smoke (CS) on the skeletal muscle of FHL1 mice during pregnancy is unclear. In the present study, pregnant mice at 11 days of gestation were exposed to CS and male offspring of wild-type (WT) and FHL1 mice were divided into four groups (Control-WT, Control-KO, CS-WT, CS-KO). The histomorphology of lower limb muscles was examined using hematoxylin and eosin (H&E) staining. P2RX7, indicators of pyroptosis (NLRP3, ASC, cleaved-caspase 1, IL-1β), and cytoskeletal proteins (MYBPC2, LDB3) were also detected using immunoblotting. CS exposure during pregnancy aggravated the muscle phenotype similar to CCF in FHL1 offspring mice. FHL1 gene knockout (KO) or CS exposure during pregnancy each activated the expression of P2RX7, cell pyroptosis-related proteins (NLRP3, ASC, cleaved-caspase 1, IL-1β), a muscle injury marker (MYOD1), and cytoskeletal proteins (MYBPC2, LDB3); these two factors had an additive effect. The results showed maternal smoking during pregnancy aggravated muscle phenotype similar to CCF in FHL1 offspring mice through P2RX7-mediated pyroptosis.
先天性马蹄内翻足（CCF）是一种常见的出生缺陷。母亲在怀孕期间吸烟会增加 CCF 的风险。在之前的研究中，我们在四个半 LIM 结构域蛋白 1（FHLI）后代小鼠（FHL1）中发现了与 CCF 相似的肌肉表型。然而，细胞焦亡在香烟烟雾（CS）对妊娠 FHL1 小鼠骨骼肌影响中的作用尚不清楚。在本研究中，在妊娠 11 天的孕鼠暴露于 CS 中，野生型（WT）和 FHL1 小鼠的雄性后代分为四组（Control-WT、Control-KO、CS-WT、CS-KO）。使用苏木精和伊红（H&E）染色检查下肢肌肉的组织形态。使用免疫印迹法检测 P2RX7、细胞焦亡（NLRP3、ASC、裂解型半胱天冬酶 1、IL-1β）和细胞骨架蛋白（MYBPC2、LDB3）的指标。妊娠期间 CS 暴露加重了 FHL1 后代小鼠类似 CCF 的肌肉表型。FHL1 基因敲除（KO）或妊娠期间 CS 暴露均激活了 P2RX7、细胞焦亡相关蛋白（NLRP3、ASC、裂解型半胱天冬酶 1、IL-1β）、肌肉损伤标志物（MYOD1）和细胞骨架蛋白（MYBPC2、LDB3）的表达；这两个因素具有相加作用。结果表明，母亲在怀孕期间吸烟通过 P2RX7 介导的细胞焦亡加重了 FHL1 后代小鼠类似 CCF 的肌肉表型。
