Wang Zilin, Liu Wenduo, Sim Hyun-Jaung, Lee Jeong-Chae, Kook Sung-Ho, Kim Sang Hyun
Department of Sports Science, College of Natural Science, Jeonbuk National University, Jeonju, Republic of Korea.
Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences and School of Dentistry, Jeonbuk National University, Jeonju, Republic of Korea.
J Cachexia Sarcopenia Muscle. 2025 Oct;16(5):e70047. doi: 10.1002/jcsm.70047.
Fine particulate matter has developmental toxicity, and midgestation is an important period for the development of foetal skeletal muscle. The ability of exercise to modulate skeletal muscle damage in mice exposed to PM during gestation remains unclear.
Pregnant C57BL/6 mice were exposed to 50 μg/m PM for 2 h on five consecutive days starting at embryonic day 12.5 (E12.5d). Combined exercise (treadmill endurance training and weighted ladder resistance training) was followed for 8 weeks in the 4-week-old offspring to verify the regulatory effect of exercise.
Offspring exposed to PM during gestation showed lower body weight (male, -44.3%; female, -44.8%; p < 0.001), lower skeletal muscle mass (male: TA fibre size, -42%, p < 0.001; TA mass, -37%, p < 0.01; gastrocnemius mass, -46.5%, p < 0.001; female: TA fibre size, -51.6%, p < 0.001; TA mass, -29.8%, p < 0.05; gastrocnemius mass, -40.7%, p < 0.01) and mitochondrial (size decreased for TEM; male: PGC-1α, +78.1%, p < 0.05; Tfam, +591.3%, p < 0.001; FIS-1, +627%, p < 0.001; female: Tfam, +452%, p < 0.01; FIS-1, +345.6%, p < 0.01) dysfunction (at 4 weeks old). They also showed catch-up growth (between 3 and 8 weeks of age; male average weight gain level, +57.9%, p < 0.01; female average weight gain level, +66%, p < 0.05), although they still showed significant mitochondrial damage and impaired glucose metabolism (at 13 weeks of age; male: mitochondrial damage for TEM; Tfam, -46%, p < 0.01; PINK-1, -33.8%, p < 0.05; Parkin, -62%, p < 0.01; PFK-1, -17%, p < 0.05; female: mitochondrial damage for TEM; PFK-1, -28.7%, p < 0.01). Combined exercise was unable to regulate the skeletal muscle system disorder that occurred in male offspring exposed to PM during pregnancy. However, it activated the mitophagy (PINK-1, +94.6%, p < 0.05; Parkin, +90.2%, p < 0.001) in female offspring exposed to PM during pregnancy, thereby improving mitochondrial damage.
Combined exercise had bidirectional, sex-specific effects: Male offspring exhibited reduced responsiveness to exercise, with persistent mitochondrial damage, whereas female offspring showed improved mitochondrial health through increased mitophagy flux.
细颗粒物具有发育毒性，而妊娠中期是胎儿骨骼肌发育的重要时期。运动对妊娠期暴露于细颗粒物的小鼠骨骼肌损伤的调节能力尚不清楚。
从胚胎第12.5天（E12.5d）开始，将怀孕的C57BL/6小鼠连续5天每天暴露于50μg/m³的细颗粒物中2小时。在4周龄的后代中进行8周的联合运动（跑步机耐力训练和负重阶梯阻力训练），以验证运动的调节作用。
妊娠期暴露于细颗粒物的后代在4周龄时体重较低（雄性，-44.3%；雌性，-44.8%；p<0.001），骨骼肌质量较低（雄性：胫前肌纤维大小，-42%，p<0.001；胫前肌质量，-37%，p<0.01；腓肠肌质量，-46.5%，p<0.001；雌性：胫前肌纤维大小，-51.6%，p<0.001；胫前肌质量，-29.8%，p< 0.05；腓肠肌质量，-40.7%，p<0.01），线粒体功能障碍（透射电镜显示大小减小；雄性：PGC-1α，+78.1%，p<0.05；Tfam，+591.3%，p<0.001；FIS-1，+627%，p<0.001；雌性：Tfam，+452%，p<0.01；FIS-1，+345.6%，p<0.01）。它们还表现出追赶生长（3至8周龄之间；雄性平均体重增加水平，+57.9%，p<0.01；雌性平均体重增加水平，+66%，p<0.05），尽管在13周龄时它们仍表现出明显的线粒体损伤和葡萄糖代谢受损（雄性：透射电镜显示线粒体损伤；Tfam，-46%，p<0.01；PINK-1，-33.8%，p<0.05；Parkin，-62%，p<0.01；PFK-1，-（此处原文可能有误，推测应为 -17%），p<0.05；雌性：透射电镜显示线粒体损伤；PFK-1，-28.7% ，p<0.01）。联合运动无法调节妊娠期暴露于细颗粒物的雄性后代出现的骨骼肌系统紊乱。然而，它激活了妊娠期暴露于细颗粒物的雌性后代的线粒体自噬（PINK-1，+94.6%，p<0.05；Parkin，+90.2%，p<0.001），从而改善了线粒体损伤。
联合运动具有双向的、性别特异性的影响：雄性后代对运动的反应性降低，线粒体损伤持续存在，而雌性后代通过增加线粒体自噬通量改善了线粒体健康。
