Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, China.
Department of Pharmacy, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China; Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071, China.
Reprod Toxicol. 2023 Jun;118:108366. doi: 10.1016/j.reprotox.2023.108366. Epub 2023 Mar 22.
Corn oil, sodium carboxymethyl cellulose (CMC-Na), and dimethyl sulfoxide (DMSO) are widely used as solvents or suspensions in animal experiments, but the effects of prenatal exposure to them on fetal development have not been reported. In this study, Kunming mice were given a conventional dose of corn oil (9.2 g/kg·d), CMC-Na (0.05 g/kg·d) or DMSO (0.088 g/kg·d) during gestation days 10-18, and the pregnancy outcome, fetal physical development, serum phenotype, and multi-organ function changes were observed. The results showed that corn oil decreased serum triglyceride level in males but increased their serum testosterone and CORT levels, and affected female placenta and female/male multi-organ functions (mainly bone, liver, kidney). CMC-Na increased female/male body lengths and tail lengths, decreased serum glucose and total cholesterol levels in males as well as increased their serum LDL-C/HDL-C ratio and testosterone level, decreased female serum bile acid level, and affected male/female placenta and multi-organ functions (mainly bone, liver, hippocampus). DMSO decreased male body weight and serum glucose level, decreased male/female serum bile acid levels, and affected male/female placenta and multi-organs functions (mainly bone, hippocampus, adrenal gland). In conclusion, prenatal exposure to a conventional dose of corn oil, CMC-Na or DMSO could affect fetal physical development and multi-organ functions, and has the characteristics of "multi-pathway, multi-organ and multi-target". This study provides the experimental basis for the rational selection of solvents or suspensions in pharmacology and toxicology studies.
玉米油、羧甲基纤维素钠(CMC-Na)和二甲基亚砜(DMSO)广泛用作动物实验中的溶剂或悬浮剂,但它们在产前暴露对胎儿发育的影响尚未报道。在这项研究中,昆明小鼠在妊娠第 10-18 天给予常规剂量的玉米油(9.2g/kg·d)、CMC-Na(0.05g/kg·d)或 DMSO(0.088g/kg·d),观察妊娠结局、胎儿体格发育、血清表型和多器官功能变化。结果表明,玉米油降低了雄性血清甘油三酯水平,但增加了其血清睾酮和 CORT 水平,并影响了雌性胎盘和雌性/雄性多器官功能(主要是骨骼、肝脏、肾脏)。CMC-Na 增加了雌雄体长和尾长,降低了雄性血清葡萄糖和总胆固醇水平,增加了其血清 LDL-C/HDL-C 比值和睾酮水平,降低了雌性血清胆汁酸水平,并影响了雌雄胎盘和多器官功能(主要是骨骼、肝脏、海马体)。DMSO 降低了雄性体重和血清葡萄糖水平,降低了雌雄血清胆汁酸水平,并影响了雌雄胎盘和多器官功能(主要是骨骼、海马体、肾上腺)。总之,产前暴露于常规剂量的玉米油、CMC-Na 或 DMSO 可影响胎儿体格发育和多器官功能,具有“多途径、多器官、多靶点”的特点。本研究为药理学和毒理学研究中溶剂或悬浮剂的合理选择提供了实验依据。