血根碱通过凋亡过程对小鼠卵母细胞成熟、受精及胎儿发育的有害影响。
Hazardous effects of sanguinarine on maturation of mouse oocytes, fertilization, and fetal development through apoptotic processes.
作者信息
Chan Wen-Hsiung
机构信息
Department of Bioscience Technology and Center for Nanotechnology, Chung Yuan Christian University, Chung Li, Taiwan.
Center for Biomedical Technology, Chung Yuan Christian University, Chung Li, Taiwan.
出版信息
Environ Toxicol. 2015 Jul 8;30(8):946-55. doi: 10.1002/tox.21969. Epub 2014 Feb 21.
Previously, we reported that sanguinarine, a phytoalexin with antimicrobial, anti-oxidant, anti-inflammatory and pro-apoptotic effects, is a risk factor for normal embryonic development that triggers apoptotic processes in the inner cell mass of mouse blastocysts, causing decreased embryonic development and cell viability. In the current study, we investigated the deleterious effects of sanguinarine on mouse oocyte maturation, in vitro fertilization (IVF), and subsequent pre- and postimplantation development both in vitro and in vivo. Notably, sanguinarine significantly impaired mouse oocyte maturation, decreased IVF rates, and inhibited subsequent embryonic development in vitro. Preincubation of oocytes with sanguinarine during in vitro maturation induced an increase in postimplantation embryo resorption and a decrease in mouse fetal weight. In an in vivo animal model, 1 to 5 μM sanguinarine, provided in drinking water, caused a decrease in oocyte maturation and IVF, and led to deleterious effects on early embryonic development. Importantly, preincubation of oocytes with a caspase-3-specific inhibitor effectively blocked sanguinarine-triggered deleterious effects, clearly implying that embryonic injury induced by sanguinarine is mediated by a caspase-dependent apoptotic mechanism.
此前,我们报道过血根碱,一种具有抗菌、抗氧化、抗炎和促凋亡作用的植保素,是正常胚胎发育的一个风险因素,它会触发小鼠囊胚内细胞团的凋亡过程,导致胚胎发育和细胞活力下降。在当前研究中,我们调查了血根碱对小鼠卵母细胞成熟、体外受精(IVF)以及随后体外和体内植入前和植入后发育的有害影响。值得注意的是,血根碱显著损害小鼠卵母细胞成熟,降低体外受精率,并抑制随后的体外胚胎发育。在体外成熟过程中用血根碱对卵母细胞进行预孵育,会导致植入后胚胎吸收增加和小鼠胎儿体重下降。在体内动物模型中,饮用水中提供1至5μM血根碱会导致卵母细胞成熟和体外受精率降低,并对早期胚胎发育产生有害影响。重要的是,用半胱天冬酶-3特异性抑制剂对卵母细胞进行预孵育可有效阻断血根碱引发的有害影响,这清楚地表明血根碱诱导的胚胎损伤是由半胱天冬酶依赖性凋亡机制介导的。