Construction of a drug screening model for miscarriage from induced pluripotent stem cells in vitro
10.16438/j.0513-4870.2020-1508
- VernacularTitle:利用诱导多能干细胞构建流产毒性药物的体外筛查模型
- Author:
Shan-shan WU
1
;
Wen-juan FAN
2
;
Rui-ling LI
3
;
Yan-li WANG
4
;
Pei-quan LI
4
;
Chao-jie LI
4
;
Jin-bo DENG
4
Author Information
1. National Health Commission Key Laboratory of Birth Defects Prevention, Henan Key Laboratory of Population Defects Prevention, Henan Institute of Reproduction Health Science and Technology, Zhengzhou 450002, China; School of Nursing and Health, Henan University, Kaifeng 475000, China
2. Luohe Medical College, Luohe 462002, China
3. School of Nursing and Health, Henan University, Kaifeng 475000, China
4. National Health Commission Key Laboratory of Birth Defects Prevention, Henan Key Laboratory of Population Defects Prevention, Henan Institute of Reproduction Health Science and Technology, Zhengzhou 450002, China
- Publication Type:Research Article
- Keywords:
induced pluripotent stem cell;
reproductive and developmental toxicity;
model establishment;
rug screening
- From:
Acta Pharmaceutica Sinica
2021;56(2):503-510
- CountryChina
- Language:Chinese
-
Abstract:
Drug use during pregnancy is unavoidable. Therefore, it is vitally important for medical workers to help pregnant women take drugs correctly to reduce the incidence of spontaneous abortion, premature birth, and low birth weight. In our study, drug screening model with induced pluripotent stem cells (iPSCs) was used to find some improper drugs which will result in woman's abortion. With 3D culture in vitro, iPSCs can form embryoid bodies (EBs) and cerebral organoids, which simulated in vitro development of early embryos, from inner cell mass to germ-layer differentiation. In the experiment, EBs were exposed to mifepristone (RU486), and three experimental groups were divided randomly. They were control group (without RU486), low-dose group (L-RU486, 10 μg·mL-1), and high-dose group (H-RU486, 20 μg·mL-1). After mifepristone exposure, EBs were observed at days 5, 8, and 11, including size of EB, cell apoptosis, and differentiation of germ layers, by using inverted optical microscope, TUNEL assay, and immunofluorescent staining. The results showed that through 3D culture, iPSCs could develop into embryoid bodies, neural rosettes, and finally cerebral organoids. After mifepristone exposure, EBs' sizes were decreased (P < 0.01); the levels of cell apoptosis in EBs were increased after mifepristone exposure (P < 0.01); the development of EBs' germ layer was affected. Mifepristone exposure could inhibit the proliferation of embryonic stem cells, reduce the differentiation of ectoderm (P < 0.01) and promote the development of mesoderm (P < 0.05). In conclusion, iPSCs can be used as a screening model for abortion drug, and EBs’ diameter, cell apoptosis, and differentiation changes of the germ layers can serve as criteria of abortion drug screening.
