Direct Effects of Mifepristone on Mice Embryogenesis: An In Vitro Evaluation by Single-Embryo RNA Sequencing Analysis
The clinical use of mifepristone for medical abortions has been established in 1987 in France and since 2000 in the United States. Mifepristone has a limited medical period that lasts <9 weeks of gestation, and the incidence of mifepristone treatment failure increases with gestation time. Mifepri...
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MDPI AG
2023-03-01
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| Online Access: | https://www.mdpi.com/2227-9059/11/3/907 |
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| author | Yu-Ting Su Jia-Shing Chen Kuo-Chung Lan Yung-Kuo Lee Tian-Huei Chu Yu-Cheng Ho Cheng-Chun Wu Fu-Jen Huang |
| author_facet | Yu-Ting Su Jia-Shing Chen Kuo-Chung Lan Yung-Kuo Lee Tian-Huei Chu Yu-Cheng Ho Cheng-Chun Wu Fu-Jen Huang |
| author_sort | Yu-Ting Su |
| collection | DOAJ |
| description | The clinical use of mifepristone for medical abortions has been established in 1987 in France and since 2000 in the United States. Mifepristone has a limited medical period that lasts <9 weeks of gestation, and the incidence of mifepristone treatment failure increases with gestation time. Mifepristone functions as an antagonist for progesterone and glucocorticoid receptors. Studies have confirmed that mifepristone treatments can directly contribute to endometrium disability by interfering with the endometrial receptivity of the embryo, thus causing decidual endometrial degeneration. However, whether mifepristone efficacy directly affects embryo survival and growth is still an open question. Some women choose to continue their pregnancy after mifepristone treatment fails, and some women express regret and seek medically unapproved mifepristone antagonization with high doses of progesterone. These unapproved treatments raise the potential risk of embryonic fatality and developmental anomalies. Accordingly, in the present study, we collected mouse blastocysts ex vivo and treated implanted blastocysts with mifepristone for 24 h. The embryos were further cultured to day 8 in vitro to finish their growth in the early somite stage, and the embryos were then collected for RNA sequencing (control <i>n</i> = 3, mifepristone <i>n</i> = 3). When we performed a gene set enrichment analysis, our data indicated that mifepristone treatment considerably altered the cellular pathways of embryos in terms of viability, proliferation, and development. The data indicated that mifepristone was involved in hallmark gene sets of protein secretion, mTORC1, fatty acid metabolism, IL-2-STAT5 signaling, adipogenesis, peroxisome, glycolysis, E2F targets, and heme metabolism. The data further revealed that mifepristone interfered with normal embryonic development. In sum, our data suggest that continuing a pregnancy after mifepristone treatment fails is inappropriate and infeasible. The results of our study reveal a high risk of fetus fatality and developmental problems when pregnancies are continued after mifepristone treatment fails. |
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| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-11T06:53:27Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
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| series | Biomedicines |
| spelling | doaj.art-48a5b916db764e42afa74dc9c504ba4f2023-11-17T09:47:22ZengMDPI AGBiomedicines2227-90592023-03-0111390710.3390/biomedicines11030907Direct Effects of Mifepristone on Mice Embryogenesis: An In Vitro Evaluation by Single-Embryo RNA Sequencing AnalysisYu-Ting Su0Jia-Shing Chen1Kuo-Chung Lan2Yung-Kuo Lee3Tian-Huei Chu4Yu-Cheng Ho5Cheng-Chun Wu6Fu-Jen Huang7Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung City 83301, TaiwanSchool of Medicine for International Students, College of Medicine, I-Shou University, Kaohsiung City 82425, TaiwanDepartment of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung City 83301, TaiwanMedical Laboratory, Medical Education and Research Center, Kaohsiung Armed Forces General Hospital, Kaohsiung City 80284, TaiwanMedical Laboratory, Medical Education and Research Center, Kaohsiung Armed Forces General Hospital, Kaohsiung City 80284, TaiwanSchool of Medicine, College of Medicine, I-Shou University, Kaohsiung City 82425, TaiwanSchool of Medicine, College of Medicine, I-Shou University, Kaohsiung City 82425, TaiwanDepartment of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung City 83301, TaiwanThe clinical use of mifepristone for medical abortions has been established in 1987 in France and since 2000 in the United States. Mifepristone has a limited medical period that lasts <9 weeks of gestation, and the incidence of mifepristone treatment failure increases with gestation time. Mifepristone functions as an antagonist for progesterone and glucocorticoid receptors. Studies have confirmed that mifepristone treatments can directly contribute to endometrium disability by interfering with the endometrial receptivity of the embryo, thus causing decidual endometrial degeneration. However, whether mifepristone efficacy directly affects embryo survival and growth is still an open question. Some women choose to continue their pregnancy after mifepristone treatment fails, and some women express regret and seek medically unapproved mifepristone antagonization with high doses of progesterone. These unapproved treatments raise the potential risk of embryonic fatality and developmental anomalies. Accordingly, in the present study, we collected mouse blastocysts ex vivo and treated implanted blastocysts with mifepristone for 24 h. The embryos were further cultured to day 8 in vitro to finish their growth in the early somite stage, and the embryos were then collected for RNA sequencing (control <i>n</i> = 3, mifepristone <i>n</i> = 3). When we performed a gene set enrichment analysis, our data indicated that mifepristone treatment considerably altered the cellular pathways of embryos in terms of viability, proliferation, and development. The data indicated that mifepristone was involved in hallmark gene sets of protein secretion, mTORC1, fatty acid metabolism, IL-2-STAT5 signaling, adipogenesis, peroxisome, glycolysis, E2F targets, and heme metabolism. The data further revealed that mifepristone interfered with normal embryonic development. In sum, our data suggest that continuing a pregnancy after mifepristone treatment fails is inappropriate and infeasible. The results of our study reveal a high risk of fetus fatality and developmental problems when pregnancies are continued after mifepristone treatment fails.https://www.mdpi.com/2227-9059/11/3/907mifepristoneRU-486abortionRNAseqembryoGSEA |
| spellingShingle | Yu-Ting Su Jia-Shing Chen Kuo-Chung Lan Yung-Kuo Lee Tian-Huei Chu Yu-Cheng Ho Cheng-Chun Wu Fu-Jen Huang Direct Effects of Mifepristone on Mice Embryogenesis: An In Vitro Evaluation by Single-Embryo RNA Sequencing Analysis Biomedicines mifepristone RU-486 abortion RNAseq embryo GSEA |
| title | Direct Effects of Mifepristone on Mice Embryogenesis: An In Vitro Evaluation by Single-Embryo RNA Sequencing Analysis |
| title_full | Direct Effects of Mifepristone on Mice Embryogenesis: An In Vitro Evaluation by Single-Embryo RNA Sequencing Analysis |
| title_fullStr | Direct Effects of Mifepristone on Mice Embryogenesis: An In Vitro Evaluation by Single-Embryo RNA Sequencing Analysis |
| title_full_unstemmed | Direct Effects of Mifepristone on Mice Embryogenesis: An In Vitro Evaluation by Single-Embryo RNA Sequencing Analysis |
| title_short | Direct Effects of Mifepristone on Mice Embryogenesis: An In Vitro Evaluation by Single-Embryo RNA Sequencing Analysis |
| title_sort | direct effects of mifepristone on mice embryogenesis an in vitro evaluation by single embryo rna sequencing analysis |
| topic | mifepristone RU-486 abortion RNAseq embryo GSEA |
| url | https://www.mdpi.com/2227-9059/11/3/907 |
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