Mifepristone Directly Disrupts Mouse Embryonic Development in Terms of Cellular Proliferation and Maturation In Vitro

Mifepristone (RU-486), a synthetic steroid with potent antiprogestogen and anti-glucocorticoid properties, has been widely used in clinical practice. Its effect on the endometrium, ovary, and fallopian tube has been well reported in many human and animal studies. However, its direct impact on post-i...

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Autores principales:	Yu-Ting Su, Jia-Shing Chen, Yi-Ru Tsai, Kuo-Chung Lan, Cheng-Chun Wu, Fu-Jen Huang
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	mifepristone endometrium embryo development progesterone abortion Chemical technology TP1-1185
Acceso en línea:	https://doaj.org/article/b05cd79638bb4b46be9213f591c91901
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spelling	oai:doaj.org-article:b05cd79638bb4b46be9213f591c919012021-11-25T19:08:10ZMifepristone Directly Disrupts Mouse Embryonic Development in Terms of Cellular Proliferation and Maturation In Vitro10.3390/toxics91102942305-6304https://doaj.org/article/b05cd79638bb4b46be9213f591c919012021-11-01T00:00:00Zhttps://www.mdpi.com/2305-6304/9/11/294https://doaj.org/toc/2305-6304Mifepristone (RU-486), a synthetic steroid with potent antiprogestogen and anti-glucocorticoid properties, has been widely used in clinical practice. Its effect on the endometrium, ovary, and fallopian tube has been well reported in many human and animal studies. However, its direct impact on post-implantation embryos remains underexplored. Additionally, some women choose to keep their pregnancy after mifepristone treatment fails. Thus, the potential risk remains controversial. Hence, this study investigated the direct effects of mifepristone on the development of mice blastocysts in vitro in terms of implantation and post-implantation. We detected the level of progesterone (P4) associated with ovulation in vivo. The presence of progesterone receptors (PRs) in blastocysts and post-implantation embryos was also evaluated. Cultured embryos were treated directly with mifepristone. We further examined embryonic implantation and post-implantation of blastocysts in vitro to evaluate the direct effects of mifepristone on embryos by the assessment of embryonic outgrowth and differential cell staining. In the oviduct lumen, the P4 level dramatically increased at 48 h and slightly decreased at 72 and 96 h following ovulation. PR was expressed in blastocysts not only in the preimplantation stage but also in the early post-implantation period. In the evaluation of developmental stages, mifepristone significantly reduced the successful ratio of developing into the late egg cylinder and the early somite stage. In addition, it further decreased the cell number of the embryos’ inner cell mass and trophectoderm. We herein provide evidence that mifepristone affects blastocyst viability directly and inhibits post-implantation embryo development in vitro. Furthermore, our data reveal a potential risk of fetus fatality and developmental problems when pregnancies are continued after mifepristone treatment fails.Yu-Ting SuJia-Shing ChenYi-Ru TsaiKuo-Chung LanCheng-Chun WuFu-Jen HuangMDPI AGarticlemifepristoneendometriumembryodevelopmentprogesteroneabortionChemical technologyTP1-1185ENToxics, Vol 9, Iss 294, p 294 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	mifepristone endometrium embryo development progesterone abortion Chemical technology TP1-1185
spellingShingle	mifepristone endometrium embryo development progesterone abortion Chemical technology TP1-1185 Yu-Ting Su Jia-Shing Chen Yi-Ru Tsai Kuo-Chung Lan Cheng-Chun Wu Fu-Jen Huang Mifepristone Directly Disrupts Mouse Embryonic Development in Terms of Cellular Proliferation and Maturation In Vitro
description	Mifepristone (RU-486), a synthetic steroid with potent antiprogestogen and anti-glucocorticoid properties, has been widely used in clinical practice. Its effect on the endometrium, ovary, and fallopian tube has been well reported in many human and animal studies. However, its direct impact on post-implantation embryos remains underexplored. Additionally, some women choose to keep their pregnancy after mifepristone treatment fails. Thus, the potential risk remains controversial. Hence, this study investigated the direct effects of mifepristone on the development of mice blastocysts in vitro in terms of implantation and post-implantation. We detected the level of progesterone (P4) associated with ovulation in vivo. The presence of progesterone receptors (PRs) in blastocysts and post-implantation embryos was also evaluated. Cultured embryos were treated directly with mifepristone. We further examined embryonic implantation and post-implantation of blastocysts in vitro to evaluate the direct effects of mifepristone on embryos by the assessment of embryonic outgrowth and differential cell staining. In the oviduct lumen, the P4 level dramatically increased at 48 h and slightly decreased at 72 and 96 h following ovulation. PR was expressed in blastocysts not only in the preimplantation stage but also in the early post-implantation period. In the evaluation of developmental stages, mifepristone significantly reduced the successful ratio of developing into the late egg cylinder and the early somite stage. In addition, it further decreased the cell number of the embryos’ inner cell mass and trophectoderm. We herein provide evidence that mifepristone affects blastocyst viability directly and inhibits post-implantation embryo development in vitro. Furthermore, our data reveal a potential risk of fetus fatality and developmental problems when pregnancies are continued after mifepristone treatment fails.
format	article
author	Yu-Ting Su Jia-Shing Chen Yi-Ru Tsai Kuo-Chung Lan Cheng-Chun Wu Fu-Jen Huang
author_facet	Yu-Ting Su Jia-Shing Chen Yi-Ru Tsai Kuo-Chung Lan Cheng-Chun Wu Fu-Jen Huang
author_sort	Yu-Ting Su
title	Mifepristone Directly Disrupts Mouse Embryonic Development in Terms of Cellular Proliferation and Maturation In Vitro
title_short	Mifepristone Directly Disrupts Mouse Embryonic Development in Terms of Cellular Proliferation and Maturation In Vitro
title_full	Mifepristone Directly Disrupts Mouse Embryonic Development in Terms of Cellular Proliferation and Maturation In Vitro
title_fullStr	Mifepristone Directly Disrupts Mouse Embryonic Development in Terms of Cellular Proliferation and Maturation In Vitro
title_full_unstemmed	Mifepristone Directly Disrupts Mouse Embryonic Development in Terms of Cellular Proliferation and Maturation In Vitro
title_sort	mifepristone directly disrupts mouse embryonic development in terms of cellular proliferation and maturation in vitro
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/b05cd79638bb4b46be9213f591c91901
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Mifepristone Directly Disrupts Mouse Embryonic Development in Terms of Cellular Proliferation and Maturation In Vitro

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