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High-Throughput In Vitro Screening Identified Nemadipine as a Novel Suppressor of Embryo Implantation.
Chen, Xian; Fernando, Sudini Ranshaya; Lee, Yin-Lau; Yeung, William Shu-Biu; Ng, Ernest Hung-Yu; Li, Raymond Hang-Wun; Lee, Kai-Fai.
Afiliación
  • Chen X; Department of Obstetrics and Gynaecology, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
  • Fernando SR; Department of Obstetrics and Gynaecology, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
  • Lee YL; Department of Animal Science, Faculty of Animal Science and Export Agriculture, Uva Wellassa University, Badulla 90000, Sri Lanka.
  • Yeung WS; Department of Obstetrics and Gynaecology, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
  • Ng EH; Shenzhen Key Laboratory of Fertility Regulation, The University of Hong Kong-Shenzhen Hospital, Shenzhen 518000, China.
  • Li RH; Department of Obstetrics and Gynaecology, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
  • Lee KF; Shenzhen Key Laboratory of Fertility Regulation, The University of Hong Kong-Shenzhen Hospital, Shenzhen 518000, China.
Int J Mol Sci ; 23(9)2022 May 03.
Article en En | MEDLINE | ID: mdl-35563464
Current contraceptive methods interfere with folliculogenesis, fertilization, and embryo implantation by physical or hormonal approaches. Although hormonal contraceptive pills are effective in regulating egg formation, they are less effective in preventing embryo implantation. To explore the use of non-hormonal compounds that suppress embryo implantation, we established a high-throughput spheroid-endometrial epithelial cell co-culture assay to screen the Library of Pharmacologically Active Compounds (LOPAC) for compounds that affect trophoblastic spheroid (blastocyst surrogate) attachment onto endometrial epithelial Ishikawa cells. We identified 174 out of 1280 LOPAC that significantly suppressed BeWo spheroid attachment onto endometrial Ishikawa cells. Among the top 20 compounds, we found the one with the lowest cytotoxicity in Ishikawa cells, P11B5, which was later identified as Nemadipine-A. Nemadipine-A at 10 µM also suppressed BeWo spheroid attachment onto endometrial epithelial RL95-2 cells and primary human endometrial epithelial cells (hEECs) isolated from LH +7/8-day endometrial biopsies. Mice at 1.5 days post coitum (dpc) treated with a transcervical injection of 100 µg/kg Nemadipine-A or 500 µg/kg PRI-724 (control, Wnt-inhibitor), but not 10 µg/kg Nemadipine-A, suppressed embryo implantation compared with controls. The transcript expressions of endometrial receptivity markers, integrin αV (ITGAV) and mucin 1 (MUC1), but not ß-catenin (CTNNB1), were significantly decreased at 2.5 dpc in the uterus of treated mice compared with controls. The reduction of embryo implantation by Nemadipine-A was likely mediated through suppressing endometrial receptivity molecules ITGAV and MUC1. Nemadipine-A is a potential novel non-hormonal compound for contraception.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Implantación del Embrión / Endometrio Tipo de estudio: Diagnostic_studies / Screening_studies Límite: Animals Idioma: En Revista: Int J Mol Sci Año: 2022 Tipo del documento: Article País de afiliación: China Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Implantación del Embrión / Endometrio Tipo de estudio: Diagnostic_studies / Screening_studies Límite: Animals Idioma: En Revista: Int J Mol Sci Año: 2022 Tipo del documento: Article País de afiliación: China Pais de publicación: Suiza