A single post-ovulatory dose of ulipristal acetate impairs post-fertilization events in mice.


Journal

Molecular human reproduction
ISSN: 1460-2407
Titre abrégé: Mol Hum Reprod
Pays: England
ID NLM: 9513710

Informations de publication

Date de publication:
01 05 2019
Historique:
received: 07 11 2018
revised: 30 01 2019
accepted: 26 02 2019
pubmed: 3 3 2019
medline: 23 5 2020
entrez: 3 3 2019
Statut: ppublish

Résumé

Ulipristal acetate (UPA) is a selective progesterone receptor modulator used for emergency contraception that has proven to be highly effective in preventing pregnancy when taken up to 120 h after unprotected sexual intercourse. Even though it may act mainly by delaying or inhibiting ovulation, additional effects of UPA on post-fertilization events cannot be excluded. Therefore, the aim of this study was to determine whether a single post-ovulatory dose of UPA could prevent pregnancy using the mouse as a pre-clinical model. Mated females received a single dose of UPA (40 mg/kg) on Day E1.5 or E2.5 (E0.5: copulatory plug detection) and post-fertilization events were evaluated. Our studies revealed that UPA administration produced a significant decrease in the number of conceptuses compared to control. Moreover, UPA-treated females exhibited a lower number of early implantation sites on Day E5.5, despite normal in vivo embryo development and transport to the uterus at E3.5. Administration of UPA produced histological and functional alterations in the uterine horns, i.e., a dyssynchronous growth between endometrial glands and stroma, with non-physiological combination of both fractions compared to controls, and a completely impaired ability to respond to an artificial decidualization stimulus. Altogether, our results show that the administration of a single post-ovulatory dose of UPA impairs mouse pregnancy probably due to an effect on embryo-uterine interaction, supporting additional effects of the drug on post-fertilization events. Although these studies cannot be performed with human samples, our results with the mouse model provide new insights into the mechanism of action of UPA as an emergency contraception method.

Identifiants

pubmed: 30824928
pii: 5368326
doi: 10.1093/molehr/gaz013
doi:

Substances chimiques

Contraceptive Agents, Hormonal 0
Norpregnadienes 0
ulipristal acetate YF7V70N02B

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

257-264

Informations de copyright

© The Author 2019. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Auteurs

Matías D Gómez-Elías (MD)

Instituto de Biología y Medicina Experimental (IBYME-CONICET), Buenos Aires, Argentina.

María May (M)

Instituto de Investigaciones Farmacológicas (ININFA-UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.

María José Munuce (MJ)

Laboratory of Reproductive Medicine, Biochemical Chemistry Area, School of Biochemical and Pharmaceutical Sciences, National University of Rosario, Rosario, Argentina.

Luis Bahamondes (L)

Department of Obstetrics and Gynaecology, School of Medicine, University of Campinas (UNICAMP), Campinas, Brazil.

Patricia S Cuasnicú (PS)

Instituto de Biología y Medicina Experimental (IBYME-CONICET), Buenos Aires, Argentina.

Débora J Cohen (DJ)

Instituto de Biología y Medicina Experimental (IBYME-CONICET), Buenos Aires, Argentina.

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Classifications MeSH