A single post-ovulatory dose of ulipristal acetate impairs post-fertilization events in mice.
Animals
Contraception, Postcoital
/ methods
Contraceptive Agents, Hormonal
/ pharmacology
Copulation
/ physiology
Drug Administration Schedule
Drug Evaluation, Preclinical
Embryo Implantation
/ drug effects
Embryonic Development
/ drug effects
Female
Fertilization
/ physiology
Humans
Male
Mice
Norpregnadienes
/ pharmacology
Ovary
/ drug effects
Ovulation
/ physiology
Pregnancy
decidualization
embryo transport
emergency contraception
implantation
ulipristal acetate
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
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
257-264Informations 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.