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

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, addi...

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Bibliographic Details
Published in:Molecular human reproduction 2019-05, Vol.25 (5), p.257-264
Main Authors: Gómez-Elías, Matías D, May, María, Munuce, María José, Bahamondes, Luis, Cuasnicú, Patricia S, Cohen, Débora J
Format: Article
Language:English
Subjects:
Animals
Contraception, Postcoital - methods
Contraceptive Agents, Hormonal - pharmacology
Copulation - physiology
Drug Administration Schedule
Drug Evaluation, Preclinical
Embryo Implantation - drug effects
Embryo Implantation - physiology
Embryonic Development - drug effects
Embryonic Development - physiology
Female
Fertilization - physiology
Humans
Male
Mice
Norpregnadienes - pharmacology
Ovary - drug effects
Ovary - physiology
Ovulation - physiology
Pregnancy
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Summary: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.
ISSN:1460-2407
1460-2407
DOI:10.1093/molehr/gaz013