Instituto de Biología y Medicina Experimental (IBYME-CONICET), Buenos Aires, Argentina.
Instituto de Investigaciones Farmacológicas (ININFA-UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
Mol Hum Reprod. 2019 May 1;25(5):257-264. doi: 10.1093/molehr/gaz013.
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.
醋酸乌利司他（UPA）是一种孕激素受体选择性调节剂，用于紧急避孕，已被证明在无保护性行为后 120 小时内服用时可有效防止怀孕。尽管它可能主要通过延迟或抑制排卵起作用，但不能排除 UPA 对受精后事件的其他影响。因此，本研究旨在确定单次排卵后给予 UPA 是否可以使用小鼠作为临床前模型来预防怀孕。交配后的雌性小鼠在 E1.5 或 E2.5 天（E0.5：交配栓检测）给予单次 UPA（40mg/kg）剂量，并评估受精后事件。我们的研究表明，与对照组相比，UPA 给药导致胚胎数量显著减少。此外，尽管 E3.5 时胚胎正常发育并运送到子宫，但 UPA 处理的雌性小鼠在 E5.5 时的早期着床部位数量较少。UPA 给药对子宫角产生了组织学和功能改变，即子宫内膜腺体和基质之间的生长不同步，与对照组相比，这两个部分的组合是非生理性的，并且完全丧失了对人工蜕膜化刺激的反应能力。总之，我们的结果表明，单次排卵后给予 UPA 剂量会损害小鼠怀孕，可能是因为它对胚胎-子宫相互作用的影响，支持该药物对受精后事件的其他影响。尽管这些研究不能用人样本来进行，但我们用小鼠模型得出的结果为 UPA 作为紧急避孕方法的作用机制提供了新的见解。
